Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, United States; Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, United States.
Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, United States.
Mater Sci Eng C Mater Biol Appl. 2021 May;124:112075. doi: 10.1016/j.msec.2021.112075. Epub 2021 Mar 24.
Most of the synthetic polymer-based hydrogels lack the intrinsic properties needed for tissue engineering applications. Here, we describe a biomimetic approach to induce the mineralization and vascularization of poly(ethylene glycol) (PEG)-based hydrogel to template the osteogenic activities. The strategy involves the covalent functionalization of oligo[poly(ethylene glycol) fumarate] (OPF) with phosphate groups and subsequent treatment of phosphorylated-OPF (Pi-OPF) hydrogels with alkaline phosphatase enzyme (ALP) and calcium. Unlike previously reported studies for ALP induced mineralization, in this study, the base polymer itself was modified with the phosphate groups for uniform mineralization of hydrogels. In addition to improvement of mechanical properties, enhancement of MC3T3-E1 cell attachment and proliferation, and promotion of mesenchymal stem cells (MSC) differentiation were observed as the intrinsic benefits of such mineralization. Current bone tissue engineering (BTE) research endeavors are also extensively focused on vascular tissue regeneration due to its inherent advantages in bone regeneration. Taking this into account, we further functionalized the mineralized hydrogels with FG-4592, small hypoxia mimicking molecule. The functionalized hydrogels elicited upregulated in vitro angiogenic activities of human umbilical vein endothelial cells (HUVEC). In addition, when implanted subcutaneously in rats, enhanced early vascularization activities around the implantation site were observed as demonstrated by the immunohistochemistry results. This further leveraged the formation of calcified tissues at the implantation site at later time points evident through X-ray imaging. The overall results here show the perspectives of bifunctional OPF hydrogels for vascularized BTE.
大多数基于合成聚合物的水凝胶缺乏组织工程应用所需的固有特性。在这里，我们描述了一种仿生方法，可诱导聚（乙二醇）（PEG）基水凝胶的矿化和血管化，以模板化成骨活性。该策略涉及将寡聚[聚（乙二醇）富马酸]（OPF）与磷酸基团共价功能化，然后用碱性磷酸酶（ALP）和钙处理磷酸化-OPF（Pi-OPF）水凝胶。与以前报道的用于 ALP 诱导矿化的研究不同，在这项研究中，基聚合物本身用磷酸基团进行了修饰，以实现水凝胶的均匀矿化。除了改善机械性能外，还观察到 MC3T3-E1 细胞附着和增殖的增强，以及间充质干细胞（MSC）分化的促进，这是这种矿化的内在益处。由于其在骨再生中的固有优势，当前的骨组织工程（BTE）研究也广泛集中在血管组织再生上。考虑到这一点，我们进一步用 FG-4592（一种小的缺氧模拟分子）对矿化水凝胶进行了功能化。功能化的水凝胶引起了人脐静脉内皮细胞（HUVEC）体外血管生成活性的上调。此外，当皮下植入大鼠时，通过免疫组织化学结果观察到植入部位周围早期血管化活性增强。这进一步利用了 X 射线成像显示的在稍后时间点在植入部位形成钙化组织的能力。总体结果表明，双功能 OPF 水凝胶在血管化 BTE 方面具有前景。
