CA2103727A1 - Filler material for use in tissue welding - Google Patents
Filler material for use in tissue weldingInfo
- Publication number
- CA2103727A1 CA2103727A1 CA002103727A CA2103727A CA2103727A1 CA 2103727 A1 CA2103727 A1 CA 2103727A1 CA 002103727 A CA002103727 A CA 002103727A CA 2103727 A CA2103727 A CA 2103727A CA 2103727 A1 CA2103727 A1 CA 2103727A1
- Authority
- CA
- Canada
- Prior art keywords
- filler material
- tissue
- collagen
- energy
- biological tissue
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/00491—Surgical glue applicators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00365—Proteins; Polypeptides; Degradation products thereof
Abstract
A method of joining or reconstructing biological tissue such as a blood vessel (20) while providing a filler material like collagen (50) thereto; applying sutures (30A, 30B and 30C) on the incision; and denaturing the filler material and biological tissue with a laser (40) to cause joining of the filler material and biological tissue.
Description
WO92/14513 PCT/US92/011~
~ .~ , `! 2 1 0 3 7 2 7 FILLER MATERIAL FOR USE IN TISSUE WELDING
BACKGROUND OF THE INVENTION
Technical Field The present invention relates to the use of laser emitted optical energy or radio frequency ("RF") energy for joining, repairing or reconstructing biological tissue. In particular, the present invention relates to a method of utilizing a welding 10 rod filler material in combination with such optical or RF energy to join, repair or rebuild biological tissue.
Backqround Art Optical energy, in particular that generated by lasers, has been applied and utilized in the medical field for a variety of surgical purposes. The medical industry initially utilized industrial lasers for the destruction of tumors or surface lesions in patients.
20 At that time, the lasers were relatively crude, high powered and ineffective for delicate internal biological applications.
Subsequently, a variety of cauterization techniques were developed utilizing either laser or RF
25 techniques. Laser optical energy was also utilized to reduce the flow of blood in an open wound or in a surgically created incision: the optical energy being supplied in sufficient quantity to sear or burn the blood vessels thus sealing the open ends of the 30 capillaries and preventing blood flow. A typical use of laser cauterization is described in U.S. Patent 4,~22,853. Again, the types of lasers utilized at that time provided very high power application and very high wattage with the surrounding tissue also 35 being destroyed, thus causing longer healing times, infection and scarring.
.
- , WO92/14513 PCT/US92/011~
~, ,. j . .~; .
~ .~ , `! 2 1 0 3 7 2 7 FILLER MATERIAL FOR USE IN TISSUE WELDING
BACKGROUND OF THE INVENTION
Technical Field The present invention relates to the use of laser emitted optical energy or radio frequency ("RF") energy for joining, repairing or reconstructing biological tissue. In particular, the present invention relates to a method of utilizing a welding 10 rod filler material in combination with such optical or RF energy to join, repair or rebuild biological tissue.
Backqround Art Optical energy, in particular that generated by lasers, has been applied and utilized in the medical field for a variety of surgical purposes. The medical industry initially utilized industrial lasers for the destruction of tumors or surface lesions in patients.
20 At that time, the lasers were relatively crude, high powered and ineffective for delicate internal biological applications.
Subsequently, a variety of cauterization techniques were developed utilizing either laser or RF
25 techniques. Laser optical energy was also utilized to reduce the flow of blood in an open wound or in a surgically created incision: the optical energy being supplied in sufficient quantity to sear or burn the blood vessels thus sealing the open ends of the 30 capillaries and preventing blood flow. A typical use of laser cauterization is described in U.S. Patent 4,~22,853. Again, the types of lasers utilized at that time provided very high power application and very high wattage with the surrounding tissue also 35 being destroyed, thus causing longer healing times, infection and scarring.
.
- , WO92/14513 PCT/US92/011~
~, ,. j . .~; .
2 1 0 3 7 2 7 -- 2 -- t-., !
As newer, lower powered lasers were developed, techniques were developed for atheroma ablation or other endarterectomy procedures for blood vessels.
One such procedure is disclosed in U.S. Patent 5 4,878,492. The CO2, YAG and Excimer lasers all provided substantial improvements in these procedures due to their lower power output. These more sophisticated devices each provide better aiming of a narrower optical energy beam such that destruction of 10 the walls of the blood vessels can be minimized.
Also, advances in optical fiber technology allowed the surgeon to direct more accurately the optical energy to the desired location with greater precision.
Lasers have also been used to "glaze" the internal surfaces of blood vessels after balloon dilation and laser angioplasty in an attempt to prevent medical recollapse, intimal fibroplasia, and reobliteration.
Another procedure which has been developed 20 includes the use of optical energy for welding or otherwise joining or connecting biological tissue.
The original attempts to carry out these procedures began in the late 1960's and almost all universally met with failure not so much because of an inability 25 to weld or join the tissue together, but because of the weakness of the resulting weld. The use of the lower powered laser devices, either alone or in combination with physiologic solutions, however, allowed the surgeon to cool the weld site sufficiently 30 to obtain slight improvements in weld strength.
Furthermore, RF energy has recently been utilized in both uni- and bi-polar generators to attempt to "weld"
or "solder" biological tissue.
U.S. Patent 4,672,969 discloses one method and apparatus for utilizing laser emitted optical energy to effect wound closure or other reconstruction of biological tissue by applying the optical energy to -. . . . . . .. .
. ,, .. ., . ~ . ~.
As newer, lower powered lasers were developed, techniques were developed for atheroma ablation or other endarterectomy procedures for blood vessels.
One such procedure is disclosed in U.S. Patent 5 4,878,492. The CO2, YAG and Excimer lasers all provided substantial improvements in these procedures due to their lower power output. These more sophisticated devices each provide better aiming of a narrower optical energy beam such that destruction of 10 the walls of the blood vessels can be minimized.
Also, advances in optical fiber technology allowed the surgeon to direct more accurately the optical energy to the desired location with greater precision.
Lasers have also been used to "glaze" the internal surfaces of blood vessels after balloon dilation and laser angioplasty in an attempt to prevent medical recollapse, intimal fibroplasia, and reobliteration.
Another procedure which has been developed 20 includes the use of optical energy for welding or otherwise joining or connecting biological tissue.
The original attempts to carry out these procedures began in the late 1960's and almost all universally met with failure not so much because of an inability 25 to weld or join the tissue together, but because of the weakness of the resulting weld. The use of the lower powered laser devices, either alone or in combination with physiologic solutions, however, allowed the surgeon to cool the weld site sufficiently 30 to obtain slight improvements in weld strength.
Furthermore, RF energy has recently been utilized in both uni- and bi-polar generators to attempt to "weld"
or "solder" biological tissue.
U.S. Patent 4,672,969 discloses one method and apparatus for utilizing laser emitted optical energy to effect wound closure or other reconstruction of biological tissue by applying the optical energy to -. . . . . . .. .
. ,, .. ., . ~ . ~.
3 2 1 ~ 3 7 2 7 PCT/US92/011 ~, . .. .
produce thermal heating of the biological tissue to degree suitable for denaturing the tissue proteins such that the collagenous elements of the tissue form a "biological glue" which seals the tissue to effect 5 the joining. This glue is later reabsorbed by the body during the healing process. The patent discloses a number of different types of lasers with preference stated for the Nd:YAG type, because its particular wavelength allows optical energy to propagate without 10 substantial attenuation through water and/or blood for absorption in the tissue to be repaired.
Despite these improvements, however, the weakness of the weld joint still remains as the primary disadvantage of this procedure and extensive current research is being conducted in an attempt to improve on that deficiency. I have now invented a simple yet elegant welding procedure for biological tissue utilizing laser or RF energy which overcomes the shortcomings of the prior art.
SUMMARY OF THE INVENTION
The present invention relates to a method of joining or reconstructing biological tissue which comprises applying energy to the biological tissue 25 while providing a suitable filler material thereto;
denaturing or melting the filler material and adjacent biological tissue with the energy to cause mixing of the denatured or melted filler material and biological tissue, thus joining or reconstructing such tissue.
The filler material is preferably collagen and one embodiment of the inventive method includes adhesively attaching the collagen filler material to the biological tissue to assure proper placement thereupon. This may be achieved by applying the 35 collagen material adjacent the biological material with fibrin glue or other biological tissue adhesive.
, , , ,, . ..; ~
- .
' WO92/14513 ~ - PCT/US92/011~.
2103727 - 4 - f~
~_,f This method may also include applying an energy absorption aid to one of the filler materials or the biological tissue, or both, to facilitate absorption of the applied energy thereby. Generally, the energy 5 absorbing aid is applied to preselected locations prior to the application of energy thereto, and it also assists in visually determining the areas to be joined or reconstructed. Preferred energy absorbing aids include dyes, such as Vital Green or Basic Red, 10 blood or water.
Often, the biological tissue includes an incision and the method enables the surgeon to enclose the incision by the mixing and joining of the denatured or melted filler material and biological tissue. If 15 desired, spaced sutures may be placed in tissue surrounding the incision to fix the position of adjacent tissue.
The filler material may be prepared by dissolving a predetermined amount of collagen material in water 20 to form a solution, followed by drying or freeze drying of the solution in the desired form and shape of the collagen filler material. Preferably, the collagen material used to prepare the filler material is a mixture of an insoluble collagen material and a soluble collagen material in a weight ratio of about 1:3 to 3:1.
The present method also contemplates applying a physiologically acceptable solution to one of the collagen filler materials or the biological tissue to control the temperature of the joint due to the energy imparted thereto. The applied energy may be provided as optical energy (i.e., by a laser), from an RF
generator, or by an inert gas beam coagulator, since these devices have sufficient power dissipation to cause the energy or heat that they produce to be absorbed by the tissue and collagen filler material.
The heat provided by the coagulator or which is :, ~
:, ., `
..
.
WO92/14513 210 3 7 2 7 PCT/US92/011~
......
converted from the applied laser or RF energy) generally should be within a range bounded by the minimum absorption rate at which the protein elements of the tissue and collagen filler material are 5 converted to melted collagen and by a maximum absorption rate which would cause water in the tissue or collagen filler material to boil. The RF energy may be provided by uni- or bipolar techniques, since each will melt the collagen filler material into the 10 defect or joint area. Thus, the protein elements of the tissue and the collagen filler metal can be melted or denatured, mixed or combined, and then cooled to form a weld joint.
When the biological tissue includes a lesion, the method further comprises forming a seal of collagen material near or upon the lesion. When the lesion comprises at least two separated segments of biological tissue, the method further comprises placing the two segments of tissue in close proximity, 20 and guiding the energy source and collagen filler material into the area of their junction for joining or reconstruction thereof.
The features and advantages of the present invention are more readily understood when read in conjunction with the attached drawing figures wherein FIG. l is a perspective view of the use of a collagen 30 welding rod for closing an incision in a blood vessel with the use of a laser or bipolar RF electrode;
FIG. 2 is a detail of the denatured or melted collagen material in the weld joint of FIG. l;
FIG. 3 is a perspective view of the use of a 35 collagen strip in the laser joining of an incision;
and WO92/145]3 PCT/US92/011~
~lU~7~7: ~ I
FIG. 4 is a detail of denaturecl or melted collagen material being applied upon a tissue defect or lesion; and FIGS. 5-11 are photomicrographs which show the 5 morphology of various welded tissue joints.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
It is well known that biological tissue includes cell layers in a protein framework which provides 10 tensile strength. The proteins are amino acids, and it is known that the application of heat or optical energy can denature such proteins. When the source of heat or energy is removed, the proteins if not totally broken down cool and begin to reconfigure and form an 15 approximate replication of the prior tissue structure.
The prior art teaches that the application of either optical energy from a laser or RF energy from a suitable generator could be used to bring the temperature of the biological tissue above room 20 temperature but below the boiling point of water (preferably between 45-75F and more prefer 60-70~F).
The denaturing of collagen, a major source of protein in the human body, can also be achieved by the application of energy, and is believed to go into 25 solution and form a type of "biological glue" which seals the incision or discontinuity in the biological tissue. Thus, it is possible to seal lesions, anastomose a severed or incised vessel or to -~
reconstruct diseased or damaged tissue.
