School of Biological Science and Medical Engineering, Beihang University, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing, 100083, China; Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, 102402, China.
Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA; Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
Biomaterials. 2019 Dec;223:119458. doi: 10.1016/j.biomaterials.2019.119458. Epub 2019 Aug 29.
Injectable hydrogels are advantageous as tissue regeneration scaffolds, as they can be delivered through a minimally invasive injection and seamlessly integrate with the target tissues. However, an important shortcoming of current injectable hydrogels is the lack of simultaneous control over their micro- and nanoscale structures. In this article, the authors report a strategy for developing injectable hydrogels that integrate a fibrous nanostructure and porous microstructure. The hydrogels are prepared by using novel nanofibrous microparticles as the building blocks. The protein based nanofibrous microparticles, fabricated by a spray freezing technology, can be injected through a syringe-needle system. A cell-compatible photocuring process can be deployed to connect the microparticles and form a mechanically robust hydrogel scaffold. The inter-particle voids combined to form the interconnected micropores and the diameter of the nanofibers (100-300 nm) closely mimics that of the native extracellular matrix. Compared to the non-porous hydrogels and non-fibrous hydrogels, the microparticle annealed nanofibrous (MANF) hydrogels potently enhance the osteogenic-marker expression (ALP, Runx2, OCT and BSP) and mineralization of human mesenchymal stem cells in vitro. MANF hydrogels also facilitate cell infiltration and enhance neovasculization in a subcutaneous implantation model in vivo. The capacity of MANF hydrogels to promote bone regeneration is investigated in a calvarial bone repair model. MANF hydrogels demonstrate significant higher bone regeneration after 8 weeks, indicating the significant role of microporosity and nanofibrous architecture in bone regeneration.
可注射水凝胶作为组织再生支架具有优势，因为它们可以通过微创注射来递送，并与目标组织无缝集成。然而，当前可注射水凝胶的一个重要缺点是缺乏对其微观和纳米结构的同时控制。在本文中，作者报告了一种开发可注射水凝胶的策略，该水凝胶整合了纤维状纳米结构和多孔微结构。该水凝胶是通过使用新型纳米纤维微球作为构建块来制备的。基于蛋白质的纳米纤维微球是通过喷雾冷冻技术制造的，可以通过注射器-针头系统进行注射。可以部署细胞相容的光固化过程来连接微球并形成机械坚固的水凝胶支架。颗粒间的空隙形成相互连通的微孔，纳米纤维的直径（100-300nm）与天然细胞外基质的直径非常相似。与非多孔水凝胶和非纤维状水凝胶相比，微球退火纳米纤维（MANF）水凝胶在体外强烈增强人间充质干细胞的成骨标志物表达（ALP、Runx2、OCT 和 BSP）和矿化。MANF 水凝胶还促进细胞浸润并增强体内皮下植入模型中的新血管生成。在颅骨骨修复模型中研究了 MANF 水凝胶促进骨再生的能力。MANF 水凝胶在 8 周后显示出显著更高的骨再生，表明微孔和纳米纤维结构在骨再生中具有重要作用。
