Functional fabrication of recombinant human collagen-phosphorylcholine hydrogels for regenerative medicine applications
Functional fabrication of recombinant human collagen-phosphorylcholine hydrogels for regenerative medicine applications
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DOI：
10.1016/j.actbio.2014.10.035
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发表时间：
2015-01-15
影响因子：
9.7
通讯作者：
Griffith, May
中科院分区：
文献类型：
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作者：
Islam, M. Mirazul;Cepla, Vytautas;Griffith, May
植入物-宿主界面是引导组织或器官再生的关键因素。我们之前开发了由重组人III型胶原和2-甲基丙烯酰氧乙基磷酰胆碱(RHCIII-MPC)互穿网络组成的水凝胶，作为角膜细胞外基质的替代品，促进角膜组织的内源性再生。为了使它们具有临床应用的功能性，我们现在已经优化了它们的组成，从而提高了它们的机械性能。我们已经证明，这种优化的RHCIII-MPC水凝胶适用于精确的飞秒激光切割，以生产补充植入物和后续组织焊接的手术床。这避免了与手动手术技术相关的组织损伤和炎症，从而导致更有效的愈合。虽然我们之前在临床测试中证明了基于RHCIII的植入物可以刺激患者的角膜再生，但植入物的上皮细胞覆盖率需要改进，例如对植入物表面的修改。我们现在表明，我们的500亩厚的RHCIII-MPC结构包含超过85%的水，适合于纤维连接蛋白的微接触打印。与裸露的RHCIII-MPC水凝胶不同，由此产生的纤维连接蛋白微图案可促进细胞黏附。有趣的是，30微米宽的纤维连接蛋白条带增强了细胞附着，并显示出最高的有丝分裂率，这一效果可能被用于更快地整合植入物。因此，我们已经证明，实验室生产的天然胶原和磷脂的模拟物可以被制造成坚固的水凝胶，可以被激光剖面化和图案化，以增强其作为供体人类角膜的人工替代品的潜在功能。(C)2014年Acta Materialia Inc.，由Elsevier Ltd.出版。
The implant-host interface is a critical element in guiding tissue or organ regeneration. We previously developed hydrogels comprising interpenetrating networks of recombinant human collagen type III and 2-methacryloyloxyethyl phosphorylcholine (RHCIII-MPC) as substitutes for the corneal extracellular matrix that promote endogenous regeneration of corneal tissue. To render them functional for clinical application, we have now optimized their composition and thereby enhanced their mechanical properties. We have demonstrated that such optimized RHCIII-MPC hydrogels are suitable for precision femtosecond laser cutting to produce complementing implants and host surgical beds for subsequent tissue welding. This avoids the tissue damage and inflammation associated with manual surgical techniques, thereby leading to more efficient healing. Although we previously demonstrated in clinical testing that RHCIII-based implants stimulated cornea regeneration in patients, the rate of epithelial cell coverage of the implants needs improvement, e.g. modification of the implant surface. We now show that our 500 mu m thick RHCIII-MPC constructs comprising over 85% water are suitable for microcontact printing with fibronectin. The resulting fibronectin micropatterns promote cell adhesion, unlike the bare RHCIII-MPC hydrogel. Interestingly, a pattern of 30 mu m wide fibronectin stripes enhanced cell attachment and showed the highest mitotic rates, an effect that potentially can be utilized for faster integration of the implant. We have therefore shown that laboratory-produced mimics of naturally occurring collagen and phospholipids can be fabricated into robust hydrogels that can be laser profiled and patterned to enhance their potential function as artificial substitutes of donor human corneas. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd.