Engineering a macroporous fibrin-based sequential interpenetrating polymer network for dermal tissue engineering
Engineering a macroporous fibrin-based sequential interpenetrating polymer network for dermal tissue engineering
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真皮组织工程大孔纤维蛋白序贯互穿聚合物网络
DOI：
10.1039/d0bm01161d
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发表时间：
2020-12-21
影响因子：
6.6
通讯作者：
Bencherif, Sidi A.
中科院分区：
文献类型：
--
作者：
Gsib, Olfat;Eggermont, Loek J.;Bencherif, Sidi A.
用于深层伤口愈合的皮肤组织工程的成功主要依赖于创新和有效的生物材料的设计。这项研究报告了一种用于皮肤修复的新型天然大孔互穿聚合物网络（IPN）的合成和表征。这些生物材料由生物活性纤维蛋白网络组成，该网络聚合在由聚乙二醇和可生物降解的血清白蛋白（PEGDM-co-SAM）制成的机械坚固的大孔结构内。首先，合成介孔 PEGDM-co-SAM 水凝胶并进行冷冻处理以引入互连的大孔网络。随后，纤维蛋白前体被纳入冷冻处理的基于 PEG 的网络中，然后自发聚合并形成连续的 IPN。流变学测量表明，与单独的纤维蛋白水凝胶相比，基于纤维蛋白的顺序 IPN 水凝胶表现出改进且可调节的机械性能。体外数据表明，人真皮成纤维细胞在 IPN 构建体中粘附、渗透和增殖，并且能够分泌内源性细胞外基质蛋白，即胶原蛋白 I 和纤连蛋白。此外，一项针对小鼠的临床前研究表明，IPN 在皮下植入后 1 个月内保持稳定，诱导最小的宿主炎症反应，并在结构内显示出大量的细胞浸润和组织重塑。总的来说，这些数据表明，大孔和机械增强的基于纤维蛋白的序列 IPN 水凝胶是有前途的真皮组织再生三维平台。
The success of skin tissue engineering for deep wound healing relies predominantly on the design of innovative and effective biomaterials. This study reports the synthesis and characterization of a new type of naturally-derived and macroporous interpenetrating polymer network (IPN) for skin repair. These biomaterials consist of a biologically active fibrous fibrin network polymerized within a mechanically robust and macroporous construct made of polyethylene glycol and biodegradable serum albumin (PEGDM-co-SAM). First, mesoporous PEGDM-co-SAM hydrogels were synthesized and subjected to cryotreatment to introduce an interconnected macroporous network. Subsequently, fibrin precursors were incorporated within the cryotreated PEG-based network and then allowed to spontaneously polymerize and form a sequential IPN. Rheological measurements indicated that fibrin-based sequential IPN hydrogels exhibited improved and tunable mechanical properties when compared to fibrin hydrogels alone. In vitro data showed that human dermal fibroblasts adhere, infiltrate and proliferate within the IPN constructs, and were able to secrete endogenous extracellular matrix proteins, namely collagen I and fibronectin. Furthermore, a preclinical study in mice demonstrated that IPNs were stable over 1-month following subcutaneous implantation, induced a minimal host inflammatory response, and displayed a substantial cellular infiltration and tissue remodeling within the constructs. Collectively, these data suggest that macroporous and mechanically reinforced fibrin-based sequential IPN hydrogels are promising three-dimensional platforms for dermal tissue regeneration.