van Wachem P B, van Luyn M J, Olde Damink L H, Dijkstra P J, Feijen J, Nieuwenhuis P
Department of Histology and Cell Biology, University of Groningen, The Netherlands.
J Biomed Mater Res. 1994 Mar;28(3):353-63. doi: 10.1002/jbm.820280310.
The biocompatibility and tissue regenerating capacity of four crosslinked dermal sheep collagens (DSC) was studied. In vitro, the four DSC versions were found to be noncytotoxic or very low in cytotoxicity. After subcutaneous implantation in rats, hexamethylenediisocyanate-crosslinked DSC (HDSC) seldom induced an increased infiltration of neutrophils or macrophages, as compared with normal wound healing; whereas new formation of collagen was observed. DSC crosslinked with glutaraldehyde (GDSC) followed by reaction with NaBH4 shortly after implantation showed an increased infiltration of neutrophils with a deviant morphology. Furthermore, a high incidence of calcification was observed, which may explain the minor ingrowth of giant cells and fibroblasts, and the poor formation of new rat collagen. Acyl azide-crosslinked DSC (AaDSC) first induced an increased infiltration of macrophages, and then of giant cells, both with high lipid formation. AaDSC degraded at least twice as slowly as HDSC and GDSC, finally leaving a matrix of newly formed rat collagen. Samples crosslinked with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide (ENDSC) induced the same mild cellular reaction as HDSC; whereas, similar to AaDSC, the degradation rate was slow and an optimal rat collagen matrix was formed. Of the crosslinked DSC samples, ENDSC seems most promising for tissue regeneration.
研究了四种交联的绵羊真皮胶原蛋白（DSC）的生物相容性和组织再生能力。在体外，发现这四种DSC版本无细胞毒性或细胞毒性非常低。在大鼠皮下植入后，与正常伤口愈合相比，六亚甲基二异氰酸酯交联的DSC（HDSC）很少引起中性粒细胞或巨噬细胞浸润增加；然而，观察到有新的胶原蛋白形成。植入后不久用戊二醛交联的DSC（GDSC）再与硼氢化钠反应，显示中性粒细胞浸润增加且形态异常。此外，观察到高钙化发生率，这可能解释了巨细胞和成纤维细胞向内生长较少以及新的大鼠胶原蛋白形成较差的原因。酰基叠氮交联的DSC（AaDSC）首先引起巨噬细胞浸润增加，然后是巨细胞浸润增加，两者都有大量脂质形成。AaDSC的降解速度至少比HDSC和GDSC慢两倍，最终留下新形成的大鼠胶原蛋白基质。用1-乙基-3-（3-二甲基氨基丙基）碳二亚胺盐酸盐和N-羟基琥珀酰亚胺交联的样品（ENDSC）引起与HDSC相同的轻度细胞反应；然而，与AaDSC类似，其降解速度较慢并形成了最佳的大鼠胶原蛋白基质。在交联的DSC样品中，ENDSC似乎最有希望用于组织再生。