I have found that a major disadvantage of such laser welding procedures for rejoining incised tissue is that insufficient tissue material is present for completing a successful joint. When optical energy from the laser actually denatures or melts the tissue in the areas to be joined, a portion of the tissue thickness is reduced so that the denatured materials can flow towards each other and stic~; together to form . .
.
-, , - .. . .
. - - . , ~ . . , - , : , ..
, ~; - 7 -the joint. On relatively thin sections of tissue to be joined, such as in repairing an incised blood vessel wall, there is insufficient denatured material in the joint area for providing a sound, high tensile 5 strength connection.
Collagen is known for use in the medical field as a material for repairing tissue damage caused by thermal, chemical or mechanical trauma (see, e.g., "Collagen: Its Place In the Medical Industry" by J.M.
10 Pachence, et al., Medical Device and Diagnostic Industry, January, 1987). I have found that this material can be used as a filler which can be placed in the path of the laser beam, melted or denatured, and directed into the incision or the tissue which is to be reconstructed. Bipolar or unipolar RF energy will also yield the same or substantially similar results. Based on qualitative observations, the additional collagen molecules provided by the filler material allows the tensile strength of the welded 20 incision to be significantly increased.
The application of optical energy and the use of additional collagen material provides several advantages in addition to increased tensile strength.
The healing time of the wound is accelerated because 25 blood supply to the affected tissue can be reestablished immediately after the surgical procedure. In addition, little or no scarring is produced because sutures are eliminated or substantially minimized. Furthermore, the various 30 techniques disclosed herein enhance the accuracy of the welding procedure thus avoiding optical or RF
energy damage to adjacent or unintended areas of such tissl~e.
A wide variety of materials may be used as a 35 filler in this welding procedure. The most common source is collagen which may be obtained from bovine hides. Another material, which is ideal from the .~
2~037~7 standpoint of melting, flowing, and compatibility with biological tissue, is a collagen-like substance which has been modified by dissolving collagen in water and modifying the thusly dissolved collagen to render its 5 surface charge effectively more positive than prior to modification. This material is well known and is disclosed, e.g., in U.S. Patent 4,238,480. The modified collagen is freeze-dried to form a solid mass of gelatin. In accordance with the teachings of the 10 present invention, this mass of gelatin, alone orin combination with other collagen material, may be formed in the shape of a rod, strip, film or flake and utilized as a filler in a laser welding procedure.
Other forms of collagen which are suitable for use in the present invention include Semed F, a collagen preparation manufactured in native fiber form without any chemical or enzymatic modifications, and Semed S, a lyophilized collagen powder extracted from fresh bovine hides. Each of these products is 20 available from Semex Medical, Frazer, Pennsylvania.
The Semed F material is a Type I collagen (greater than 95~), while the Semed S is a mixture of Type I
and Type III collagen macromolecules in which the shape and dimension of tropocollagen in its natural 25 helical orientation is retained.
Either of the Semed S and Semed F collagen material may be formed into welding filler metal by suspending a suitable amount (usually between about 0.5 and lO weight percent) of the material in 30 deionized water to form a viscous solution followed by drying the solution under the action of heat or by freeze-drying of the solution, followed by vacuum treating and heating steps. As above with the gelatin material, the final shape of the material can be in 35 the form of a rod, strip, powder, etc. A paste formulation may also be formed by dissolving - , . : . - ~ :., -:
.
:
,~
.
W092/14513 PCT/US92/011~
g _ i 21~3727 relatively large amounts of the material in relatively small amounts of saline or deionized water.
The shapes of these formed materials are solid and soft but firm. These materials may be readily 5 sliced or cut to the desired sizes for use in the laser welding procedure. Also, the desired size and shape can be achieved by freeze-drying the material in a suitably sized mold which is configured to the desired size and shape of the product. The 10 thicknesses of the rods or sheets can be between 1/4 and 2 mm, depending upon the size of the incision to be joined or area of tissue to be reconstructed. When the paste form is utilized, it may be painted or dropped onto the ares of tissue to be joined or reconstructed. Thus, the surgeon can choose from a wide variety of shapes, sizes, densities, thicknesses and configurations of such filler material depending upon the type of tissue to be welded.
The concentration of the collagen in the liquid 20 which is to be freeze-dried can range from 0.5-10% and preferably 1-5%, with the lower concentrations forming less dense or discontinuous solids. At lower concen-trations of 0.5 to 1%, the Semed F forms a structure which approximates dense cobwebs.
Native collagen film, wherein the film strength is preserved and the triple-helix structure of the collagen polymer is maintained intact, can also be used, either alone or with a plasticizer incorporated therewith. A typical collagen sheet is cast from 30 solution to a thickness of about 1.8 to 2 mm and contains the following composition by weight: collagen 70.3%, plasticizer (typically glycerol or glycerine) 16.9%, water 9%, other 3.8%. Such a material is available from Norwood Medical Products Division of Norwood Industries, Inc., Malverne, Pennsylvania.
When gelatin or other water soluble forms of collagen are utilized, certain advantages are provided . : :
WO92/14513 PCT/US92/011~1 2103727 ~-in that the material will readily polymerize at body temperatures to form a stable subcutaneous gel. In addition, when implanted into the body as filler material in the weld joint, the polymerized material 5 will become rapidly populated by host fibroblasts.
Thus, the material becomes vascularized and can remain histologically, stable for up to 18 months. One problem with gelatin material per se, however, is that it is highly soluble in blood such that the flow of 10 blood across the material will cause it to dissolve.
Thus, gelatin or other soluble collagen material when used alone as laser weld filler should be limited to areas where direct contact with blood is avoided or minimized.
It is more advantageous to use mixtures of the various types of collagen to obtain the most desirable features of each grade. For example, a 50/50 mixture of Semed F and Semed S allows the joint to obtain the higher tensile strength values of the F grade while 20 retaining the superior flow properties of the S grade.
Proportions ranging from 3:1 to 1:3 also form useful mixtures. In addition, the gelatin material described above can be used in combination with the Semed F to achieve similar results.
In addition, low melting polymers or polymeric materials such as copolymers of polyhydroxy buteric acid and valeric acid are useful in certain applications. Plasticizers such as polysaccharides may be included to further lower the melting point of 30 these copolymers to below 200F. These polymers may also be mixed with the collagen or gelatin to increase the strength of the final weld joint. The melting temperature of these polymers should be below about 212 F and on the same order as the melting temper-ature of the collagen (i.e., between about 100-200F).
A wide variety of energy sources may be used to provide the desired energy for effecting the weld .
. ' ~ ' :.
.,. , ~ . . ~
'WO 92~14S13 2 1 ~ 3 72 7 PCl`tUS92/0115~ .
.
V Id ~1 C ~ ~ V ~a w n~ E ~ E E: E v C E
O
~ 01 ~ a z E c c ~ N _ cr O
T
t ¢ ~ ' O O O O O O O O O
~1 t~ X o X X X X X X X X X
m z E 'q N
- o oo o o O O O
X X X X X X X X X X
N N 1~ I ~4 ~ 0 _ --T
Z~D ~D O 11~ N CO --~
3 O .~O O O
V
C , X
Z ~ ~, C
~ o ~E
0~ N _O ~ ~ X X
~
, ' , . ' . . . ' ': .
- ~ ' ' .: . : "
l 2 C ~ ~. E
Or. ~ ~ I : O I ~ 1 ~ 0 . ~ o ~ C
r, ,~, ~ ~
~ U ~ Z ~ -- Z ~Z Z .~ 'u ~ ~U V
U Z
~a ~C ~z ~ .
~ ~ 3~ O` O
w z ~q ' .' ~1 _~ ~ 3 .:
W Cl Ll 0 0 0 ,a ~D Ql o o ~n u ~ u u u t) tl ~ 1~ 1:1 C 1~1 a C ~ ~ C ~ I ~ . ~ .
Ll '~ I O ~ 1 C ~ c ~J
D. V~ Z V~ N !r ~ ~: U 3 ~ 0~ ' u e v 3 ,, a ~. C ' ~ ~ 0 u e N
e a o E I O O J e ~ E 0 v ~
u~ ~ E--~
v .c ~ ` Q'c o c o o o ~ oJ E
. ~ ~~ O U ~ O .~ C
3 N ~ .. ~ X
~ .C ~
~ ~ ~ U U Ul O 3 o ~ a, ~ 0cc O u) u ~ ~J - - - r ~~ ~-~ .c a ~ g ~ E
.
.
WO92/14513 ~ 10 3 7 2 7 PCT/US92/011 . .
repair. Typical laser devices are listed in Tables I
and II. Low wattage laser energy devices, such as those utilizing argon or CO2, would be the most useful for such welding because of their lower energy output.
5 Higher energy output devices, such as electrostatic and RF frequency coagulators (available from Everest, ValleyLab, or Medtronics) using bipolar tips can also be used to denature or melt the collagen filler materials. Since these devices have greater power input, they can burn the collagen to a greater extent than the argon or CO2 lasers. One skilled in the art, however, is able to control and successfully utilize these higher power devices in accordance with the teachings of the present invention.
An argon beam coagulator, such as those made by Beacon Laboratories or Birtcher, are also suitable since they provide an easily controllable flame or heat source which can be utilized to melt the filler material and surrounding tissue to form the weld joint.
The protocol for the process is further appreciated by reference to FIG. l. An incision l0 in a blood vessel 20 is closed by first applying three approximating sutures 30a, 30b and 30 followed by heating the tissue on either side of the incision with the laser 40. Filler material (e.g., collagen) is applied to the incision by placing the tip of welding rod S0 into the laser beam near the heated portion of the incision. The filler material 50 is literally 30 melted (i.e., denatured) to provide additional collagen which flows onto or over the incision, mixes with the melted or denatured tissue, and thereafter cools and fuses to the underlying tissue substrate.
FIG. 2 shows a detail of the joint as it is being made by this procedure.
As noted above, the use of such additional collagen material allows the tensile strength of the - .
. , ~ , .
- , . : . . ~ , ..
.
, .
W092/14513 `~ PCT/US92/011~ ' .. . . . .
joint to be significantly increased over weld joints which do not include additional collagen filler material. This difference in tensile strength is due to the fact that the collagen filler material provides 5 an additional collagen molecular substrate specifically in the area to be joined. The present technique therefore is analogous to the tungsten inert gas ("TIG") welding of metals such as steel or aluminum. In the TIG process, additional filler metal is almost always used on thin sections. Since the biological tissue to be joined is often relatively thin, similar improvements are obtained when using a filler material than by attempting to make the joint without such filler material.
It has been found that a C02 or argon laser with a half to one watt power is eminently suitable for making this type of joint. As noted above electrostatic generators can also be used. In addition, an argon beam electrocoagulator operated at 15-50 volts and 5-20 watts can also be used to denature and melt the collagen welding rod materials and surrounding tissue.
In an attempt to maintain the temperature of the tissue joint at a relatively low value, saline can be 25 used. This is accomplished by dipping the collagen welding rod into saline prior to placing the saline dipped collagen welding rod adjacent to joint area or by dripping saline into the weld. In actual testing, saline cooling makes a different of approximately 23C
in the joint area (e.g., about 47C compared to about 70C without saline cooling).
The present invention resolves many of the problems of the prior art. When welding biological tissues, it is difficult to achieve uniformly good 3 results. This problem is due in part to the inability of the surgeon to uniformly melt the biological tissue on each side of the joint to obtain a satisfactory . . . ,- . -, : .
'"' ' -' ~ ~ ' : " .:: ,:
: .
::
WO92~1451~ 210 3 7 2 ~ PCT/US92/011~
~` - 15 -weld. With the use of collagen welding rod as proposed by the present invention, additional collagen material is supplied to the joint from the rod to compensate for any overmelting of tissue on either 5 side of the joint. This also provides an abundance of additional material to seal voids or other defects caused by overheating of tissue. Thus, the reproducibility of the procedure and the attainment of uniform weld joints are significantly improved by the 10 present invention.
All different types of biological tissue may be treated according to the present procedures. For example, all types of blood vessels, including veins, arteries, etc. in the vascular system can be connected or repaired, as can muscle, fascia, tendon, skin or even nerve material.
