Decellularized corneal lenticule embedded compressed collagen: toward a suturable collagenous construct for limbal reconstruction
Decellularized corneal lenticule embedded compressed collagen: toward a suturable collagenous construct for limbal reconstruction
复制标题
DOI：
10.1088/1758-5090/aad1a4
复制
发表时间：
2018-10-01
期刊：
影响因子：
9
通讯作者：
Kim, Dong Sung
中科院分区：
文献类型：
--
作者：
Hong, Hyeonjun;Huh, Man-Il;Kim, Dong Sung
近年来，压缩胶原蛋白作为一种潜在的替代角膜缘上皮干细胞（LESC）载体治疗角膜缘干细胞缺乏症（LSCD）备受关注，因为与传统的胶原水凝胶相比，压缩胶原蛋白可以提供机械改良的胶原纤维结构。然而，由于其机械强度有限，无法承受手术缝合所产生的力，且对酶降解的抵抗力较低，其作为LESC载体的临床疗效尚未通过体内移植进行研究。本研究首次提出了一种可缝合的LESC载体，该载体以生物复合材料的形式基于压缩胶原。这种生物复合材料是通过将脱细胞角膜小颗粒（一种从角膜屈光手术中获得的脱细胞间质组织）整合到压缩的胶原蛋白中形成三明治结构来实现的。缝合保持测试证实，与压缩胶原蛋白（0.02 +/- 0.01 N）相比，生物复合材料具有更高的缝合保持强度（0.56 +/- 0.12 N）。该生物复合材料还表现出3倍以上的酶降解抗性，表明移植后的长期稳定性。体外细胞培养结果表明，该生物复合材料有效地支持了LESCs的扩增和分层，并表达了推测的干细胞和分化的角膜上皮细胞标记物。最后，通过稳定地将LESCs植入LSCD兔眼模型，有效地重建眼表，验证了该生物复合材料的临床疗效。
Recently, compressed collagen has attracted much attention as a potential alternative for a limbal epithelial stem cell (LESC) carrier to treat limbal stem cell deficiency (LSCD), in that it can provide mechanically improved collagen fibrillar structures compared to conventional collagen hydrogel. However, its clinical efficacy as an LESC carrier has not yet been studied through in vivo transplantation due to limited mechanical strength that cannot withstand a force induced by surgical suturing and low resistance to enzymatic degradation. This study firstly presents a suturable LESC carrier based on compressed collagen in the form of a biocomposite. The biocomposite was achieved by integrating a decellularized corneal lenticule, which is a decellularized stromal tissue obtained from corneal refractive surgery, inside a compressed collagen to form a sandwich structure. Asuture retention test verified that the biocomposite has a much higher suture retention strength (0.56 +/- 0.12 N) compared to the compressed collagen (0.02 +/- 0.01 N). The biocomposite also exhibited more than 3 times higher resistance to enzymatic degradation, indicating long-term stability after transplantation. In vitro cell culture results revealed that the biocomposite effectively supported the expansion and stratification of the LESCs with expressions of putative stem cell and differentiated corneal epithelial cell markers. Finally, the biocomposite verified its clinical efficacy by stably delivering the LESCs onto an eye of a rabbit model of LSCD and effectively reconstructing the ocular surface.