Nafea Eman H, Poole-Warren Laura A, Martens Penny J
Graduate School of Biomedical Engineering, UNSW Australia, Sydney, New South Wales, 2052, Australia.
J Biomed Mater Res A. 2015 Dec;103(12):3727-35. doi: 10.1002/jbm.a.35510. Epub 2015 Jun 4.
The presentation of multiple biological cues, which simulate the natural in vivo cell environment within artificial implants, has recently been identified as crucial for achieving complex cellular functions. The incorporation of two or more biological cues within a largely synthetic network can provide a simplified model of multifunctional ECM presentation to encapsulated cells. Therefore, the aim of this study was to examine the effects of simultaneously and covalently incorporating two dissimilar biological molecules, heparin and gelatin, within a PVA hydrogel. PVA was functionalized with 7 and 20 methacrylate functional groups per chain (FG/c) to tailor the permselectivity of UV photopolymerized hydrogels. Both heparin and gelatin were covalently incorporated into PVA at an equal ratio resulting in a final PVA:heparin:gelatin composition of 19:0.5:0.5. The combination of both heparin and gelatin within a PVA network has proven to be stable over time without compromising the PVA base characteristics including its permselectivity to different proteins. Most importantly, this combination of ECM analogues supplemented PVA with the dual functionalities of promoting cellular adhesion and sequestering growth factors essential for cellular proliferation. Multi-functional PVA hydrogels with synthetically controlled network characteristics and permselectivity show potential in various biomedical applications including artificial cell implants.
在人工植入物中呈现多种生物线索以模拟天然的体内细胞环境,最近已被确定为实现复杂细胞功能的关键。在一个主要为合成的网络中纳入两种或更多种生物线索,可以为被封装的细胞提供一个多功能细胞外基质呈现的简化模型。因此,本研究的目的是考察在聚乙烯醇(PVA)水凝胶中同时共价结合两种不同的生物分子——肝素和明胶——的效果。每条链用7个和20个甲基丙烯酸酯官能团(FG/c)对PVA进行功能化,以调整紫外光聚合水凝胶的渗透选择性。肝素和明胶以相等比例共价结合到PVA中,最终得到的PVA:肝素:明胶组成为19:0.5:0.5。已证明,在PVA网络中同时存在肝素和明胶是稳定的,且不会损害PVA的基本特性,包括其对不同蛋白质的渗透选择性。最重要的是,这种细胞外基质类似物的组合为PVA补充了促进细胞黏附以及螯合细胞增殖所必需的生长因子的双重功能。具有合成控制的网络特性和渗透选择性的多功能PVA水凝胶在包括人工细胞植入物在内的各种生物医学应用中显示出潜力。