Another procedure in accordance with the present invention is illustrated in FIG 3. In that FIG., the incision is covered with a flat strip of collagen 20 material 60 along its entire length. The adjacent blood vessel walls 70 on each side of the incision are overlapped by this strip 60 of collagen material. The laser 80 heats the strip of material and the adjacent blood vessel walls 70 to denature those materials into a mass which then solidifies to form the laser welded joint. Again, the use of the strip of collagen material 60 facilitates the welding operation and improves the resultant tensile strength of the weld joint. FIG. 4 shows a detail of the use of the strip 30 material to fill a tissue defect or other lesion.
In an alternate embodiment of the invention, in order to insure that the placement of the welding rod remains in the appropriate position for allowing denatured collagen to flow into the jolnt area, it is possible to secure or attach the filler metal to the area to be joined. An easy way to accomplish this is to dip the filler material into fibrin glue prior to .
: . .
- , - : ~ , ' ' ' . : ~ : ~ :
. - - , .
. : . . .. . . . . ~ , WO92/14513 ;j PCT/US92/011~>
2103727 - 16 ~
applying the ~iller material to the area to be welded.
In addition to retaining the filler in the appropriate area desired, the fibrin glue or other biological tissue adhesive also appears to act as a flux which assists in directing the denatured or melted collagen material into the incision.
The welding procedure is made easier by utilizing an energy absorbing aid in conjunction with the filler material. These aids assist in the absorption of energy by the filler material so that the denaturing or melting process is more efficient, i.e., more of the energy is directly utilized to denature or melt the filler material rather than is scattered to other areas of the body near the tissue to be repaired.
Preferred energy absorbing aids include any of the numerous dyes, such as Vital Green or Basic Red.
The color of the absorbing acid or dye should match the wavelength of the transmitted energy for optimum results. However, any substance, preferably which is in liquid form and which is capable of absorbing energy and transmitting the absorbed energy to the filler material, may be used. Often, the blood or hemoglobin of the patient may be used. Water or other physiologic solutions are also useful.
Advantageously, the energy absorbing aid is applied to the filler material to form a coating thereon. The filler material may simply be dipped into a reservoir of the energy absorbing aid. More complex arrangements, such as a spraying device or pump, can be used to apply the energy absorbing aid to the filler material, if desired.
In addition, the energy absorbing aid can be applied to the tissue to be repaired. This is easily ;
accomplished, since the tissue is often cut and is bleeding to provide a suitable source of energy absorbing aid, i.e., blood. Also, the use of a dye is advantageous since it allows the joint to be easily : . -- . .
, ~ :
::
WO92/14513 210 3 7 2 7 PCT/US92/011~
viewed by the surgeon to determine exactly where the welding procedure must be conducted.
In yet another embodiment, the welding procedure can be performed endoscopically: i.e., access to the area desired to be repaired or reconstructed can be made through multiple naturally or surgically created apertures: one aperture is used for insertion of the laser, another for the insertion of the filler material, and a third for monitoring the procedure with an optical fiber connected to an eye-piece or a video camera while the procedure can be visually observed through the eyepiece or camera, the presentation of the procedure on a monitor is preferred because the incision can be viewed in an enlarged mode so that the surgeon can accurately determine the proper placement of the filler material and completion of the joint.
Examples The following examples illustrate applications of the welding procedures of the present invention. A
dog was anesthetized and its neck and groin area prepared for access. The carotid artery and jugular vein were exposed and clamped, and a one inch incision was made in each one. An argon laser operated at about one-half watt was used to reweld the clamped joints with one of Semed S, Semed F, and modified collagen material (i.e., gelatin) as described above.
Sutures were included at each end of the incision to prevent propagation of the incision during welding.
The gelatin samples welded beautifully in that they readily melted, and simply and easily filled incision and rapidly formed a solld weld joint.
However, upon exposure to blood, this material was solubilized by the blood which broke through the weld due to dissolution. The Semed F samples did not flow as readily into the joint, but once the joint was .
- , , , . .................. , . . :
, : . , - . . .
,:
WO92/14513 PCT/US92/011~, made, a very high tensile strength repair was obtained. The performance of the Semed S was intermediate between the modified polymer and Semed F
both with respect to joint strength and fluidity.
5 Mixtures of either Semed S or modified collagen (gelatin) with the Semed F material, in a 50/50 ratio provides the benefits of each material are achieved in a single filler rod material.
To aid in the absorption of energy by the filler 10 material and the tissue to be repaired, Vital Green dye was applied to the tissue and filler material.
The filler material was merely dipped into the dye.
The dye coated filler and tissue greatly facilitated the welding operation as it was easier to apply the optical energy to the desired locations.
FIGS. 5-ll illustrate the usefulness of the welding procedures of the present invention by showing its effects on various welded tissue joints. These were generated by operating on dogs to incise normal 20 tissue, followed by welding to repair the incision.
FIG. 5 shows the results of a dog aorta which was welded with the mixed collagen filler material two days after welding. The nuclei and cell structure of the aorta appear normal and no karyolysis is evident.
FIG. 6 shows this filler material and the welded vena cava adjacent the aorta of FIG. 5 two weeks after welding. The welded vena cava and collagen filler material are juxtaposed to form an intact weld joint across the incision. No evidence of thrombosis is seen at this joint or surrounding tissue.
FIGS. 7 and 8 further illustrate the weld joint of FIG. 6. These FIGS. show the filler material bridging the incision. In FIG. 7, the collagen filler material appears as a large mass at the upper left 35 hand corner of the photograph. The incision in the vena cava is just visible at the point where the material was transsected prior to placing in fixative.
.
.
- ~ :: . . . .
. ~ . . ..
~WO92/14513 2 1 0 3 7 2 7 PCT/US92/011~
s ., ., -- 1 9 . ,~
The fibrillar structure of the welding material is evident. In FIG. 8, a low concentration of welding material as a thin band bridges the incision which appears at the lower left corner of the 5 photomicrograph. The incision is closed by this material, and the vena cava architecture is intact.
FIG. 9 illustrates welded skin tissue. The ' .
gelatin welding material bridges the incision but has relatively poor tensile strength when tested about ten 10 minutes after making the weld joint. The weld joint was properly made and, as noted above, the strength of the welded joint can be improved by including collagen in the filler material.
FIG. lO illustrates a welded coating of gelatin 15 material placed under the skin. The coating is able to hold the skin together for up to about ten minutes before losing strength due to saturation and dissolution in blood. Again, proper selection of a welding material which includes insoluble collagen 20 will provide a higher strength coating.
FIG. ll illustrates the welding of muscle tissue with a mixed collagen filler material. The incision is clearly filled and joined by the welding material to produce a strong joint.
In the preceding FIGS., an Eximer CO2 laser was utilized as the energy source, with basic red dye or blood used as the energy absorbing aid. No difference in performance was seen using either fluid.
A wide variety of devices can be used to place 30 the welding material in the vicinity of the tissue to be repaired. For example, in addition to the above-described arrangements, a tube of collagen welding material can be placed concentrically around the laser. Thus, the surgeon can urge the tube forward toward the distal end of the laser, where it can be melted by the energy. The tube can be dyed with an energy absorbing aid to assist in the melting .: . . : . -. -.
WO92/14513 PCT/US92/011~
procedure. As the end of the tube melts, the surgeon can urge further material into the path of the laser beam. To retain the area to be repaired in the proper position, a pair of grasping forceps can also be used.
In addition, for the repair of a blood vessel, a catheter or stent which includes a tubular covering of filler material can be introduced into the vessel beneath the area to be repaired. Thereafter, the laser welding procedure is conducted on the outside of 10 the vessel, to melt both the vessel and the collagenmaterial which is immediately below. Again, if desired, the collagen material can be dyed to increase its absorption of energy and melting efficiency.
Both bi-polar and uni-polar RF electrodes were 1~ also utilized to denature or melt various samples of modified gelatin, Semed F and Semed S, both alone and in combination, into arteriotomies and venotomies. A
vascular anastomosis was also crated using Semed F in accordance with the above-described welding technique.
20 The weld joint was observed to be of high tensile strength. Also, attempts at approximating muscle, tendon and skin have been successfully completed.
It is believed that numerous variations and modifications may be devised by those skilled in the 25 art to the specifically disclosed invention, and it is intended that the appended claims cover all such modifications and embodiments as would fall within the true spirit and scope of the present invention.
~ . . . , , . ~ ~ .
.
produce thermal heating of the biological tissue to degree suitable for denaturing the tissue proteins such that the collagenous elements of the tissue form a "biological glue" which seals the tissue to effect 5 the joining. This glue is later reabsorbed by the body during the healing process. The patent discloses a number of different types of lasers with preference stated for the Nd:YAG type, because its particular wavelength allows optical energy to propagate without 10 substantial attenuation through water and/or blood for absorption in the tissue to be repaired.
Despite these improvements, however, the weakness of the weld joint still remains as the primary disadvantage of this procedure and extensive current research is being conducted in an attempt to improve on that deficiency. I have now invented a simple yet elegant welding procedure for biological tissue utilizing laser or RF energy which overcomes the shortcomings of the prior art.
SUMMARY OF THE INVENTION
The present invention relates to a method of joining or reconstructing biological tissue which comprises applying energy to the biological tissue 25 while providing a suitable filler material thereto;
denaturing or melting the filler material and adjacent biological tissue with the energy to cause mixing of the denatured or melted filler material and biological tissue, thus joining or reconstructing such tissue.
The filler material is preferably collagen and one embodiment of the inventive method includes adhesively attaching the collagen filler material to the biological tissue to assure proper placement thereupon. This may be achieved by applying the 35 collagen material adjacent the biological material with fibrin glue or other biological tissue adhesive.
, , , ,, . ..; ~
- .
' WO92/14513 ~ - PCT/US92/011~.
2103727 - 4 - f~
~_,f This method may also include applying an energy absorption aid to one of the filler materials or the biological tissue, or both, to facilitate absorption of the applied energy thereby. Generally, the energy 5 absorbing aid is applied to preselected locations prior to the application of energy thereto, and it also assists in visually determining the areas to be joined or reconstructed. Preferred energy absorbing aids include dyes, such as Vital Green or Basic Red, 10 blood or water.
Often, the biological tissue includes an incision and the method enables the surgeon to enclose the incision by the mixing and joining of the denatured or melted filler material and biological tissue. If 15 desired, spaced sutures may be placed in tissue surrounding the incision to fix the position of adjacent tissue.
The filler material may be prepared by dissolving a predetermined amount of collagen material in water 20 to form a solution, followed by drying or freeze drying of the solution in the desired form and shape of the collagen filler material. Preferably, the collagen material used to prepare the filler material is a mixture of an insoluble collagen material and a soluble collagen material in a weight ratio of about 1:3 to 3:1.
The present method also contemplates applying a physiologically acceptable solution to one of the collagen filler materials or the biological tissue to control the temperature of the joint due to the energy imparted thereto. The applied energy may be provided as optical energy (i.e., by a laser), from an RF
generator, or by an inert gas beam coagulator, since these devices have sufficient power dissipation to cause the energy or heat that they produce to be absorbed by the tissue and collagen filler material.
The heat provided by the coagulator or which is :, ~
:, ., `
..
.
WO92/14513 210 3 7 2 7 PCT/US92/011~
......
converted from the applied laser or RF energy) generally should be within a range bounded by the minimum absorption rate at which the protein elements of the tissue and collagen filler material are 5 converted to melted collagen and by a maximum absorption rate which would cause water in the tissue or collagen filler material to boil. The RF energy may be provided by uni- or bipolar techniques, since each will melt the collagen filler material into the 10 defect or joint area. Thus, the protein elements of the tissue and the collagen filler metal can be melted or denatured, mixed or combined, and then cooled to form a weld joint.
When the biological tissue includes a lesion, the method further comprises forming a seal of collagen material near or upon the lesion. When the lesion comprises at least two separated segments of biological tissue, the method further comprises placing the two segments of tissue in close proximity, 20 and guiding the energy source and collagen filler material into the area of their junction for joining or reconstruction thereof.
