Acellular vascular tissues: natural biomaterials for tissue repair and tissue engineering

doi:10.1016/S0142-9612(00)00148-4

Biomaterials

Volume 21, Issue 22, 15 November 2000, Pages 2215-2231

https://doi.org/10.1016/S0142-9612(00)00148-4 Get rights and content

Abstract

Various research groups around the world are actively investigating cardiovascular prostheses of biological origin. This review article discusses the need for such bioprosthetics and the potential role for natural tissues in cardiovascular applications such as cardiac valves and vascular grafts. Upon implantation, unmodified natural materials are subject to chemical and enzymatic degradation, seriously decreasing the life of the prosthesis. Therefore, methods such as glutaraldehyde and polyepoxide crosslinking treatments and dye-mediated photooxidation have been developed to stabilize the tissue while attempting to maintain its natural mechanical properties. Also, residual cellular components in a bioprosthetic material have been associated with undesired effects, such as calcification and immunological recognition, and thus have been the motivation for various decellularization processes. The effects of these stabilization and decellularization treatments on mechanical, biological and chemical properties of treated tissues have been investigated, specifically with regard to calcification, immunogenicity, and cytotoxicity concerns. Despite significant advances in the area of cardiovascular prostheses, there has yet to be developed a completely biocompatible, long-lasting implant. However, with the recent advent of tissue engineering, the possibility of applying selective cell seeding to naturally derived bioprosthetics moves us closer to a living tissue replacement.

Section snippets

The need for cardiovascular bioprosthetics

For more than 40 years, materials to replace malfunctioning or diseased cardiovascular tissues have been under investigation. Artificial prostheses were introduced into cardiovascular surgery in 1952 when Hufnagel implanted the first artificial heart valve, and in the same year, Voorhees introduced the first artificial vascular graft. Subsequent reconstructive procedures have been developed with the intent of increasing implant biocompatibility, including the transfer of healthy tissue from one

The potential role of natural tissues as cardiovascular biomaterials

The use of xenograft and allograft tissue as part of bioprosthetic vascular devices such as heart valves and vascular grafts has long been the focus of research [14]. The use of these natural biomaterials has typically required chemical or physical pretreatment aimed at (1) preserving the tissue by enhancing the resistance of the material to enzymatic or chemical degradation, (2) reducing the immunogenicity of the material, and (3) sterilizing the tissue. Multiple crosslinking techniques have

Glutaraldehyde treatment: early efforts in preservation of natural tissues

The most commonly accepted crosslinking reagent is glutaraldehyde, a five-carbon bifunctional aldehyde, whose use has dominated since its introduction into biomedicine in the late 1960s [15]. Glutaraldehyde reacts with the ε-amino group of lysyl residues in proteins (e.g., collagen), which induces formation of interchain crosslinks [16] and stabilizes tissues against chemical and enzymatic degradation depending on the extent of crosslinking [17], [18]. Unfortunately, the exact mechanism by

Alternative procedures for preserving tissues

There is considerable interest in identifying and investigating alternative tissue treatments that preserve natural tissue but do not result in the deleterious side effects typically associated with glutaraldehyde treatment. Several of these alternative crosslinking and fixation approaches include the use of carbodiimides such as cyanimide [44], [87], [88] and 1-ethyl-3(-3 dimethyl aminopropyl) carbodiimide hydrochloride (EDC) [89], [90], adipyl dichloride [91], [92], [93], hexamethylene

Extraction of cellular components from natural tissues

In addition to alternative treatments that preserve (i.e., crosslink) natural tissue, methods are being explored to produce completely acellular tissue matrices by specifically removing cellular components that are believed to promote calcification and to give rise to a residual immunological response. These decellularization techniques include chemical, enzymatic and mechanical means of removing cellular components, leaving a material composed essentially of extracellular matrix components.

