Method for processing and preserving collagen-based tissues for transplantation

a collagen-based tissue and tissue technology, applied in the field of collagen-based tissue processing and preservation, can solve the problems of loss of endothelium and smooth muscle cell hypoxia, death, and other complications of transplanted veins, and achieve the effects of reducing procurement damage, enhancing selective preservation, and minimizing surface tension damag

Inactive Publication Date: 2006-09-21
LIFECELL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0016] In its preferred form, the method of this invention includes the steps of processing biological tissues including treatment with a stabilizing solution to reduce procurement damage, treatment with a processing solution to remove cells and other antigenic tissue components, treatment with a cryoprotectant solution, freezing and storage under specific conditions to avoid functionally significa

Problems solved by technology

Despite major advancements in this field, modern tissue transplantation remains associated with complications including inflammation, degradation, scarring, contracture, calcification (hardening), occlusion and rejection.
Unfortunately, however, other complications can ensue with autologous transplants.
For example, significant damage can occur to several tissue components of transplanted veins during harvesting and prior to implantation.
This damage can include mechanical contraction of the smooth muscle cells in the vein wall leading to loss of endothelium and smooth muscle cell hypoxia and death.
Hypoxic damage can result in the release of cellular lysosomes, enzymes which can cause significant damage to the extracellular matrix.
Following implantation, such damage can lead to increased platelet adhesion, leucocyte and macrophage infiltration and subsequently further damage to the vessel wall.
The end result of such damage is thrombosis and occlusion in the early post implant period.
Even in the absence of such damage, transplanted autologous veins typically undergo thickening of the vessel wall and advancing atherosclerosis leading to late occlusion.
Dividing epidermal cells will ultimately grow into and cover the areas of the slits, however, the underlying dermal support matrix does not readily expand into these areas.
Absence of a dermal matrix results in scarring and contracture in the area of the slits.
This contracture can be severe and in cases of massively burned patients that undergo ex

Method used

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  • Method for processing and preserving collagen-based tissues for transplantation
  • Method for processing and preserving collagen-based tissues for transplantation

Examples

Experimental program
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Effect test

example 1

Processing and Storage of Transplantable Skin

[0140] Human donor skin is routinely harvested from cadavers and stored under refrigerated or frozen conditions at a number of tissue banks throughout the nation. This skin is used as a temporary dressing for burn victims that are undergoing extensive autografting. Porcine skin is also harvested under similar conditions and used as a temporary burn dressing. In its unprocessed condition, the allogeneic skin and porcine skin are ultimately rejected by the patient. This same skin is also available for processing by the methods described below.

[0141] Donor skin is harvested under aseptic conditions with a dermatome, and maintained at 4° C. in RPMI 1640 tissue culture media containing penicillin and streptomycin solution for no more than 7 days prior to further processing. Transportation to LifeCell's tissue processing center is via overnight delivery, on wet ice, in the same media. On arrival at the processing center, the temperature of th...

example 2

Vascular Conduit: Human Donor Saphenous Veins

[0163] Saphenous veins are harvested from cadaver donors and made available by tissue banks across the U.S. Tissue banks have established procurement guidelines, published by the American Association of Tissue Banks. These guidelines include instructions for patient selection, completion of consent forms and a caution to avoid mechanical distention or other mechanical damage to the vein during the dissection process.

[0164] Harvesting begins with flushing and distension of the vein with Vein Flushing Solution, consisting of 1000 cc PlasmaLyte Solution for injection, amended with 5000 units of Heparin and 120 mg of Papaverine (1 liter per vein). The veins are carefully removed under sterile conditions with as many tributaries maintained intact as possible, with a length of at least 5 mm. These tributaries are ligated with 3-0 silk. The surrounding fatty tissue is also maintained with wide margins around the vein. Once the vein is removed,...

example 3

Vascular Conduit Processing for Animal Study

Procurement

[0178] Twenty to thirty kilogram mongrel dogs of either sex are induced via sodium pentathol, intubated, and prepped and draped in a sterile fashion. Anaeshesia is maintained with oxygen, nitrogen, and Halothane. A midline incision is made in the neck whereupon the external jugular veins and internal carotid arteries are exposed, isolated, and freed of surrounding fascia. During this procedure, a flushing solution comprised of 5000 units of heparin and 120 mg of Papavarine in 1000 cc sterile Hank's Buffered Saline Solution (HBSS) of pH 7.4 is sprayed on the vessels via a needle and syringe. The proximal and distal ends of the vessel are then clamped with atraumatic vascular clamps whereupon the vessel is rapidly excised. Immediately the vessel is flushed through and through with the above mentioned flushing solution and placed in 4° C. flushing solution for transport. Alternatively, the vessel may be placed in the below menti...

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Abstract

A method for processing and preserving an acellular collagen-based tissue matrix for transplantation is disclosed. The method includes the steps of processing biological tissues with a stabilizing solution to reduce procurement damage, treatment with a processing solution to remove cells, treatment with a cryoprotectant solution followed by freezing, drying, storage and rehydration under conditions that preclude functionally significant damage and reconstitution with viable cells.

Description

RELATED APPLICATION [0001] This application is a continuation-in-part of copending application Ser. No. 835,138 filed Feb. 12, 1992 which is a continuation-in-part of copending application Ser. No. 07 / 709,504 filed Jun. 3, 1991 which is a continuation-in-part of application Ser. No. 07 / 581,584 filed Sep. 12, 1990.BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] This invention relates to methods for procuring decellularizing and further processing and dry preserving collagen-based tissues derived from humans and animals for transplantation into humans or other animals. These methods produce a tissue product that consists of a selectively preserved extracellular protein matrix that is devoid of certain viable cells which normally express major histocompatibility complex antigenic determinants and other antigens which would be recognized as foreign by the recipient. This extracellular protein matrix is made up of collagen and other proteins and provides a structural ...

Claims

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Application Information

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IPC IPC(8): A01N1/02C12N5/08A01N1/00A61K35/18A61K39/13A61L27/36C12N1/04F25C1/14F26B5/06
CPCA01N1/00A01N1/02A01N1/0221A01N1/0231A61K35/18A61K39/13A61L27/3604A61L27/3683A61L27/3808A61L27/3813A61L2430/40C12N1/04C12N2770/32634F25C1/142F26B5/065A61K39/12
Inventor LIVESEY, STEPHEN A.DEL CAMPO, ANTHONY A.NAG, ABHIJITNICHOLS, KEN B.GRIFFEY, EDWARD S.COLEMAN, CHRISTOPHER
Owner LIFECELL
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