The features and advantages of the present invention are more readily understood when read in conjunction with the attached drawing figures wherein FIG. l is a perspective view of the use of a collagen 30 welding rod for closing an incision in a blood vessel with the use of a laser or bipolar RF electrode;
FIG. 2 is a detail of the denatured or melted collagen material in the weld joint of FIG. l;
FIG. 3 is a perspective view of the use of a 35 collagen strip in the laser joining of an incision;
and WO92/145]3 PCT/US92/011~
~lU~7~7: ~ I
FIG. 4 is a detail of denaturecl or melted collagen material being applied upon a tissue defect or lesion; and FIGS. 5-11 are photomicrographs which show the 5 morphology of various welded tissue joints.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
It is well known that biological tissue includes cell layers in a protein framework which provides 10 tensile strength. The proteins are amino acids, and it is known that the application of heat or optical energy can denature such proteins. When the source of heat or energy is removed, the proteins if not totally broken down cool and begin to reconfigure and form an 15 approximate replication of the prior tissue structure.
The prior art teaches that the application of either optical energy from a laser or RF energy from a suitable generator could be used to bring the temperature of the biological tissue above room 20 temperature but below the boiling point of water (preferably between 45-75F and more prefer 60-70~F).
The denaturing of collagen, a major source of protein in the human body, can also be achieved by the application of energy, and is believed to go into 25 solution and form a type of "biological glue" which seals the incision or discontinuity in the biological tissue. Thus, it is possible to seal lesions, anastomose a severed or incised vessel or to -~
reconstruct diseased or damaged tissue.
I have found that a major disadvantage of such laser welding procedures for rejoining incised tissue is that insufficient tissue material is present for completing a successful joint. When optical energy from the laser actually denatures or melts the tissue in the areas to be joined, a portion of the tissue thickness is reduced so that the denatured materials can flow towards each other and stic~; together to form . .
.
-, , - .. . .
. - - . , ~ . . , - , : , ..
, ~; - 7 -the joint. On relatively thin sections of tissue to be joined, such as in repairing an incised blood vessel wall, there is insufficient denatured material in the joint area for providing a sound, high tensile 5 strength connection.
Collagen is known for use in the medical field as a material for repairing tissue damage caused by thermal, chemical or mechanical trauma (see, e.g., "Collagen: Its Place In the Medical Industry" by J.M.
10 Pachence, et al., Medical Device and Diagnostic Industry, January, 1987). I have found that this material can be used as a filler which can be placed in the path of the laser beam, melted or denatured, and directed into the incision or the tissue which is to be reconstructed. Bipolar or unipolar RF energy will also yield the same or substantially similar results. Based on qualitative observations, the additional collagen molecules provided by the filler material allows the tensile strength of the welded 20 incision to be significantly increased.
The application of optical energy and the use of additional collagen material provides several advantages in addition to increased tensile strength.
The healing time of the wound is accelerated because 25 blood supply to the affected tissue can be reestablished immediately after the surgical procedure. In addition, little or no scarring is produced because sutures are eliminated or substantially minimized. Furthermore, the various 30 techniques disclosed herein enhance the accuracy of the welding procedure thus avoiding optical or RF
energy damage to adjacent or unintended areas of such tissl~e.
A wide variety of materials may be used as a 35 filler in this welding procedure. The most common source is collagen which may be obtained from bovine hides. Another material, which is ideal from the .~
2~037~7 standpoint of melting, flowing, and compatibility with biological tissue, is a collagen-like substance which has been modified by dissolving collagen in water and modifying the thusly dissolved collagen to render its 5 surface charge effectively more positive than prior to modification. This material is well known and is disclosed, e.g., in U.S. Patent 4,238,480. The modified collagen is freeze-dried to form a solid mass of gelatin. In accordance with the teachings of the 10 present invention, this mass of gelatin, alone orin combination with other collagen material, may be formed in the shape of a rod, strip, film or flake and utilized as a filler in a laser welding procedure.
Other forms of collagen which are suitable for use in the present invention include Semed F, a collagen preparation manufactured in native fiber form without any chemical or enzymatic modifications, and Semed S, a lyophilized collagen powder extracted from fresh bovine hides. Each of these products is 20 available from Semex Medical, Frazer, Pennsylvania.
The Semed F material is a Type I collagen (greater than 95~), while the Semed S is a mixture of Type I
and Type III collagen macromolecules in which the shape and dimension of tropocollagen in its natural 25 helical orientation is retained.
Either of the Semed S and Semed F collagen material may be formed into welding filler metal by suspending a suitable amount (usually between about 0.5 and lO weight percent) of the material in 30 deionized water to form a viscous solution followed by drying the solution under the action of heat or by freeze-drying of the solution, followed by vacuum treating and heating steps. As above with the gelatin material, the final shape of the material can be in 35 the form of a rod, strip, powder, etc. A paste formulation may also be formed by dissolving - , . : . - ~ :., -:
.
:
,~
.
W092/14513 PCT/US92/011~
g _ i 21~3727 relatively large amounts of the material in relatively small amounts of saline or deionized water.
The shapes of these formed materials are solid and soft but firm. These materials may be readily 5 sliced or cut to the desired sizes for use in the laser welding procedure. Also, the desired size and shape can be achieved by freeze-drying the material in a suitably sized mold which is configured to the desired size and shape of the product. The 10 thicknesses of the rods or sheets can be between 1/4 and 2 mm, depending upon the size of the incision to be joined or area of tissue to be reconstructed. When the paste form is utilized, it may be painted or dropped onto the ares of tissue to be joined or reconstructed. Thus, the surgeon can choose from a wide variety of shapes, sizes, densities, thicknesses and configurations of such filler material depending upon the type of tissue to be welded.
The concentration of the collagen in the liquid 20 which is to be freeze-dried can range from 0.5-10% and preferably 1-5%, with the lower concentrations forming less dense or discontinuous solids. At lower concen-trations of 0.5 to 1%, the Semed F forms a structure which approximates dense cobwebs.
Native collagen film, wherein the film strength is preserved and the triple-helix structure of the collagen polymer is maintained intact, can also be used, either alone or with a plasticizer incorporated therewith. A typical collagen sheet is cast from 30 solution to a thickness of about 1.8 to 2 mm and contains the following composition by weight: collagen 70.3%, plasticizer (typically glycerol or glycerine) 16.9%, water 9%, other 3.8%. Such a material is available from Norwood Medical Products Division of Norwood Industries, Inc., Malverne, Pennsylvania.
When gelatin or other water soluble forms of collagen are utilized, certain advantages are provided . : :
WO92/14513 PCT/US92/011~1 2103727 ~-in that the material will readily polymerize at body temperatures to form a stable subcutaneous gel. In addition, when implanted into the body as filler material in the weld joint, the polymerized material 5 will become rapidly populated by host fibroblasts.
Thus, the material becomes vascularized and can remain histologically, stable for up to 18 months. One problem with gelatin material per se, however, is that it is highly soluble in blood such that the flow of 10 blood across the material will cause it to dissolve.
Thus, gelatin or other soluble collagen material when used alone as laser weld filler should be limited to areas where direct contact with blood is avoided or minimized.
It is more advantageous to use mixtures of the various types of collagen to obtain the most desirable features of each grade. For example, a 50/50 mixture of Semed F and Semed S allows the joint to obtain the higher tensile strength values of the F grade while 20 retaining the superior flow properties of the S grade.
Proportions ranging from 3:1 to 1:3 also form useful mixtures. In addition, the gelatin material described above can be used in combination with the Semed F to achieve similar results.
In addition, low melting polymers or polymeric materials such as copolymers of polyhydroxy buteric acid and valeric acid are useful in certain applications. Plasticizers such as polysaccharides may be included to further lower the melting point of 30 these copolymers to below 200F. These polymers may also be mixed with the collagen or gelatin to increase the strength of the final weld joint. The melting temperature of these polymers should be below about 212 F and on the same order as the melting temper-ature of the collagen (i.e., between about 100-200F).
A wide variety of energy sources may be used to provide the desired energy for effecting the weld .
. ' ~ ' :.
.,. , ~ . . ~
'WO 92~14S13 2 1 ~ 3 72 7 PCl`tUS92/0115~ .
.
V Id ~1 C ~ ~ V ~a w n~ E ~ E E: E v C E
O
~ 01 ~ a z E c c ~ N _ cr O
T
t ¢ ~ ' O O O O O O O O O
~1 t~ X o X X X X X X X X X
m z E 'q N
- o oo o o O O O
X X X X X X X X X X
N N 1~ I ~4 ~ 0 _ --T
Z~D ~D O 11~ N CO --~
3 O .~O O O
V
C , X
Z ~ ~, C
~ o ~E
0~ N _O ~ ~ X X
~
, ' , . ' . . . ' ': .
- ~ ' ' .: . : "
l 2 C ~ ~. E
Or. ~ ~ I : O I ~ 1 ~ 0 . ~ o ~ C
r, ,~, ~ ~
~ U ~ Z ~ -- Z ~Z Z .~ 'u ~ ~U V
U Z
~a ~C ~z ~ .
~ ~ 3~ O` O
w z ~q ' .' ~1 _~ ~ 3 .:
W Cl Ll 0 0 0 ,a ~D Ql o o ~n u ~ u u u t) tl ~ 1~ 1:1 C 1~1 a C ~ ~ C ~ I ~ . ~ .
Ll '~ I O ~ 1 C ~ c ~J
D. V~ Z V~ N !r ~ ~: U 3 ~ 0~ ' u e v 3 ,, a ~. C ' ~ ~ 0 u e N
e a o E I O O J e ~ E 0 v ~
u~ ~ E--~
v .c ~ ` Q'c o c o o o ~ oJ E
. ~ ~~ O U ~ O .~ C
3 N ~ .. ~ X
~ .C ~
~ ~ ~ U U Ul O 3 o ~ a, ~ 0cc O u) u ~ ~J - - - r ~~ ~-~ .c a ~ g ~ E
.
.
WO92/14513 ~ 10 3 7 2 7 PCT/US92/011 . .
repair. Typical laser devices are listed in Tables I
and II. Low wattage laser energy devices, such as those utilizing argon or CO2, would be the most useful for such welding because of their lower energy output.
5 Higher energy output devices, such as electrostatic and RF frequency coagulators (available from Everest, ValleyLab, or Medtronics) using bipolar tips can also be used to denature or melt the collagen filler materials. Since these devices have greater power input, they can burn the collagen to a greater extent than the argon or CO2 lasers. One skilled in the art, however, is able to control and successfully utilize these higher power devices in accordance with the teachings of the present invention.
An argon beam coagulator, such as those made by Beacon Laboratories or Birtcher, are also suitable since they provide an easily controllable flame or heat source which can be utilized to melt the filler material and surrounding tissue to form the weld joint.
The protocol for the process is further appreciated by reference to FIG. l. An incision l0 in a blood vessel 20 is closed by first applying three approximating sutures 30a, 30b and 30 followed by heating the tissue on either side of the incision with the laser 40. Filler material (e.g., collagen) is applied to the incision by placing the tip of welding rod S0 into the laser beam near the heated portion of the incision. The filler material 50 is literally 30 melted (i.e., denatured) to provide additional collagen which flows onto or over the incision, mixes with the melted or denatured tissue, and thereafter cools and fuses to the underlying tissue substrate.
FIG. 2 shows a detail of the joint as it is being made by this procedure.
As noted above, the use of such additional collagen material allows the tensile strength of the - .
. , ~ , .
- , . : . . ~ , ..
.
, .
W092/14513 `~ PCT/US92/011~ ' .. . . . .
joint to be significantly increased over weld joints which do not include additional collagen filler material. This difference in tensile strength is due to the fact that the collagen filler material provides 5 an additional collagen molecular substrate specifically in the area to be joined. The present technique therefore is analogous to the tungsten inert gas ("TIG") welding of metals such as steel or aluminum. In the TIG process, additional filler metal is almost always used on thin sections. Since the biological tissue to be joined is often relatively thin, similar improvements are obtained when using a filler material than by attempting to make the joint without such filler material.
