UCL Institute of Orthopaedics and Musculoskeletal Sciences, UCL Tissue Repair and Engineering Centre, University College London, Stanmore Campus, London HA7 4LP, UK.
UCL Institute of Orthopaedics and Musculoskeletal Sciences, UCL Tissue Repair and Engineering Centre, University College London, Stanmore Campus, London HA7 4LP, UK; Institute of Biophysics and Biomedical Engineering, Faculty of Sciences of the University of Lisbon, Lisbon, Portugal.
Acta Biomater. 2014 Dec;10(12):5005-5011. doi: 10.1016/j.actbio.2014.08.038. Epub 2014 Sep 6.
Currently one factor hindering the development of collagen hydrogel constructs for tissue engineering is the mismatch between initial cellularity and mechanical strength. The main advantage of collagen hydrogel tissue constructs is their ability to support interstitially seeded cells. However, cells are sensitive to their environment, in particular, substrate stiffness, which cannot easily be replicated within hydrogels without cytotoxic cross-linking treatment. In this study, pre-crosslinked polymeric collagen fibrils are introduced as a starting material, thereby avoiding artificial cross-linking. Shear aggregation of this material in solution results in fibril alignment, but cell addition is only possible when polymeric collagen is blended with its monomeric counterparts to slow the aggregation of collagen fibrils. The hydrogel can then be brought to physiological collagen density by plastic compression. Interstitially seeded fibroblasts were supported for 14days. Although compression of blended gels resulted in some cell death due to increased rate of fluid expulsion, not normally seen in conventional collagen hydrogels, the surviving cell population recovers during subsequent culture. Importantly, the compression process can be controlled and customized to limit cell damage. This is the first report of native polymeric collagen used in a tissue engineering context, for the rapid production of a stiff collagen-cell constructs.
目前，阻碍胶原蛋白水凝胶构建物在组织工程中发展的一个因素是初始细胞密度和机械强度之间的不匹配。胶原蛋白水凝胶组织构建物的主要优势在于其能够支持间质接种细胞。然而，细胞对其环境很敏感，特别是基质硬度，在没有细胞毒性交联处理的情况下，水凝胶中很难轻易复制。在这项研究中，引入了预交联的聚合物胶原原纤维作为起始材料，从而避免了人工交联。该材料在溶液中的剪切聚集导致纤维排列，但只有在聚合物胶原与单体胶原混合以减缓胶原纤维聚集时，才能添加细胞。然后可以通过塑性压缩将水凝胶带到生理胶原蛋白密度。间质接种的成纤维细胞在 14 天内得到支持。尽管由于流体排出率增加，混合凝胶的压缩导致一些细胞死亡，这在常规胶原蛋白水凝胶中通常不会发生，但在随后的培养过程中，存活的细胞群会恢复。重要的是，压缩过程可以控制和定制，以限制细胞损伤。这是首次在组织工程背景下使用天然聚合物胶原快速生产硬胶原蛋白细胞构建物的报告。
