Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Nam-gu, Pohang, Gyeongbuk, 37673, Republic of Korea.
Department of Ophthalmology, School of Medicine, Kyungpook National University, Jung-gu, Daegu, 41944, Republic of Korea.
Biofabrication. 2020 Oct 1;12(4):045030. doi: 10.1088/1758-5090/abb52a.
Despite the potential of a collagen construct, consisting of a major extracellular matrix component of the native cornea, as a patch graft to treat the corneal perforation, there has still been difficulty in acquiring sufficient mechanical properties for clinical availability. This study developed a novel in situ photochemical crosslinking (IPC)-assisted collagen compression process, namely, the IPC-C process, to significantly enhance the mechanical properties of the collagen construct for the development of a collagenous patch graft. For the first time, we found that compressed collagen construct was rapidly rehydrated in an aqueous solution, which inhibited effective riboflavin-mediated photochemical crosslinking for mechanical improvement. The IPC-C process was designed to concurrently induce the physical compaction and photochemical crosslinking of a compressed collagen construct, thereby avoiding the loosening of collagen fibrillar structure during rehydration and ultimately improving crosslinking efficiency. Hence, the suggested IPC-C process could fabricate a collagen construct with a high collagen density (∼120-280 mg ml) and ∼10-fold increased mechanical properties (an elastic modulus of up to ∼29 MPa and ultimate tensile strength of ∼8 MPa) compared with collagen gel. This construct can then be used as a clinically applicable collagenous patch graft. With sufficient mechanical strength for surgical suture and the controllable thickness for patient specificity, the potential of the fabricated IPC-compressed collagen construct for clinical applications was demonstrated by using an in vivo rabbit corneal perforation model. It effectively protected aqueous humor leakage and maintained the integrity of the eye globe without an additional complication.
尽管由天然角膜的主要细胞外基质成分组成的胶原构建体作为一种贴片移植物治疗角膜穿孔具有潜力，但仍然难以获得足够的机械性能以达到临床应用的要求。本研究开发了一种新颖的原位光化学交联（IPC）辅助胶原压缩工艺，即 IPC-C 工艺，以显著提高胶原构建体的机械性能，从而开发胶原贴片移植物。我们首次发现，压缩胶原构建体在水溶液中迅速再水合，这抑制了有效的核黄素介导的光化学交联以提高机械性能。IPC-C 工艺旨在同时诱导压缩胶原构建体的物理压实和光化学交联，从而避免胶原纤维结构在再水合过程中的松动，并最终提高交联效率。因此，所提出的 IPC-C 工艺可以制造出具有高胶原密度（约 120-280mg/ml）和约 10 倍机械性能提高的胶原构建体（弹性模量高达约 29MPa，最大拉伸强度约 8MPa），与胶原凝胶相比。这种构建体可以用作临床应用的胶原贴片移植物。该构建体具有足够的手术缝合强度和可控制的厚度以适应患者的特异性，通过体内兔角膜穿孔模型证明了所制备的 IPC 压缩胶原构建体的临床应用潜力。它有效地防止了房水漏出，并保持了眼球的完整性，没有出现额外的并发症。