It has been found that a C02 or argon laser with a half to one watt power is eminently suitable for making this type of joint. As noted above electrostatic generators can also be used. In addition, an argon beam electrocoagulator operated at 15-50 volts and 5-20 watts can also be used to denature and melt the collagen welding rod materials and surrounding tissue.
In an attempt to maintain the temperature of the tissue joint at a relatively low value, saline can be 25 used. This is accomplished by dipping the collagen welding rod into saline prior to placing the saline dipped collagen welding rod adjacent to joint area or by dripping saline into the weld. In actual testing, saline cooling makes a different of approximately 23C
in the joint area (e.g., about 47C compared to about 70C without saline cooling).
The present invention resolves many of the problems of the prior art. When welding biological tissues, it is difficult to achieve uniformly good 3 results. This problem is due in part to the inability of the surgeon to uniformly melt the biological tissue on each side of the joint to obtain a satisfactory . . . ,- . -, : .
'"' ' -' ~ ~ ' : " .:: ,:
: .
::
WO92~1451~ 210 3 7 2 ~ PCT/US92/011~
~` - 15 -weld. With the use of collagen welding rod as proposed by the present invention, additional collagen material is supplied to the joint from the rod to compensate for any overmelting of tissue on either 5 side of the joint. This also provides an abundance of additional material to seal voids or other defects caused by overheating of tissue. Thus, the reproducibility of the procedure and the attainment of uniform weld joints are significantly improved by the 10 present invention.
All different types of biological tissue may be treated according to the present procedures. For example, all types of blood vessels, including veins, arteries, etc. in the vascular system can be connected or repaired, as can muscle, fascia, tendon, skin or even nerve material.
Another procedure in accordance with the present invention is illustrated in FIG 3. In that FIG., the incision is covered with a flat strip of collagen 20 material 60 along its entire length. The adjacent blood vessel walls 70 on each side of the incision are overlapped by this strip 60 of collagen material. The laser 80 heats the strip of material and the adjacent blood vessel walls 70 to denature those materials into a mass which then solidifies to form the laser welded joint. Again, the use of the strip of collagen material 60 facilitates the welding operation and improves the resultant tensile strength of the weld joint. FIG. 4 shows a detail of the use of the strip 30 material to fill a tissue defect or other lesion.
In an alternate embodiment of the invention, in order to insure that the placement of the welding rod remains in the appropriate position for allowing denatured collagen to flow into the jolnt area, it is possible to secure or attach the filler metal to the area to be joined. An easy way to accomplish this is to dip the filler material into fibrin glue prior to .
: . .
- , - : ~ , ' ' ' . : ~ : ~ :
. - - , .
. : . . .. . . . . ~ , WO92/14513 ;j PCT/US92/011~>
2103727 - 16 ~
applying the ~iller material to the area to be welded.
In addition to retaining the filler in the appropriate area desired, the fibrin glue or other biological tissue adhesive also appears to act as a flux which assists in directing the denatured or melted collagen material into the incision.
The welding procedure is made easier by utilizing an energy absorbing aid in conjunction with the filler material. These aids assist in the absorption of energy by the filler material so that the denaturing or melting process is more efficient, i.e., more of the energy is directly utilized to denature or melt the filler material rather than is scattered to other areas of the body near the tissue to be repaired.
Preferred energy absorbing aids include any of the numerous dyes, such as Vital Green or Basic Red.
The color of the absorbing acid or dye should match the wavelength of the transmitted energy for optimum results. However, any substance, preferably which is in liquid form and which is capable of absorbing energy and transmitting the absorbed energy to the filler material, may be used. Often, the blood or hemoglobin of the patient may be used. Water or other physiologic solutions are also useful.
Advantageously, the energy absorbing aid is applied to the filler material to form a coating thereon. The filler material may simply be dipped into a reservoir of the energy absorbing aid. More complex arrangements, such as a spraying device or pump, can be used to apply the energy absorbing aid to the filler material, if desired.
In addition, the energy absorbing aid can be applied to the tissue to be repaired. This is easily ;
accomplished, since the tissue is often cut and is bleeding to provide a suitable source of energy absorbing aid, i.e., blood. Also, the use of a dye is advantageous since it allows the joint to be easily : . -- . .
, ~ :
::
WO92/14513 210 3 7 2 7 PCT/US92/011~
viewed by the surgeon to determine exactly where the welding procedure must be conducted.
In yet another embodiment, the welding procedure can be performed endoscopically: i.e., access to the area desired to be repaired or reconstructed can be made through multiple naturally or surgically created apertures: one aperture is used for insertion of the laser, another for the insertion of the filler material, and a third for monitoring the procedure with an optical fiber connected to an eye-piece or a video camera while the procedure can be visually observed through the eyepiece or camera, the presentation of the procedure on a monitor is preferred because the incision can be viewed in an enlarged mode so that the surgeon can accurately determine the proper placement of the filler material and completion of the joint.
Examples The following examples illustrate applications of the welding procedures of the present invention. A
dog was anesthetized and its neck and groin area prepared for access. The carotid artery and jugular vein were exposed and clamped, and a one inch incision was made in each one. An argon laser operated at about one-half watt was used to reweld the clamped joints with one of Semed S, Semed F, and modified collagen material (i.e., gelatin) as described above.
Sutures were included at each end of the incision to prevent propagation of the incision during welding.
The gelatin samples welded beautifully in that they readily melted, and simply and easily filled incision and rapidly formed a solld weld joint.
However, upon exposure to blood, this material was solubilized by the blood which broke through the weld due to dissolution. The Semed F samples did not flow as readily into the joint, but once the joint was .
- , , , . .................. , . . :
, : . , - . . .
,:
WO92/14513 PCT/US92/011~, made, a very high tensile strength repair was obtained. The performance of the Semed S was intermediate between the modified polymer and Semed F
both with respect to joint strength and fluidity.
5 Mixtures of either Semed S or modified collagen (gelatin) with the Semed F material, in a 50/50 ratio provides the benefits of each material are achieved in a single filler rod material.
To aid in the absorption of energy by the filler 10 material and the tissue to be repaired, Vital Green dye was applied to the tissue and filler material.
The filler material was merely dipped into the dye.
The dye coated filler and tissue greatly facilitated the welding operation as it was easier to apply the optical energy to the desired locations.
FIGS. 5-ll illustrate the usefulness of the welding procedures of the present invention by showing its effects on various welded tissue joints. These were generated by operating on dogs to incise normal 20 tissue, followed by welding to repair the incision.
FIG. 5 shows the results of a dog aorta which was welded with the mixed collagen filler material two days after welding. The nuclei and cell structure of the aorta appear normal and no karyolysis is evident.
FIG. 6 shows this filler material and the welded vena cava adjacent the aorta of FIG. 5 two weeks after welding. The welded vena cava and collagen filler material are juxtaposed to form an intact weld joint across the incision. No evidence of thrombosis is seen at this joint or surrounding tissue.
FIGS. 7 and 8 further illustrate the weld joint of FIG. 6. These FIGS. show the filler material bridging the incision. In FIG. 7, the collagen filler material appears as a large mass at the upper left 35 hand corner of the photograph. The incision in the vena cava is just visible at the point where the material was transsected prior to placing in fixative.
.
.
- ~ :: . . . .
. ~ . . ..
~WO92/14513 2 1 0 3 7 2 7 PCT/US92/011~
s ., ., -- 1 9 . ,~
The fibrillar structure of the welding material is evident. In FIG. 8, a low concentration of welding material as a thin band bridges the incision which appears at the lower left corner of the 5 photomicrograph. The incision is closed by this material, and the vena cava architecture is intact.
FIG. 9 illustrates welded skin tissue. The ' .
gelatin welding material bridges the incision but has relatively poor tensile strength when tested about ten 10 minutes after making the weld joint. The weld joint was properly made and, as noted above, the strength of the welded joint can be improved by including collagen in the filler material.
FIG. lO illustrates a welded coating of gelatin 15 material placed under the skin. The coating is able to hold the skin together for up to about ten minutes before losing strength due to saturation and dissolution in blood. Again, proper selection of a welding material which includes insoluble collagen 20 will provide a higher strength coating.
FIG. ll illustrates the welding of muscle tissue with a mixed collagen filler material. The incision is clearly filled and joined by the welding material to produce a strong joint.
In the preceding FIGS., an Eximer CO2 laser was utilized as the energy source, with basic red dye or blood used as the energy absorbing aid. No difference in performance was seen using either fluid.
A wide variety of devices can be used to place 30 the welding material in the vicinity of the tissue to be repaired. For example, in addition to the above-described arrangements, a tube of collagen welding material can be placed concentrically around the laser. Thus, the surgeon can urge the tube forward toward the distal end of the laser, where it can be melted by the energy. The tube can be dyed with an energy absorbing aid to assist in the melting .: . . : . -. -.
WO92/14513 PCT/US92/011~
procedure. As the end of the tube melts, the surgeon can urge further material into the path of the laser beam. To retain the area to be repaired in the proper position, a pair of grasping forceps can also be used.
In addition, for the repair of a blood vessel, a catheter or stent which includes a tubular covering of filler material can be introduced into the vessel beneath the area to be repaired. Thereafter, the laser welding procedure is conducted on the outside of 10 the vessel, to melt both the vessel and the collagenmaterial which is immediately below. Again, if desired, the collagen material can be dyed to increase its absorption of energy and melting efficiency.
Both bi-polar and uni-polar RF electrodes were 1~ also utilized to denature or melt various samples of modified gelatin, Semed F and Semed S, both alone and in combination, into arteriotomies and venotomies. A
vascular anastomosis was also crated using Semed F in accordance with the above-described welding technique.
20 The weld joint was observed to be of high tensile strength. Also, attempts at approximating muscle, tendon and skin have been successfully completed.
It is believed that numerous variations and modifications may be devised by those skilled in the 25 art to the specifically disclosed invention, and it is intended that the appended claims cover all such modifications and embodiments as would fall within the true spirit and scope of the present invention.
~ . . . , , . ~ ~ .
.
Claims (35)
1. A method of joining or reconstructing biological tissue which comprises preparing a filler material in a solid shape or form, applying energy to the biological tissue while providing the filler material thereto; and denaturing or melting the filler material and adjacent biological tissue with the applied energy to cause mixing of the denatured or melted filler material and biological tissue, thus joining or reconstructing such tissue.
2. The method of claim 1 which further comprises applying an energy absorption aid to the filler material to facilitate absorption of the energy thereby.
3. The method of claim 2 wherein the energy absorption aid is also applied to the biological tissue to assist in visually determining the areas to be joined or reconstructed.
4. The method of claim 3 wherein the energy absorption aid is applied to preselected locations of the filler material or tissue prior to application of the energy.
5. The method of claim 2 which further comprises selecting the energy absorption agent from Vital Green dye, Basic Red dye, blood, water or a mixture thereof.
6. The method of claim 1 which further comprises placing the filler material upon the biological tissue to assure proper placement thereof prior to applying energy thereto.
7. The method of claim 1 wherein the biological tissue includes an incision and which further comprises enclosing said incision by the mixing and joining of the denatured or melted collagen filler material and biological tissue.
8. The method of claim 7 which further comprises placing spaced sutures in tissue surrounding said incision to fix the position of adjacent tissue.
9. The method of claim 1 which further comprises preparing said filler material by dissolving a predetermined amount of collagen material in water to form a solution, followed by drying of the solution in the desired form and shape of the filler material.
10. The method of claim 1 wherein the filler material is a mixture of an insoluble collagen and a soluble collagen.
11. The method of claim 10 wherein the weight ratio of the soluble collagen to the insoluble collagen is between about 1:3 to 3:1.
12. The method of claim 1 wherein the filler material includes collagen and the applied energy is provided by a laser or RF generator having a power dissipation sufficient to cause the energy to be absorbed by the tissue and the collagen filler material and converted to heat and to be within a range bounded by a minimum absorption rate at which the tissue and collagen filler material are converted to a denatured or melted collagen and by a maximum absorption rate at which water in the tissue or collagen filler material would boil, such that proteins of the tissue and the collagen filler metal can be denatured or melted, mixed or combined and cooled to form a weld joint.
13. The method of claim 1 wherein the biological tissue includes a lesion and wherein the method further comprises forming a seal of filler material near or upon said lesion.
14. The method of claim 13 wherein the lesion comprises at least two separated segments of biological tissue and the method further comprises placing said two segments of tissue in close proximity, and directing said optical energy and filler material into the area of their junction.
15. The method of claim 1 which further comprises adhesively attaching the filler material to the biological tissue to assure proper placement thereof.
16. The method of claim 15 wherein the filler material is attached to the tissue with the use of fibrin glue.
17. The method of claim 1 which further comprises applying a physiologically acceptable solution to one of the filler material or the biological tissue to control the temperature of the joint due to the energy imparted thereto.
18. The method of claim 1 which further comprises applying energy with an argon beam coagulator to melt the tissue and filler material.
19. The method of claim 18 which further comprises operating the argon beam coagulator at between 15-50 volts and 5-20 watts to melt the tissue and filler material.
20. The method of claim 2 which further comprises selecting the filler material to be a low melting polymer or polymeric material.
21. The method of claim 20 which further comprises incorporating a plasticizer into the filler material prior to use in the joining operation.
22. The method of claim 20 which further comprises combining the polymer or polymeric material with collagen or gelatin prior to use in the joining operation.
23. A filler material for use in tissue welding which comprises a solid material of a desired size and shape and in an amount which can be denatured or melted for fusion to tissue to form a high tensile strength tissue weld.
24. The filler material of claim 23 wherein the solid component comprises collagen.
25. The filler material of claim 24 wherein the solid component comprises a mixture of insoluble collagen and soluble collagen.
26. The filler material of claim 25 wherein the weight ratio of soluble collagen to insoluble collagen is between about 1:3 to 3:1.
27. The filler material of claim 23 in the form of a rod, strip, film or sheet.
28. The filler material of claim 23 wherein the solid component is freeze dried.
29. The filler material of claim 23 wherein the solid component comprises a low melting polymer.
30. The filler material of claim 29 which further comprises a plasticizer.
31. The filler material of claim 30 wherein the plasticizer is a polysaccharide.
32. The filler material of claim 29 wherein the polymer is a copolymer of polyhydroxybuteric acid and valeric acid.
33. The filler material of claim 23 further comprising an energy absorption aid coated thereon.
34. The filler material of claim 33 wherein the energy absorbing aid is a dye.
35. The filler material of claim 33 wherein the energy absorbing aid is blood.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US654,860 | 1984-09-25 | ||
US07/654,860 US5156613A (en) | 1991-02-13 | 1991-02-13 | Collagen welding rod material for use in tissue welding |
US83217192A | 1992-02-06 | 1992-02-06 | |
US832,171 | 1992-02-06 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2103727A1 true CA2103727A1 (en) | 1992-08-14 |
Family
ID=27096836
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002103727A Abandoned CA2103727A1 (en) | 1991-02-13 | 1992-02-12 | Filler material for use in tissue welding |
Country Status (6)
Country | Link |
---|---|
US (1) | US5824015A (en) |
EP (1) | EP0572526A4 (en) |
JP (1) | JPH06505656A (en) |
AU (1) | AU1444292A (en) |
CA (1) | CA2103727A1 (en) |
WO (1) | WO1992014513A1 (en) |
Families Citing this family (139)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5690675A (en) * | 1991-02-13 | 1997-11-25 | Fusion Medical Technologies, Inc. | Methods for sealing of staples and other fasteners in tissue |
AU711199B2 (en) * | 1995-01-20 | 1999-10-07 | Macquarie Research Limited | Method of tissue repair |
AUPN066795A0 (en) * | 1995-01-20 | 1995-02-16 | Macquarie Research Limited | Method of repair |
US6217585B1 (en) | 1996-08-16 | 2001-04-17 | Converge Medical, Inc. | Mechanical stent and graft delivery system |
US5989276A (en) * | 1996-11-08 | 1999-11-23 | Advanced Bypass Technologies, Inc. | Percutaneous bypass graft and securing system |
US6293955B1 (en) | 1996-09-20 | 2001-09-25 | Converge Medical, Inc. | Percutaneous bypass graft and securing system |
US6743248B2 (en) | 1996-12-18 | 2004-06-01 | Neomend, Inc. | Pretreatment method for enhancing tissue adhesion |
EP1018983A4 (en) * | 1997-02-07 | 2006-09-27 | Providence Health Sys Oregon | Method of producing biomaterials |
AU767057B2 (en) * | 1997-02-07 | 2003-10-30 | Kenton W. Gregory | Method of producing biomaterials |
US20030191496A1 (en) | 1997-03-12 | 2003-10-09 | Neomend, Inc. | Vascular sealing device with microwave antenna |
US6371975B2 (en) | 1998-11-06 | 2002-04-16 | Neomend, Inc. | Compositions, systems, and methods for creating in situ, chemically cross-linked, mechanical barriers |
US5972007A (en) * | 1997-10-31 | 1999-10-26 | Ethicon Endo-Surgery, Inc. | Energy-base method applied to prosthetics for repairing tissue defects |
US6004333A (en) * | 1997-10-31 | 1999-12-21 | Ethicon Endo-Surgery, Inc. | Prosthetic with collagen for tissue repair |
US6221068B1 (en) * | 1998-01-15 | 2001-04-24 | Northwestern University | Method for welding tissue |
US6348679B1 (en) | 1998-03-17 | 2002-02-19 | Ameritherm, Inc. | RF active compositions for use in adhesion, bonding and coating |
US6361559B1 (en) | 1998-06-10 | 2002-03-26 | Converge Medical, Inc. | Thermal securing anastomosis systems |
EP1105167A1 (en) * | 1998-08-21 | 2001-06-13 | Tissuemed Limited | Activatable sheet for topical, therapeutic use |
US6458147B1 (en) * | 1998-11-06 | 2002-10-01 | Neomend, Inc. | Compositions, systems, and methods for arresting or controlling bleeding or fluid leakage in body tissue |
US6994686B2 (en) | 1998-08-26 | 2006-02-07 | Neomend, Inc. | Systems for applying cross-linked mechanical barriers |
US6899889B1 (en) | 1998-11-06 | 2005-05-31 | Neomend, Inc. | Biocompatible material composition adaptable to diverse therapeutic indications |
US6830756B2 (en) * | 1998-11-06 | 2004-12-14 | Neomend, Inc. | Systems, methods, and compositions for achieving closure of vascular puncture sites |
US7279001B2 (en) * | 1998-11-06 | 2007-10-09 | Neomend, Inc. | Systems, methods, and compositions for achieving closure of vascular puncture sites |
US6949114B2 (en) | 1998-11-06 | 2005-09-27 | Neomend, Inc. | Systems, methods, and compositions for achieving closure of vascular puncture sites |
US6310036B1 (en) | 1999-01-09 | 2001-10-30 | Last Chance Tissue Adhesives Corporation | High strength, Bio-compatible tissue adhesive and methods for treating vigorously bleeding surfaces |
US6287344B1 (en) | 1999-03-31 | 2001-09-11 | Ethicon Endo-Surgery, Inc. | Method for repairing tissue defects using an ultrasonic device |
US6251110B1 (en) | 1999-03-31 | 2001-06-26 | Ethicon Endo-Surgery, Inc. | Combined radio frequency and ultrasonic surgical device |
US6416486B1 (en) | 1999-03-31 | 2002-07-09 | Ethicon Endo-Surgery, Inc. | Ultrasonic surgical device having an embedding surface and a coagulating surface |
US6257241B1 (en) | 1999-03-31 | 2001-07-10 | Ethicon Endo-Surgery, Inc. | Method for repairing tissue defects using ultrasonic radio frequency energy |
US20050154406A1 (en) | 1999-07-28 | 2005-07-14 | Cardica, Inc. | Method for anastomosing vessels |
US6391038B2 (en) | 1999-07-28 | 2002-05-21 | Cardica, Inc. | Anastomosis system and method for controlling a tissue site |
US7682368B1 (en) | 1999-07-28 | 2010-03-23 | Cardica, Inc. | Anastomosis tool actuated with stored energy |
US7766924B1 (en) | 1999-07-28 | 2010-08-03 | Cardica, Inc. | System for performing anastomosis |
US7300444B1 (en) | 1999-07-28 | 2007-11-27 | Cardica, Inc. | Surgical system and method for connecting hollow tissue structures |
US7850703B2 (en) | 1999-07-28 | 2010-12-14 | Cardica, Inc. | System for performing anastomosis |
US6494889B1 (en) | 1999-09-01 | 2002-12-17 | Converge Medical, Inc. | Additional sutureless anastomosis embodiments |
US20020173809A1 (en) * | 1999-09-01 | 2002-11-21 | Fleischman Sidney D. | Sutureless anastomosis system deployment concepts |
US6649888B2 (en) | 1999-09-23 | 2003-11-18 | Codaco, Inc. | Radio frequency (RF) heating system |
US6391049B1 (en) | 1999-10-06 | 2002-05-21 | Board Of Regents The University Of Texas System | Solid biodegradable device for use in tissue repair |
US20050240170A1 (en) * | 1999-10-25 | 2005-10-27 | Therus Corporation | Insertable ultrasound probes, systems, and methods for thermal therapy |
CA2387127A1 (en) | 1999-10-25 | 2001-05-17 | Therus Corporation | Use of focused ultrasound for vascular sealing |
GB9925380D0 (en) * | 1999-10-28 | 1999-12-29 | Tissuemed Ltd | Flexible sheets for use in therapy |
US6626855B1 (en) | 1999-11-26 | 2003-09-30 | Therus Corpoation | Controlled high efficiency lesion formation using high intensity ultrasound |
US20040068278A1 (en) * | 1999-12-06 | 2004-04-08 | Converge Medical Inc. | Anastomosis systems |
AU2598201A (en) * | 1999-12-23 | 2001-07-03 | Therus Corporation | Ultrasound transducers for imaging and therapy |
US6607522B1 (en) * | 2000-03-16 | 2003-08-19 | General Hospital Corporation | Methods for tissue welding using laser-activated protein solders |
US6902564B2 (en) * | 2001-08-15 | 2005-06-07 | Roy E. Morgan | Methods and devices for electrosurgery |
US20040167244A1 (en) * | 2000-08-18 | 2004-08-26 | Auge Wayne K. | Methods and compositions for fusing bone during endoscopy procedures |
US7819861B2 (en) * | 2001-05-26 | 2010-10-26 | Nuortho Surgical, Inc. | Methods for electrosurgical electrolysis |
US6547794B2 (en) * | 2000-08-18 | 2003-04-15 | Auge', Ii Wayne K. | Method for fusing bone during endoscopy procedures |
US7445619B2 (en) * | 2000-08-18 | 2008-11-04 | Map Technologies Llc | Devices for electrosurgery |
US7771422B2 (en) | 2002-06-06 | 2010-08-10 | Nuortho Surgical, Inc. | Methods and devices for electrosurgery |
US6296607B1 (en) * | 2000-10-20 | 2001-10-02 | Praxis, Llc. | In situ bulking device |
WO2002069813A2 (en) | 2001-02-05 | 2002-09-12 | A-Med Systems, Inc. | Anastomosis system and related methods |
US7066932B1 (en) | 2001-05-26 | 2006-06-27 | Map Technologies Llc | Biologically enhanced irrigants |
US6972023B2 (en) * | 2001-07-05 | 2005-12-06 | Converge Medical, Inc. | Distal anastomosis system |
