Classifications

• • 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
  • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
  • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
  • A61L27/3839—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by the site of application in the body
• • 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
  • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
  • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
  • A61L2/0082—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using chemical substances
• • 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
  • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
  • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• • 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
  • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
  • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
  • A61L27/362—Skin, e.g. dermal papillae
• • 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
  • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
  • A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
  • A61L27/3687—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
• • 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
  • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
  • A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
  • A61L27/3691—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
• • 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
  • A61L2430/00—Materials or treatment for tissue regeneration
  • A61L2430/40—Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking

Definitions

• This invention is directed to a method for processing an organ, tissue, joint, and the like for use in transplantation, and to the tissue thereby produced.
• the method includes removing tissue from a donor, processing the tissue to remove all the cells, and processing of the collagen scaffold for storage.
• the method further includes repopulating the collagen scaffold through seeding with stem cells or other cells for implantation into a recipient in need thereof.
• Figure 1 depicts a schematic first step of the improved process disclosed herein.
• Figure 2 depicts a schematic of a second step of the improved process disclosed herein
• Figure 3 depicts a schematic of a third step of the improved process disclosed herein.
• Tissues to be processed by the present invention include, but are not limited to, tracheal tissue, heart valves, total joints, entire heart, vasculature, soft organs, and any other tissue required for implantation.
• the tissue processed by the method of the present invention is a heart.
• the tissue processed by the method of the present invention is a knee, shoulder, wrist, ankle, elbow or other joint. The recipient's joint is removed, due to illness or trauma, and the joint prepared according to this invention is implanted according to methods known in the art or which become known hereafter.
• the tissue to be treated is removed from a donor and processed to remove all the cells.
• the remaining collagen scaffold is then "seeded" with non-immunogenic cells including but not limited to stem cells, fetal cells and the like to repopulate the tissue before transplantation into a recipient.
• non-immunogenic cells including but not limited to stem cells, fetal cells and the like.
• different stem cells known in the art or which become known hereafter are selected such that appropriate tissues are formed upon implantation into a recipient of the seeded implant.
• a collagen structure is left completely (or nearly so) intact while all cells and cellular debris, lipids and non-collagenous proteins are thoroughly eliminated.
• a preferred process for use according to this invention is known as the BIOCLEANSE PROCESSTM, publication no. WO 00/29037. Applicants provide herein below (part II) further modifications and improvements to this novel process.
• the process can be used to treat autograft material ex vivo for reimplantation, so that tissues from different donors, whether animal or human, (allogenic or xenogenic), may be cleaned, sterilized and/or decellularized.
• the process utilizes rapid pressure cycling to achieve penetrating cleaning of tissues.
• the tissue may be processed for storage. Storage may come in the form of a bioreactor, cryopreservation, freezing, chilling, drying, room temperature packaging, or freeze-drying.
• U.S. Patent No. 5,336,616 and WO 99/41981 are incorporated herein by reference for disclosure on methods for cryopreservation, freezing and drying of collagen-based tissues.
• the remaining collagen scaffold is optionally seeded with non-immunogenic cells before implantation into a recipient.
• the "seeded" collagen scaffold is grown according to known organ perfusion technology. Methods of repopulating collagen-based tissue are disclosed in U.S. Patent 5,192,312; U.S. Patent 5,863,296 and WO99/60951, the disclosure of each of which is hereby incorporated herein by reference.
• One aspect of the present invention relates to a method of making a substantially intact collagen heart scaffold, which is made to order.
• a patient in need of a heart transplant upon receiving diagnosis, commissions production of a heart.
• a heart is removed from a cadaver.
• the harvested heart is then treated according to the method of this invention, wherein all cells, cellular debris, lipids and non-collagenous proteins are removed.
