Chemically modified collagen: A natural biomaterial for tissue replacement

Abstract

Glutaraldehyde crosslinking of native or reconstituted collagen fibrils and tissues rich in collagen significantly reduces biodegradation. Other aldehydes are less efficient than glutaraldehyde in generating chemically, biologically, and thermally stable crosslinks. Tissues crosslinked with glutaraldehyde retain many of the viscoelastic properties of the native collagen fibrillar network which render them suitable for bioprostheses. Implants of collagenous materials crosslinked with glutaraldehyde are subject long-term to calcification, biodegradation, and low-grade immune reactions. We have attempted to overcome these problems by enhancing crosslinking through bridging of activated carboxyl groups with diamines and using glutaraldehyde to crosslink the epsilon-NH2 groups in collagen and the unreacted amines introduced by aliphatic diamines. This crosslinking reduces tissue degradation and nearly eliminates humoral antibody induction. Covalent binding of diphosphonates, specifically 3-amino-1-hydroxypropane-1, 1-diphosphonic acid (3-APD), and chondroitin sulfate to collagen or to the crosslink-enhanced collagen network reduces its potential for calcification. Platelet aggregation is also reduced by glutaraldehyde crosslinking and nearly eliminated by the covalent binding of chondroitin sulfate to collagen. The cytotoxicity of residual glutaraldehyde--leaching through the interstices of the collagen fibrils or the tissue matrix--and of reactive aldehydes associated with the bound polymeric glutaraldehyde can be minimized by neutralization and thorough rinsing after crosslinking and storage in a nontoxic bacteriostatic solution.

Silk based biomaterials to heal critical sized femur defects

“…Ceramics generally have very low tensile strength, are brittle, and cannot be used in locations of significant torsion such as long bones [3,4,[59][60][61]. Alternatively, biomaterials such as type I collagen base implants are frequently used but have limitations related to rapid biodegradation or -when stabilized through cross-linking -foreign body responses and uncontrolled calcification [62,63].…”

Collagen scaffolds for tissue engineering

“…4 Concerns have been raised about cytotoxicity 5,6 and bioincompatibility 7 of some glutaraldehyde crosslinked collagens. Cytotoxicity can be minimized by neutralization, 8 by using lower concentrations of glutaraldehyde, 9 or by substitution with other tanning agents, such as…”

Transdentinal Cytotoxicity of Carbodiimide (EDC) and Glutaraldehyde on Odontoblast-like Cells

“…EDC is capable of forming covalent peptide bonds between peptide chains by activating the free carboxyl group of glutamic and aspartic acids, 21,22 while GA reacts with the e-amino groups of lysyl or hydroxylysyl residues to induce the formation of intra-and intermolecular cross-links. 23,24 Although the effects of EDC and GA have been demonstrated on collagen biomodification, 18,25 rendering collagen more resistant to degradation by improving its mechanical properties, such as elastic modulus and ultimate tensile strength, and MMP inhibiton, 19,20 there is little information available about their cytotoxicity. The carbodiimides have shown better results than has GA in terms of the biocompatibility on U937 macrophage-like cells, 26 rat ocular cells/tissue, 27 and corneal endothelial cells.…”