Tissue engineering prospects for natural biomaterials

The field of tissue engineering has evolved rapidly over the last decade, and many parallel research efforts are underway to create a vast array of living tissue replacements for therapeutic applications [178], [179]. Most of these approaches involve the use of synthetic polymer scaffolds that serve to guide cell growth and tissue morphogenesis [180], [181], [182]. Although various biodegradable synthetic polymers show great promise, there is reason to believe that naturally derived materials

Summary

Many attempts have been made to produce long-lasting, biocompatible cardiovascular implants. To overcome the mechanical and biological limitations of synthetic implants, various researchers have begun to focus on the development of a naturally derived biomaterial for the fabrication of heart valve replacements and vascular grafts. In order for materials to be transplanted to a patient from a donor, especially an animal donor, the tissue must be modified to increase resistance to degradation and

Notes

For an excellent and comprehensive review written on tissue heart valves, refer to Schoen and Levy [4], and for an earlier general review on the use of tissue-derived biomaterials for cardiovascular prosthetics, refer to Hilbert et al. [14].

Acknowledgments

We would like to thank Diane Hern-Anderson, Larry Boerboom, Steve Badylak, and Beth Furnish for technical feedback on the manuscript, and Pam Cook for editorial assistance. We would also like to thank Frederick Schoen, Diane Hern-Anderson, Larry Boerboom, and Steve Badylak for contributions of photos for this review article.

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Acellular vascular tissues: natural biomaterials for tissue repair and tissue engineering

Abstract

Section snippets

The need for cardiovascular bioprosthetics

The potential role of natural tissues as cardiovascular biomaterials

Glutaraldehyde treatment: early efforts in preservation of natural tissues

Alternative procedures for preserving tissues

Extraction of cellular components from natural tissues

Tissue engineering prospects for natural biomaterials

Summary

Notes

Acknowledgments

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Chest

Ann Thorac Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Biomech

Ann Thorac Surg

Ann Thorac Surg

Biomaterials

Biomaterials

J Biomech

J Thorac Cardiovasc Surg

Biomaterials

Ann Thorac Surg

Biomaterials

J Thorac Cardiovasc Surg

Am J Cardiol

Biomaterials

Biomaterials

Biomaterials

J Biomed Mater Res

J Vasc Surg

Cardiovasc Surg

Biomaterials

Biomaterials

Allograft valves for aortic and mitral valve replacement

Curr Opin Cardiol

Tissue heart valvescurrent challenges and future research perspectives

J Biomed Mater Res

Cryopreservation of veins as an alternative to autografts in coronary by-pass grafting

J Cardiovasc Surg (Torino)

Small caliber vascular grafts. Part I. State of the art

J Biomater Appl

The role of glutaraldehyde-induced cross-links in calcification of bovine pericardium used in cardiac valve bioprostheses

Am J Pathol

Chemically modified collagena natural biomaterial for tissue replacement

J Biomed Mater Res

Glutaraldehyde detoxification of aortic wall tissuea promising perspective for emerging bioprosthetic valve concepts

J Heart Valve Dis

Reduction of calcification by various treatments in cardiac valves

Biomater Appl

The inactivation of viruses by germicides

Chem Spec Manuf Proc

Immunological reactivity to a new glutaraldehyde tanned bovine pericardial heart valve

Trans Am Soc Artif Intern Organs

Immunological involvement in porcine bioprosthetic valve degenerationpreliminary studies

Henry Ford Hosp Med J

Extracellular matrix proteinsbystanders or active participants in the allograft rejection cascade?

Ann Transplant

Glutaraldehyde fixation alters the internal shear properties of porcine aortic heart valve tissue

Ann Thorac Surg

The bovine pericardial xenograftI. Effect of fixation in aldehydes without constraint on the tensile viscoelastic properties of bovine pericardium

J Biomed Mater Res

Influence of fixation conditions on the performance of glutaraldehyde-treated porcine aortic valvestowards a more scientific basis

Thorax