• the remaining collagen heart scaffold is seeded with stem cells, myocardial cells, growth factors and the like, and grown in an organ perfusion system. The result is a replacement heart ready for use in heart replacement surgery.
• the knee joint is a substantially cleaned portion of a femur, patella and tibia.
• a patient in need of knee replacement surgery commission production of a knee Upon commission, portions of the femur, patella and tibia are removed from a cadaver.
• the harvested tissue is then processed according to the method of the present invention, wherein all the cells, cellular debris, lipids and non-collagenous proteins are removed.
• the remaining collagen scaffold of the knee joint is seeded with cells and repopulated in an organ perfusion system.
• the result of the present method is a made-to-order replacement knee implant ready for implantation into a patient.
• the replacement joint may be directly implanted into a patient for in situ revitalization and remodeling.
• Another aspect of the present invention relates to a method of making a substantially intact transplantable trachea.
• a patient in need of tracheal replacement upon receiving diagnosis, commissions production of a new trachea according to the method of this invention.
• the necessary portion of the trachea is then removed from a cadaver and treated according to the method of the present invention.
• the trachea is cleaned to remove all cells, cellular debris, lipids and non-collagenous cells.
• the remaining collagen scaffold of the trachea is seeded with stem cells. After seeding, the collagen scaffold is processed in an organ perfusion system, wherein new cells are grown to repopulate the trachea. After processing according to the methods of this invention, the harvested trachea is ready for transplantation into a patient.
• the basic process described in WO 00/29037 is improved by incorporating and implementing the use of a simple single air piston device to provide both the air pressure and the vacuum necessary for the process.
• the process as described in WO 00/29037 preferably uses a sanitary air filtration system (which can be expensive due to the complex steam in place and integrity testing system required for clean air) and a valving system to provide clean air for preferably 100 psi pressure and another sanitary valving receiver and pump system to provide the vacuum.
• the valving receiver preferably comprises a large stainless steel tank with anti-foam and cleaning provisions. It is desirable to provide small inexpensive reaction chamber units that can be utilized for "no fluid mixing" single donor processing.
• Air pistons for incorporation into the current process of WO 00/29037 preferably would be commercially available, sanitary, pharmaceutical precision fitted pistons (e.g. Bosch pistons). With the use of an air piston, no large vacuum reservoir, no vacuum pump, and none of the associated sanitary valving would be necessary as disclosed in WO 00/29037 (specifically shown in Figure 3).
• the air pistons can also be set to process bone at a much faster rate.
• An air piston can go through a pressure/vacuum cycle five times a second, while older processes may require up to fifteen seconds to complete one vacuum/vacuum cycle (due to vacuum pump recovery time).
• Use of the subject air piston configuration would reduce the cycle time from 3 to 4 hours to half an hour per batch. The subject invention can achieve these reductions in cycle times while meeting and even exceeding sterile isolation guidelines followed in the industry.
• the previous process with its foaming reagents (e.g. hydrogen peroxide and the tissue lipids in combination), produces a thick viscous foam (e.g., up to 6.1 gallons of foam at 100 PSI). Since this foam is under pressure initially, it is then transferred to an 80% vacuum. When it accumulates in the vacuum reservoir it becomes very voluminous (6J gallons of foam at 100 PSI equates to about 227 gallons of foam at 80% vacuum). This voluminous foam is the primary reason that a series of small single donor reaction chambers would be difficult to connect to a common vacuum reservoir without cross contamination of fluids. If the voluminous foam from one donor chamber comes in contact with the port evacuating another donor chamber, it might be possible that cross contamination could occur.
• foaming reagents e.g. hydrogen peroxide and the tissue lipids in combination
• the subject invention does not create the semi-permanent voluminous foam sitting in a vacuum receiver; the foam that is created simply is compressed and uncompressed by the air piston. Furthermore, if one of the reagents of the process (e.g. hydrogen peroxide) creates too much foam, it is just vented through a pressure relief valve.
• one of the reagents of the process e.g. hydrogen peroxide
• FIG. 1-3 the improvement to the BIOCLEANSE described in WO 00/29037 process is shown implementing the air piston 110.
• the reaction chamber 120 and system is filled with chemical/reagent via the chemical feed 116 until fluid flows through valve 124. Valves 118 and 124 are open during the filling of the system.
• valves 124 and 118 are, closed and the piston 110 is drawn back by the air pressure multiplier 112.
• Reaction chamber 120 and Air piston 110 are connected via a conduit/line 128.
• a vacuum of 80% is created by movement of the piston 110, which may preferably occur upon application of 75 PSI pushing back on the piston 110.
• the piston 110 is pushed forward via the Air pressure multiplier 112 to produce pressure in the reaction chamber (preferably 100 PSI) as shown in Figure 3. Steps 2 and 3 are repeated as often and as quickly as desired.