US20060064119A9 (en) * | 2001-07-05 | 2006-03-23 | Converge Medical, Inc. | Vascular anastomosis systems |
US6626920B2 (en) | 2001-07-05 | 2003-09-30 | Converge Medical, Inc. | Distal anastomosis system |
US6858035B2 (en) | 2001-07-05 | 2005-02-22 | Converge Medical, Inc. | Distal anastomosis system |
US20030229365A1 (en) * | 2002-06-10 | 2003-12-11 | Whayne James G. | Angled vascular anastomosis system |
US6613348B1 (en) * | 2001-07-31 | 2003-09-02 | Manoj K. Jain | Process of controlling absorbency in collagen flakes |
US8734441B2 (en) | 2001-08-15 | 2014-05-27 | Nuortho Surgical, Inc. | Interfacing media manipulation with non-ablation radiofrequency energy system and method |
US8235979B2 (en) | 2001-08-15 | 2012-08-07 | Nuortho Surgical, Inc. | Interfacing media manipulation with non-ablation radiofrequency energy system and method |
US8591508B2 (en) * | 2001-08-15 | 2013-11-26 | Nuortho Surgical, Inc. | Electrosurgical plenum |
EP1437975B1 (en) | 2001-09-26 | 2011-08-10 | Rice University | Optically-absorbing nanoparticles for enhanced tissue repair |
US6773699B1 (en) | 2001-10-09 | 2004-08-10 | Tissue Adhesive Technologies, Inc. | Light energized tissue adhesive conformal patch |
US6939364B1 (en) | 2001-10-09 | 2005-09-06 | Tissue Adhesive Technologies, Inc. | Composite tissue adhesive |
US6780840B1 (en) | 2001-10-09 | 2004-08-24 | Tissue Adhesive Technologies, Inc. | Method for making a light energized tissue adhesive |
US6875427B1 (en) | 2001-10-09 | 2005-04-05 | Tissue Adhesive Technologies, Inc. | Light energized tissue adhesive |
US7923431B2 (en) | 2001-12-21 | 2011-04-12 | Ferrosan Medical Devices A/S | Haemostatic kit, a method of preparing a haemostatic agent and a method of promoting haemostatis |
US7238195B2 (en) | 2002-05-10 | 2007-07-03 | Tyco Healthcare Group Lp | Wound closure material applicator and stapler |
US7967839B2 (en) * | 2002-05-20 | 2011-06-28 | Rocky Mountain Biosystems, Inc. | Electromagnetic treatment of tissues and cells |
EP2228018B1 (en) | 2002-06-17 | 2012-05-09 | Tyco Healthcare Group LP | Annular support structures |
WO2004014217A2 (en) * | 2002-08-09 | 2004-02-19 | Marchitto, Kevin | Activated surgical fasteners, devices therefor and uses thereof |
PL377477A1 (en) | 2002-12-11 | 2006-02-06 | Ferrosan A/S | Gelatine-based materials as swabs |
US7257450B2 (en) | 2003-02-13 | 2007-08-14 | Coaptus Medical Corporation | Systems and methods for securing cardiovascular tissue |
US8021359B2 (en) | 2003-02-13 | 2011-09-20 | Coaptus Medical Corporation | Transseptal closure of a patent foramen ovale and other cardiac defects |
CA2519636A1 (en) | 2003-03-27 | 2004-10-14 | Cierra, Inc. | Methods and apparatus for treatment of patent foramen ovale |
US7186251B2 (en) | 2003-03-27 | 2007-03-06 | Cierra, Inc. | Energy based devices and methods for treatment of patent foramen ovale |
US7293562B2 (en) | 2003-03-27 | 2007-11-13 | Cierra, Inc. | Energy based devices and methods for treatment of anatomic tissue defects |
US7165552B2 (en) | 2003-03-27 | 2007-01-23 | Cierra, Inc. | Methods and apparatus for treatment of patent foramen ovale |
US6939348B2 (en) | 2003-03-27 | 2005-09-06 | Cierra, Inc. | Energy based devices and methods for treatment of patent foramen ovale |
US7972330B2 (en) | 2003-03-27 | 2011-07-05 | Terumo Kabushiki Kaisha | Methods and apparatus for closing a layered tissue defect |
US8021362B2 (en) | 2003-03-27 | 2011-09-20 | Terumo Kabushiki Kaisha | Methods and apparatus for closing a layered tissue defect |
US7311701B2 (en) | 2003-06-10 | 2007-12-25 | Cierra, Inc. | Methods and apparatus for non-invasively treating atrial fibrillation using high intensity focused ultrasound |
AR054637A1 (en) | 2004-01-30 | 2007-07-11 | Ferrosan As | AEROSOLS AND HEMOSTATIC COMPOSITIONS |
US7367975B2 (en) | 2004-06-21 | 2008-05-06 | Cierra, Inc. | Energy based devices and methods for treatment of anatomic tissue defects |
EP1786480B1 (en) | 2004-07-09 | 2016-09-21 | Ferrosan Medical Devices A/S | Haemostatic composition comprising hyaluronic acid |
US7473252B2 (en) | 2004-10-07 | 2009-01-06 | Coaptus Medical Corporation | Systems and methods for shrinking and/or securing cardiovascular tissue |
US7717313B2 (en) * | 2004-10-18 | 2010-05-18 | Tyco Healthcare Group Lp | Surgical apparatus and structure for applying sprayable wound treatment material |
US7845536B2 (en) | 2004-10-18 | 2010-12-07 | Tyco Healthcare Group Lp | Annular adhesive structure |
EP1804685B1 (en) | 2004-10-18 | 2016-07-27 | Covidien LP | Extraluminal sealant applicator |
AU2005301150B2 (en) * | 2004-10-18 | 2011-02-03 | Covidien Lp | Apparatus for applying wound treatment material using tissue-penetrating needles |
US7455682B2 (en) * | 2004-10-18 | 2008-11-25 | Tyco Healthcare Group Lp | Structure containing wound treatment material |
CA2584019C (en) * | 2004-10-18 | 2014-09-16 | Tyco Healthcare Group Lp | Structure for applying sprayable wound treatment material |
US7938307B2 (en) | 2004-10-18 | 2011-05-10 | Tyco Healthcare Group Lp | Support structures and methods of using the same |
US8109274B2 (en) | 2005-04-11 | 2012-02-07 | Terumo Kabushiki Kaisha | Methods and electrode apparatus to achieve a closure of a layered tissue defect |
WO2007035726A2 (en) * | 2005-09-19 | 2007-03-29 | Mayo Foundation For Medical Education And Research | Implantable closure apparatus and methods |
US20070233185A1 (en) | 2005-10-20 | 2007-10-04 | Thomas Anderson | Systems and methods for sealing a vascular opening |
CA2684864A1 (en) | 2007-04-06 | 2008-10-16 | Stephen Flock | Inductive heating of tissues using alternating magnetic fields and uses thereof |
US10441346B2 (en) | 2007-04-06 | 2019-10-15 | Rocky Mountain Biosystems, Inc | Inductive heating of tissues using alternating magnetic fields and uses thereof |
WO2008143955A2 (en) * | 2007-05-14 | 2008-11-27 | The Regents Of The University Of Colorado | Laser fusion of tissue layers |
US7979108B2 (en) * | 2007-08-27 | 2011-07-12 | William Harrison Zurn | Automated vessel repair system, devices and methods |
US9168039B1 (en) | 2007-09-06 | 2015-10-27 | Cardica, Inc. | Surgical stapler with staples of different sizes |
US8070036B1 (en) | 2007-09-06 | 2011-12-06 | Cardica, Inc | True multi-fire surgical stapler configured to fire staples of different sizes |
US7988026B2 (en) | 2007-09-06 | 2011-08-02 | Cardica, Inc. | Endocutter with staple feed |
WO2009109194A2 (en) | 2008-02-29 | 2009-09-11 | Ferrosan A/S | Device for promotion of hemostasis and/or wound healing |
US7886951B2 (en) * | 2008-11-24 | 2011-02-15 | Tyco Healthcare Group Lp | Pouch used to deliver medication when ruptured |
US9532827B2 (en) | 2009-06-17 | 2017-01-03 | Nuortho Surgical Inc. | Connection of a bipolar electrosurgical hand piece to a monopolar output of an electrosurgical generator |
US8517962B2 (en) | 2009-10-12 | 2013-08-27 | Kona Medical, Inc. | Energetic modulation of nerves |
US8986231B2 (en) | 2009-10-12 | 2015-03-24 | Kona Medical, Inc. | Energetic modulation of nerves |
US8295912B2 (en) | 2009-10-12 | 2012-10-23 | Kona Medical, Inc. | Method and system to inhibit a function of a nerve traveling with an artery |
US9174065B2 (en) | 2009-10-12 | 2015-11-03 | Kona Medical, Inc. | Energetic modulation of nerves |
US8986211B2 (en) | 2009-10-12 | 2015-03-24 | Kona Medical, Inc. | Energetic modulation of nerves |
US9119951B2 (en) | 2009-10-12 | 2015-09-01 | Kona Medical, Inc. | Energetic modulation of nerves |
US8469904B2 (en) | 2009-10-12 | 2013-06-25 | Kona Medical, Inc. | Energetic modulation of nerves |
US20110118600A1 (en) | 2009-11-16 | 2011-05-19 | Michael Gertner | External Autonomic Modulation |
US20110092880A1 (en) | 2009-10-12 | 2011-04-21 | Michael Gertner | Energetic modulation of nerves |
US20160059044A1 (en) | 2009-10-12 | 2016-03-03 | Kona Medical, Inc. | Energy delivery to intraparenchymal regions of the kidney to treat hypertension |
US8617157B2 (en) | 2010-01-26 | 2013-12-31 | Covidien Lp | Hernia repair system |
US8388613B1 (en) | 2010-04-09 | 2013-03-05 | The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration | Methods and apparatus for microwave tissue welding for wound closure |
DE102010020664A1 (en) * | 2010-05-05 | 2011-11-10 | Aesculap Ag | Surgical system for connecting body tissue parts |
US9408658B2 (en) | 2011-02-24 | 2016-08-09 | Nuortho Surgical, Inc. | System and method for a physiochemical scalpel to eliminate biologic tissue over-resection and induce tissue healing |
US8663209B2 (en) | 2012-01-24 | 2014-03-04 | William Harrison Zurn | Vessel clearing apparatus, devices and methods |
JP6241624B2 (en) | 2012-03-06 | 2017-12-06 | フェロサン メディカル デバイシーズ エイ/エス | Pressurized container containing hemostatic paste |
JP6394916B2 (en) | 2012-06-12 | 2018-09-26 | フェロサン メディカル デバイシーズ エイ/エス | Dry hemostatic composition |
US9833207B2 (en) | 2012-08-08 | 2017-12-05 | William Harrison Zurn | Analysis and clearing module, system and method |
US9522002B2 (en) | 2012-12-13 | 2016-12-20 | Covidien Lp | Surgical instrument with pressure distribution device |
US9579142B1 (en) | 2012-12-13 | 2017-02-28 | Nuortho Surgical Inc. | Multi-function RF-probe with dual electrode positioning |
US9962533B2 (en) | 2013-02-14 | 2018-05-08 | William Harrison Zurn | Module for treatment of medical conditions; system for making module and methods of making module |
AU2014283170B2 (en) | 2013-06-21 | 2017-11-02 | Ferrosan Medical Devices A/S | Vacuum expanded dry composition and syringe for retaining same |
US10028731B2 (en) | 2013-11-12 | 2018-07-24 | Genzyme Corporation | Barrier application device |
CA2928963C (en) | 2013-12-11 | 2020-10-27 | Ferrosan Medical Devices A/S | Dry composition comprising an extrusion enhancer |
JP6726852B2 (en) | 2014-10-13 | 2020-07-22 | フェッローサン メディカル ディバイス エー/エス | Dry composition for use in hemostasis and wound healing |
US10925579B2 (en) | 2014-11-05 | 2021-02-23 | Otsuka Medical Devices Co., Ltd. | Systems and methods for real-time tracking of a target tissue using imaging before and during therapy delivery |
JP6747650B2 (en) | 2014-12-24 | 2020-08-26 | フェロサン メディカル デバイシーズ エイ/エス | Syringe for holding and mixing the first substance and the second substance |
CA2986981A1 (en) | 2015-07-03 | 2017-01-12 | Ferrosan Medical Devices A/S | Syringe for mixing two components and for retaining a vacuum in a storage condition |
US11696929B2 (en) | 2017-09-20 | 2023-07-11 | The Regents Of The University Of California | Methods and systems for conserving highly expanded cells |
JP7395113B2 (en) | 2018-05-09 | 2023-12-11 | フェロサン メディカル デバイシーズ エイ/エス | Method of preparing a hemostatic composition |
