CHEMICALLY MODIFIED COLLAGEN - A NATURAL BIOMATERIAL FOR TISSUE REPLACEMENT
CHEMICALLY MODIFIED COLLAGEN - A NATURAL BIOMATERIAL FOR TISSUE REPLACEMENT
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DOI：
10.1002/jbm.820210606
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发表时间：
1987-06-01
期刊：
影响因子：
--
通讯作者：
SHEIKH, K
中科院分区：
文献类型：
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作者：
NIMNI, ME;CHEUNG, D;SHEIKH, K
天然或重组胶原纤维和富含胶原蛋白的组织的戊二醛交联会显著降低生物降解率。其他醛在产生化学、生物和热稳定的交联物方面不如戊二醛有效。用戊二醛交联的组织保留了天然胶原纤维网络的许多粘弹性特性，这使得它们适合于生物假体。以戊二醛为交联剂的胶原材料植入物长期会发生钙化、生物降解和低度免疫反应。我们试图通过(A)活化的羧基与二胺的桥联和(B)使用戊二醛使胶原中的β-NH2基团和脂族二胺引入的未反应的胺进行交联来克服这些问题。这种交联减少了组织的降解，几乎消除了体液抗体的诱导。二膦酸盐，特别是3-氨基-1-羟基丙烷-1，1-二膦酸(3-apd)和硫酸软骨素与胶原或交联增强的胶原网络的共价结合降低了其钙化的可能性。戊二醛交联会减少血小板聚集，而硫酸软骨素与胶原的共价结合几乎可以消除血小板聚集。细胞毒性和残留的戊二醛--通过胶原纤维或组织基质的间隙渗出--以及与结合的聚合物戊二醛相关的反应性醛，可以通过中和和彻底漂洗，在无毒的抑菌溶液中储存后降低。
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 (a) bridging of activated carboxyl groups with diamines and (b) 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 and 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.