This is the first report on the development of a covalently bone morphogenetic protein-2 (BMP2)-immobilized hydrogel that is suitable for osteogenic differentiation of human periodontal ligament stem cells (hPLSCs). O-propargyl-tyrosine (OpgY) was site-specifically incorporated into BMP2 to prepare BMP2-OpgY with an alkyne group. The engineered BMP2-OpgY exhibited osteogenic characteristics after in vitro osteogenic differentiation of hPLSCs, indicating the osteogenic ability of BMP2-OpgY. A methoxy polyethylene glycol-(polycaprolactone-(N3)) block copolymer (MC-N3) was prepared as an injectable in situ-forming hydrogel. BMP2 covalently immobilized on an MC hydrogel (MC-BMP2) was prepared quantitatively by a simple biorthogonal reaction between alkyne groups on BMP2-OpgY and azide groups on MC-N3 via a Cu(I)-catalyzed click reaction. The hPLSCs-loaded MC-BMP2 formed a hydrogel almost immediately upon injection into animals. In vivo osteogenic differentiation of hPLSCs in the MC-BMP2 formulation was confirmed by histological staining and gene expression analyses. Histological staining of hPLSC-loaded MC-BMP2 implants showed evidence of mineralized calcium deposits, whereas hPLSC-loaded MC-Cl or BMP2-OpgY mixed with MC-Cl, implants showed no mineral deposits. Additionally, MC-BMP2 induced higher levels of osteogenic gene expression in hPLSCs than in other groups. In conclusion, BMP2-OpgY covalently immobilized on MC-BMP2 induced osteogenic differentiation of hPLSCs as a noninvasive method for bone tissue engineering.

译文

这是关于共价骨形态发生蛋白2 (BMP2) 固定化水凝胶的开发的第一份报告,该水凝胶适用于人牙周膜干细胞 (hPLSCs) 的成骨分化。将O-炔丙基-酪氨酸 (OpgY) 位点特异性掺入BMP2中以制备具有炔基的BMP2-OpgY。工程BMP2-OpgY在hPLSCs体外成骨分化后表现出成骨特性,表明BMP2-OpgY的成骨能力。制备甲氧基聚乙二醇-(聚己内酯-(N3)) 嵌段共聚物 (MC-N3) 作为可注射原位形成水凝胶。通过Cu(I) 催化的点击反应,通过BMP2-OpgY上的炔烃基团与MC-N3上的叠氮化物基团之间的简单双正交反应,定量地制备共价固定在MC水凝胶 (MC-BMP2) 上的BMP2。负载hPLSCs的MC-BMP2在注射到动物中几乎立即形成水凝胶。通过组织学染色和基因表达分析证实了MC-BMP2制剂中hPLSCs的体内成骨分化。hPLSC负载的MC-BMP2植入物的组织学染色显示出矿化钙沉积的证据,而hPLSC负载的MC-Cl或BMP2-OpgY与MC-Cl混合,植入物未显示出矿物质沉积。此外,与其他组相比,MC-BMP2在hPLSCs中诱导了更高水平的成骨基因表达。总之,共价固定在MC-BMP2上的BMP2-OpgY可诱导hPLSCs的成骨分化,作为骨组织工程的非侵入性方法。

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