Munoz-Pinto Dany J, Jimenez-Vergara Andrea Carolina, Gharat Tanmay P, Hahn Mariah S
Department of Biomedical Engineering, Rensselaer Polytechnic Institute, 110 8th Street Troy, NY, 12180, USA.
Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, 110 8th Street Troy, NY, 12180, USA.
Biomaterials. 2015 Feb;40:32-42. doi: 10.1016/j.biomaterials.2014.10.051. Epub 2014 Nov 27.
Collagen hydrogels have been widely investigated as scaffolds for vascular tissue engineering due in part to the capacity of collagen to promote robust cell adhesion and elongation. However, collagen hydrogels display relatively low stiffness and strength, are thrombogenic, and are highly susceptible to cell-mediated contraction. In the current work, we develop and characterize a sequentially-formed interpenetrating network (IPN) that retains the benefits of collagen, but which displays enhanced mechanical stiffness and strength, improved thromboresistance, high physical stability and resistance to contraction. In this strategy, we first form a collagen hydrogel, infuse this hydrogel with poly(ethylene glycol) diacrylate (PEGDA), and subsequently crosslink the PEGDA by exposure to longwave UV light. These collagen-PEGDA IPNs allow for cell encapsulation during the fabrication process with greater than 90% cell viability via inclusion of cells within the collagen hydrogel precursor solution. Furthermore, the degree of cell spreading within the IPNs can be tuned from rounded to fully elongated by varying the time delay between the formation of the cell-laden collagen hydrogel and the formation of the PEGDA network. We also demonstrate that these collagen-PEGDA IPNs are able to support the initial stages of smooth muscle cell lineage progression by elongated human mesenchymal stems cells.
胶原水凝胶作为血管组织工程的支架已被广泛研究，部分原因是胶原具有促进强大细胞黏附和伸长的能力。然而，胶原水凝胶表现出相对较低的硬度和强度，具有血栓形成性，并且极易受到细胞介导的收缩影响。在当前工作中，我们开发并表征了一种顺序形成的互穿网络（IPN），它保留了胶原的优点，但具有增强的机械硬度和强度、改善的抗血栓性、高物理稳定性和抗收缩性。在该策略中，我们首先形成胶原水凝胶，用聚（乙二醇）二丙烯酸酯（PEGDA）灌注该水凝胶，随后通过暴露于长波紫外光使PEGDA交联。这些胶原 - PEGDA IPN在制造过程中允许细胞包封，通过将细胞包含在胶原水凝胶前体溶液中，细胞活力大于90%。此外，通过改变载有细胞的胶原水凝胶形成与PEGDA网络形成之间的时间延迟，IPN内细胞铺展的程度可以从圆形调整为完全伸长。我们还证明，这些胶原 - PEGDA IPN能够支持伸长的人间充质干细胞向平滑肌细胞谱系进展的初始阶段。