• a pressure relief valve 126 is provided in the system to relieve pressure and to purge foam if necessary.
• Filter 122 is provided along the fluid line of the system to filter debris and other particulate matter.
• Filter 114 is provided to filter air in or out, as desired, of the piston 110.
• tissue as used herein includes, but is not limited to, bone, neural tissue, fibrous connective tissue including tendons and ligaments, cartilage, dura, pericardia, muscle, heart valves, veins and arteries and other vasculature, dermis, adipose tissue, or glandular tissue.
• Antimicrobial agents” and/or “viral inactivating agents” as used herein include, but are not limited to benzalkonium chloride, benzethonium chloride, methylbenzethonium chloride, and cetylpyridinium chloride, hydrogen peroxide, calcium hydroxide, quaternary ammonium compounds, and other such similar compounds as disclosed, e.g., in U.S. Patent Nos. 6,224,579; 6,175,053; and 5,994,383. Benzalkonium chloride, hydrogen peroxide and calcium hydroxide are preferred agents.
• MATERIALS All materials/equipment shall be autociaved, irradiated, or sterile filtered, using approved procedures.
• Sections of dermis tissue ⁇ 0J mm in thickness will be placed back into the procurement containers. Place the containers into two poly bags; tie a knot in each bag individually to seal close the open end. Return the containers to freezer. Label appropriately.
• the dermis tissue >0J-mm in thickness will be placed into a graduated cylinder. Ensure that the tissue is lightly tamped. This is to ensure that the tissue has settled. The tissue once settled has . to be below the highest graduation. If it is not then, procure a larger graduated cylinder, transfer tissue to new graduated cylinder and the measure the volume of tissue.
• 4.1.2 Record the clean room temperature using a calibrated thermometer. Record the temperature on Attachment A. The temperature is to be between 19-38°C.
• the dermis tissue is to be left in the 1% benzalkonium chloride solution at 4° ⁇ 2°C for a period of 1-24 hours.
• 6.1.16 Record the fluid volume, lot # of the 1% tween-20 + 0.5% hydrogen peroxide solution and associated expiration date, chemical manufacturer, and start time on Attachment A. 6.1.17 Place the sonic container in sonic for 14 ⁇ 1 minutes.
• 6.1.21 Remove the sonic container from the sonic device. 6.1.22 Turn off the sonic until the tissue is ready to go back into the sonic. 6.1.23 Record the temperature of the water bath on Attachment A. If the temperature is >26° C, then drain and replace the sonic water. 6.1.24 Change gloves prior to touching any tissue after working with the sonic and thermometer.
• 7.1.36 Change gloves prior to touching any equipment that comes in contact with tissue after working with the sonic and thermometer.
• 7.1.37 Pour the solution with the dermis into a sieve over a sink or dump bucket.
• 9.1.42 Place the dermis in the sonic container. Fill with at least 10 times the minimum volume of the tissue with purified water on the dermis and gently agitate using a swirling motion for 4 ⁇ 1 minutes. (See attachment A for minimum predetermined volume.) If using a sonic container insert, raise the insert above the level of the fluid and drop down to the resting level as the stirring action. Continuously agitate during this step, but do not sonicate. 9.1.43 Pour the solution with the dermis into the sieve over a sink or dump bucket.
• the dermis is to be spread out on the sieve and sprayed front and back with purified water.
• the tissue is to be sprayed as to have saturated all of the tissue with the purified water.
• 14.1.82 Pour the solution with the dermis into the sieve over a sink or dump bucket. 14.1.83 Place each piece of dermis between two pieces of folded sterile absorbent material (e.g., "tex-wipes") and press to dry the tissue as completely as possible. Ensure that the dermis is as flat as possible. 14.1.84 The dermis is to be laid flat in the lyophilization bag and sealed as not to allow the tissue to fall out of the bag. If required, the tissue may be cut prior to placement into a lyophilization bag Try to maintain the tissue in a flat single layer in the lyophilization bag.
• sterile absorbent material e.g., "tex-wipes”
• the process can be stopped after any one of the following steps: Removal of Epidermis with Sodium Chloride, Microbial Reduction with Benzalkonium Chloride, Cell Lysis with Hydrogen Peroxide and Tween, it tne Dermis is rinsed appropriately.
• the process can also be stopped after the step, Rinse (3x) to Remove Buffer.
• the dermis can be doubled bagged, labeled with the donor #, the last step processed and frozen.
• volume of fluids to be used.

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• Health & Medical Sciences (AREA)
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• Biomedical Technology (AREA)
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• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Medicinal Chemistry (AREA)
• Dermatology (AREA)
• Transplantation (AREA)
• Oral & Maxillofacial Surgery (AREA)
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• 2001
  • 2001-09-20 WO PCT/US2001/029572 patent/WO2002024244A2/en not_active Application Discontinuation
  • 2001-09-20 EP EP01973325A patent/EP1333870A2/de not_active Withdrawn
  • 2001-09-20 AU AU2001292917A patent/AU2001292917A1/en not_active Abandoned

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