Smart Hydrogels for the Augmentation of Bone Regeneration by Endogenous Mesenchymal Progenitor Cell Recruitment
Smart Hydrogels for the Augmentation of Bone Regeneration by Endogenous Mesenchymal Progenitor Cell Recruitment
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DOI：
10.1002/advs.201903395
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发表时间：
2020-02-05
期刊：
影响因子：
15.1
通讯作者：
Ehrbar, Martin
中科院分区：
文献类型：
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作者：
Lienemann, Philipp S.;Vallmajo-Martin, Queralt;Ehrbar, Martin
用重组骨形态发生蛋白-2（BMP-2）治疗骨缺损需要高剂量，妨碍了广泛的临床应用。在这里，提出了一种生物工程方法，通过动员愈合相关的间充质祖细胞（MPCs），大大提高了低剂量BMP-2为基础的骨再生。智能合成水凝胶用于捕获和研究内源性MPC向骨缺损的运输。水凝胶捕获和前瞻性分离的MPC在体外分化成多个谱系，并在体内形成骨。体外筛选表明，血小板衍生生长因子BB（PDGF-BB）强烈招募预期的MPC，使其成为一个有前途的候选人的工程水凝胶，丰富内源性MPC在体内。然而，PDGF-BB在体外和体内均抑制BMP-2介导的骨生成。相比之下，具有PDGF-BB的快速释放和BMP-2的持续递送的智能双向动态释放水凝胶有益地促进骨缺损的愈合。总的来说，它表明，通过智能合成水凝胶调节体内内源性祖细胞的动力学显着改善骨愈合，并在再生医学的其他先进应用中具有巨大的潜力。
The treatment of bone defects with recombinant bone morphogenetic protein-2 (BMP-2) requires high doses precluding broad clinical application. Here, a bioengineering approach is presented that strongly improves low-dose BMP-2-based bone regeneration by mobilizing healing-associated mesenchymal progenitor cells (MPCs). Smart synthetic hydrogels are used to trap and study endogenous MPCs trafficking to bone defects. Hydrogel-trapped and prospectively isolated MPCs differentiate into multiple lineages in vitro and form bone in vivo. In vitro screenings reveal that platelet-derived growth factor BB (PDGF-BB) strongly recruits prospective MPCs making it a promising candidate for the engineering of hydrogels that enrich endogenous MPCs in vivo. However, PDGF-BB inhibits BMP-2-mediated osteogenesis both in vitro and in vivo. In contrast, smart two-way dynamic release hydrogels with fast-release of PDGF-BB and sustained delivery of BMP-2 beneficially promote the healing of bone defects. Collectively, it is shown that modulating the dynamics of endogenous progenitor cells in vivo by smart synthetic hydrogels significantly improves bone healing and holds great potential for other advanced applications in regenerative medicine.