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首页> 外文期刊>Acta biomaterialia >Crosslinked collagen hydrogels as corneal implants: effects of sterically bulky vs. non-bulky carbodiimides as crosslinkers.
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Crosslinked collagen hydrogels as corneal implants: effects of sterically bulky vs. non-bulky carbodiimides as crosslinkers.

机译：交联的胶原蛋白水凝胶作为角膜植入物：空间体积大的非碳化碳二亚胺作为交联剂的作用。

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We have previously shown that recombinant human collagen can be crosslinked with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) to fabricate transparent hydrogels possessing the shape and dimensions of the human cornea. These corneal implants have been tested in a Phase I human clinical study. Although these hydrogels successfully promoted corneal tissue and nerve regeneration, the gelling kinetics were difficult to control during the manufacture of the implants. An alternative carbodiimide capable of producing hydrogels of similar characteristics as EDC in terms of strength and biocompatibility, but with a longer gelation time would be a desirable alternative. Here, we compared the crosslinking kinetics and properties of hydrogels crosslinked with a sterically bulky carbodiimide, N-Cyclohexyl-N'-(2-morpholinoethyl) carbodiimide metho-p-toluenesulfonate (CMC), with that of EDC. CMC crosslinking was possible at ambient temperature whereas the EDC reaction was too rapid to control and had to be carried out at low temperatures. The highest tensile strength obtained using optimized formulations were equivalent, although CMC crosslinked hydrogels were found to be stiffer. The collagenase resistance of CMC crosslinked hydrogels was superior to that of EDC crosslinked hydrogels while biocompatibility was similar. We are also able to substitute porcine collagen with recombinant human collagen and show that the in vivo performance of both resulting hydrogels as full-thickness corneal implants is comparable in a mouse model of an orthotopic corneal graft. In conclusion, CMC is a viable alternative to EDC as a crosslinker for collagen-based biomaterials for use as corneal implants, and potentially for use in other tissue engineering applications.
机译：先前我们已经表明，重组人胶原蛋白可以与N-（3-二甲基氨基丙基）-N'-乙基碳二亚胺（EDC）交联，以制备具有人角膜形状和尺寸的透明水凝胶。这些角膜植入物已在I期人类临床研究中进行了测试。尽管这些水凝胶成功地促进了角膜组织和神经再生，但是在植入物的制造过程中难以控制胶凝动力学。在强度和生物相容性方面能够产生与EDC相似特性的水凝胶但具有更长的胶凝时间的替代碳二亚胺将是理想的选择。在这里，我们比较了与空间庞大的碳二亚胺，N-环己基-N'-（2-吗啉代乙基）碳二亚胺，对-对-甲苯磺酸盐（CMC）交联的水凝胶的交联动力学和性质，以及EDC。 CMC交联在环境温度下是可能的，而EDC反应太快而无法控制，必须在低温下进行。尽管发现CMC交联水凝胶更硬，但使用优化配方获得的最高抗拉强度是等效的。 CMC交联水凝胶的胶原酶抗性优于EDC交联水凝胶，而生物相容性相似。我们还能够用重组人胶原蛋白替代猪胶原蛋白，并证明两种所得水凝胶作为全厚度角膜植入物的体内性能在原位角膜移植物的小鼠模型中均具有可比性。总之，CMC是EDC的可行替代品，可作为交联剂用于基于胶原的生物材料，用作角膜植入物，并有可能用于其他组织工程应用。

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