WO2022010904A1 (en) * | 2020-07-06 | 2022-01-13 | The Regents Of The University Of California | Melt-and-meld approach to repair tissue defects |
Family Cites Families (61)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2011169A (en) * | 1932-04-13 | 1935-08-13 | Wappler Frederick Charles | Forcipated surgical electrode |
US2510205A (en) * | 1949-02-11 | 1950-06-06 | Linde Air Prod Co | Inert-gas shielded continuous-feed metal-arc welding apparatus |
US2618267A (en) * | 1949-03-11 | 1952-11-18 | Hanriot Raymond | Control means for electrosurgical cutting instruments |
US2708933A (en) * | 1951-05-17 | 1955-05-24 | August William | Gas blanketed electro-surgical device |
US2808833A (en) * | 1952-12-06 | 1957-10-08 | Birtcher Corp | Gas blanketed clotting instrument |
US3527224A (en) * | 1967-09-05 | 1970-09-08 | American Cyanamid Co | Method of surgically bonding tissue together |
US3903891A (en) * | 1968-01-12 | 1975-09-09 | Hogle Kearns Int | Method and apparatus for generating plasma |
US3578939A (en) * | 1968-10-15 | 1971-05-18 | Randolph E Green | Backing gas attachment saving device for heliarc welding |
US3742955A (en) * | 1970-09-29 | 1973-07-03 | Fmc Corp | Fibrous collagen derived product having hemostatic and wound binding properties |
US3858586A (en) * | 1971-03-11 | 1975-01-07 | Martin Lessen | Surgical method and electrode therefor |
US3834392A (en) * | 1973-02-01 | 1974-09-10 | Kli Inc | Laparoscopy system |
US3991764A (en) * | 1973-11-28 | 1976-11-16 | Purdue Research Foundation | Plasma arc scalpel |
US4100390A (en) * | 1975-11-17 | 1978-07-11 | Arcstart, Inc. | Control means for tig type torches and the like |
US4040426A (en) * | 1976-01-16 | 1977-08-09 | Valleylab, Inc. | Electrosurgical method and apparatus for initiating an electrical discharge in an inert gas flow |
US4060088A (en) * | 1976-01-16 | 1977-11-29 | Valleylab, Inc. | Electrosurgical method and apparatus for establishing an electrical discharge in an inert gas flow |
SU1091933A1 (en) * | 1981-10-14 | 1984-05-15 | Рижский Медицинский Институт | Method of connecting vessels |
JPS6055925A (en) * | 1983-09-05 | 1985-04-01 | オリンパス光学工業株式会社 | Noise preventing device of electronic scope |
US5002051A (en) * | 1983-10-06 | 1991-03-26 | Lasery Surgery Software, Inc. | Method for closing tissue wounds using radiative energy beams |
US4672969A (en) * | 1983-10-06 | 1987-06-16 | Sonomo Corporation | Laser healing method |
US4854320A (en) * | 1983-10-06 | 1989-08-08 | Laser Surgery Software, Inc. | Laser healing method and apparatus |
US5140984A (en) * | 1983-10-06 | 1992-08-25 | Proclosure, Inc. | Laser healing method and apparatus |
IL75998A0 (en) * | 1984-08-07 | 1985-12-31 | Medical Laser Research & Dev C | Laser system for providing target tissue specific energy deposition |
US4889120A (en) * | 1984-11-13 | 1989-12-26 | Gordon Robert T | Method for the connection of biological structures |
US4638800A (en) * | 1985-02-08 | 1987-01-27 | Research Physics, Inc | Laser beam surgical system |
US4708137A (en) * | 1985-05-20 | 1987-11-24 | Olympus Optical Co., Ltd. | High-frequency incision device |
US4633870A (en) * | 1985-06-26 | 1987-01-06 | Sauer Jude S | Apparatus for effecting anastomosis of tubular tissue by laser welding |
US4892098A (en) * | 1985-06-26 | 1990-01-09 | Sauer Jude S | Tubular tissue welding device without moving parts |
US4640279A (en) * | 1985-08-08 | 1987-02-03 | Oximetrix, Inc. | Combination surgical scalpel and electrosurgical instrument |
US4901720A (en) * | 1986-04-08 | 1990-02-20 | C. R. Bard, Inc. | Power control for beam-type electrosurgical unit |
US4781175A (en) * | 1986-04-08 | 1988-11-01 | C. R. Bard, Inc. | Electrosurgical conductive gas stream technique of achieving improved eschar for coagulation |
US4943290A (en) * | 1987-06-23 | 1990-07-24 | Concept Inc. | Electrolyte purging electrode tip |
US4878492A (en) * | 1987-10-08 | 1989-11-07 | C. R. Bard, Inc. | Laser balloon catheter |
US4930504A (en) * | 1987-11-13 | 1990-06-05 | Diamantopoulos Costas A | Device for biostimulation of tissue and method for treatment of tissue |
US5201745A (en) * | 1988-03-15 | 1993-04-13 | Imedex | Visceral surgery patch |
US4929246A (en) * | 1988-10-27 | 1990-05-29 | C. R. Bard, Inc. | Method for closing and sealing an artery after removing a catheter |
US5021452A (en) * | 1989-01-09 | 1991-06-04 | The Board Of Regents Of The University Of Washington | Process for enhancing wound healing |
IT216721Z2 (en) * | 1989-06-30 | 1991-09-19 | Euroresearch S R L Milano | TUTOR CONSTITUTED BY A HETEROLOGICAL COLLAGEN TUBULAR, SUITABLE FOR USE IN THE SUTURE OF CABLE ORGANS. |
US5041110A (en) * | 1989-07-10 | 1991-08-20 | Beacon Laboratories, Inc. | Cart for mobilizing and interfacing use of an electrosurgical generator and inert gas supply |
WO1991004073A1 (en) * | 1989-09-12 | 1991-04-04 | The Trustees Of Columbia University In The City Of New York | Laser tissue welding with dye enhanced solders |
US5071417A (en) * | 1990-06-15 | 1991-12-10 | Rare Earth Medical Lasers, Inc. | Laser fusion of biological materials |
US5209776A (en) * | 1990-07-27 | 1993-05-11 | The Trustees Of Columbia University In The City Of New York | Tissue bonding and sealing composition and method of using the same |
US5292362A (en) * | 1990-07-27 | 1994-03-08 | The Trustees Of Columbia University In The City Of New York | Tissue bonding and sealing composition and method of using the same |
CA2052196A1 (en) * | 1990-10-11 | 1992-04-12 | Jude S. Sauer | Clamp for approximating tissue sections |
US5410016A (en) * | 1990-10-15 | 1995-04-25 | Board Of Regents, The University Of Texas System | Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers |
US5219895A (en) * | 1991-01-29 | 1993-06-15 | Autogenesis Technologies, Inc. | Collagen-based adhesives and sealants and methods of preparation and use thereof |
JPH04288165A (en) * | 1991-03-18 | 1992-10-13 | Terumo Corp | Organ implant and manufacture thereof |
CA2071137A1 (en) * | 1991-07-10 | 1993-01-11 | Clarence C. Lee | Composition and method for revitalizing scar tissue |
WO1993003793A1 (en) * | 1991-08-22 | 1993-03-04 | Roberto Enzo Di Biaggio | Medical light treatment apparatus |
US5272716A (en) * | 1991-10-15 | 1993-12-21 | Mcdonnell Douglas Corporation | Hand held laser apparatus |
US5207691A (en) * | 1991-11-01 | 1993-05-04 | Medical Scientific, Inc. | Electrosurgical clip applicator |
CA2117588C (en) * | 1992-02-28 | 1998-08-25 | Jeffrey A. Hubbell | Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers |
US5290272A (en) * | 1992-03-16 | 1994-03-01 | Helios Inc. | Method for the joining of ocular tissues using laser light |
US5372585A (en) * | 1992-04-09 | 1994-12-13 | Tiefenbrun; Jonathan | Instrument and associated method for applying biologically effective composition during laparoscopic operation |
US5334191A (en) * | 1992-05-21 | 1994-08-02 | Dix Phillip Poppas | Laser tissue welding control system |
US5292253A (en) * | 1992-06-22 | 1994-03-08 | Laser Medical Technology, Inc. | Method for repairing tooth and bone tissue |
US5336221A (en) * | 1992-10-14 | 1994-08-09 | Premier Laser Systems, Inc. | Method and apparatus for applying thermal energy to tissue using a clamp |
US5354323A (en) * | 1992-10-20 | 1994-10-11 | Premier Laser Systems, Inc. | Optical heating system |
US5403312A (en) * | 1993-07-22 | 1995-04-04 | Ethicon, Inc. | Electrosurgical hemostatic device |
US5330974A (en) * | 1993-03-01 | 1994-07-19 | Fibratek, Inc. | Therapeutic fibrinogen compositions |
GR940100335A (en) * | 1993-07-22 | 1996-05-22 | Ethicon Inc. | Electrosurgical device for placing staples. |
US5421923A (en) * | 1993-12-03 | 1995-06-06 | Baxter International, Inc. | Ultrasonic welding horn with sonics dampening insert |
-
1992
- 1992-02-12 CA CA002103727A patent/CA2103727A1/en not_active Abandoned
- 1992-02-12 JP JP4506770A patent/JPH06505656A/en active Pending
- 1992-02-12 AU AU14442/92A patent/AU1444292A/en not_active Abandoned
- 1992-02-12 WO PCT/US1992/001154 patent/WO1992014513A1/en not_active Application Discontinuation
- 1992-02-12 EP EP92907093A patent/EP0572526A4/en not_active Withdrawn
-
1995
- 1995-06-05 US US08/461,227 patent/US5824015A/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
WO1992014513A1 (en) | 1992-09-03 |
EP0572526A1 (en) | 1993-12-08 |
EP0572526A4 (en) | 1995-12-06 |
JPH06505656A (en) | 1994-06-30 |
US5824015A (en) | 1998-10-20 |
AU1444292A (en) | 1992-09-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5824015A (en) | Method for welding biological tissue | |
US5669934A (en) | Methods for joining tissue by applying radiofrequency energy to performed collagen films and sheets | |
US5156613A (en) | Collagen welding rod material for use in tissue welding | |
US5209776A (en) | Tissue bonding and sealing composition and method of using the same | |
EP0542880B1 (en) | Tissue bonding and sealing composition and method of using the same | |
US7078378B1 (en) | Method of tissue repair II | |
US6939364B1 (en) | Composite tissue adhesive | |
US6773699B1 (en) | Light energized tissue adhesive conformal patch | |
IL95664A (en) | Dye enhanced biologically active compatible tissue soldering compositions and method of ex vivo welding tissues therewith | |
Talmor et al. | Laser tissue welding: a biotechnological advance for the future | |
US6780840B1 (en) | Method for making a light energized tissue adhesive | |
Bleustein et al. | Semi‐solid albumin solder improved mechanical properties for laser tissue welding | |
US6875427B1 (en) | Light energized tissue adhesive | |
Kopchok et al. | Thermal studies of in-vivo vascular tissue fusion by argon laser | |
Self et al. | Limited thrombogenicity of low temperature, laser‐welded vascular anastomoses | |
USRE43134E1 (en) | Biocompatible denatured albumin lamina | |
Samonte et al. | Laser‐assisted microvascular anastomosis using CO2 and KTP/532 lasers | |
Bass et al. | Soldering is a superior alternative to fibrin sealant | |
Bass et al. | Laparoscopic applications of laser-activated tissue glues | |
Shohet et al. | Prevention of pharyngocutaneous fistulas by means of laser‐weld techniques | |
Chan et al. | Laser assisted soldering: Effects of hydration on solder-tissue adhesion | |
AU768533C (en) | Method of tissue repair II | |
OZ et al. | Laser-assisted fibrinogen bonding of umbilical vein grafts | |
Libutti et al. | Dye-enhanced tissue welding using fibrinogen and continuous-wave argon lasers | |
Al-Jarrah et al. | Tissue Welding Using (800±10nm) Diode and (1064nm) Nd: YAG Lasers |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FZDE | Discontinued | ||
FZDE | Discontinued |
Effective date: 20000214 |