Incorporation of a silicon-based polymer to PEG-DA templated hydrogel scaffolds for bioactivity and osteoinductivity
Incorporation of a silicon-based polymer to PEG-DA templated hydrogel scaffolds for bioactivity and osteoinductivity
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DOI：
10.1016/j.actbio.2019.09.018
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发表时间：
2019-11-01
影响因子：
9.7
通讯作者：
Grunlan, Melissa A.
中科院分区：
文献类型：
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作者：
Frassica, Michael T.;Jones, Sarah K.;Grunlan, Melissa A.
具有内在生物活性、骨诱导性和骨传导性的支架可以引导间充质干细胞（MSC）在缺乏外源性生长因子的情况下再生骨组织。先前，我们确定了通过甲基丙烯酸酯化的星星聚（二甲基硅氧烷）（PDMSstar-MA）与二丙烯酸酯化的聚（乙二醇）（PEG-DA）交联形成的水凝胶支架通过诱导羟基磷灰石形成（“生物活性”）促进骨结合，并促进MSC谱系向成骨细胞样命运发展（“骨诱导性”）。在本文中，我们将溶剂诱导相分离（SIPS）与熔盐模板组合以产生具有受控的PDMSstar-MA分布以及可调尺寸的互连大孔的PDMSstar-PEG水凝胶支架，以允许随后的细胞接种和新组织浸润（“骨传导”）。用两种数均分子量（M（n）s）（2k和7 k）的PDMSstar-MA制备支架，其中改变PDMSstar-MA：PEG-DA比率和模板盐尺寸。检查水凝胶内PDMSstar-MA的分布以及孔径、互连性百分比、动态和静态模量、水合作用、降解和体外生物活性（即，当暴露于模拟体液SBF时的矿化）。最后，使用接种的人骨髓源性MSC（hBMSC）的细胞培养物来确认无细胞毒性并表征骨诱导性。通过在制造期间利用特定盐尺寸的熔盐模板来实现可调谐的互连大孔。对于较低的Mn，PDMSstar-MA在PEG-DA基质中的分布得到改善，并导致特定材料性能（例如局部模量）和细胞反应的差异。然而，所有模板SIPSPDMSstar-PEG水凝胶被证实是生物活性的，无细胞毒性的，并显示PDMSstar-MA剂量依赖性的成骨作用。显著性声明一个组织工程支架，可以内在地引导间充质干细胞（MSC）再生骨组织，而不需要生长因子，将是一个更经济和安全的骨修复策略。通常，玻璃/陶瓷填料通过其诱导羟基磷灰石形成（“生物活性”）和促进MSC分化为成骨细胞样命运（“骨诱导性”）的能力来实现这一点。在此，我们已经制造了一种互连的大孔PEG-DA水凝胶支架，其利用PDMSstar-MA作为生物活性和骨诱导支架组分。我们能够证明这些PDMSstar-PEG水凝胶保持了骨修复的几个关键材料特性。此外，在人骨髓来源的MSC培养物中同时实现了生物活性和骨诱导性，这代表了完全基于材料的策略的显著成就。(C)2019 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
A scaffold that is inherently bioactive, osteoinductive and osteoconductive may guide mesenchymal stem cells (MSCs) to regenerate bone tissue in the absence of exogenous growth factors. Previously, we established that hydrogel scaffolds formed by crosslinking methacrylated star poly(dimethylsiloxane) (PDMSstar-MA) with diacrylated poly(ethylene glycol) (PEG-DA) promote bone bonding by induction of hydroxyapatite formation ("bioactive") and promote MSC lineage progression toward osteoblast-like fate ("osteoinductive"). Herein, we have combined solvent induced phase separation (SIPS) with a fused salt template to create PDMSstar-PEG hydrogel scaffolds with controlled PDMSstar-MA distribution as well as interconnected macropores of a tunable size to allow for subsequent cell seeding and neotissue infiltration ("osteoconductive"). Scaffolds were prepared with PDMSstar-MA of two number average molecular weights (M(n)s) (2k and 7k) with varying PDMSstar-MA:PEG-DA ratios and template salt sizes. The distribution of PDMSstar-MA within the hydrogels was examined as well as pore size, percent interconnectivity, dynamic and static moduli, hydration, degradation and in vitro bioactivity (i.e. mineralization when exposed to simulated body fluid, SBF). Finally, cell culture with seeded human bone marrow-derived MSCs (hBMSCs) was used to confirm non-cytotoxicity and characterize osteoinductivity. Tunable, interconnected macropores were achieved by utilization of a fused salt template of a specified salt size during fabrication. Distribution of PDMSstar-MA within the PEG-DA matrix improved for the lower Mn and contributed to differences in specific material properties (e.g. local modulus) and cellular response. However, all templated SIPS PDMSstar-PEG hydrogels were confirmed to be bioactive, non-cytotoxic and displayed PDMSstar-MA dose-dependent osteogenesis.Statement of SignificanceA tissue engineering scaffold that can inherently guide mesenchymal stem cells (MSCs) to regenerate bone tissue without growth factors would be a more cost-effective and safe strategy for bone repair. Typically, glass/ceramic fillers are utilized to achieve this through their ability to induce hydroxyapatite formation ("bioactive") and promote MSC differentiation to an osteoblast-like fate ("osteoinductive"). Herein, we have fabricated an interconnected, macroporous PEG-DA hydrogel scaffold that utilizes PDMSstar-MA as a bioactive and osteoinductive scaffold component. We were able to show that these PDMSstar-PEG hydrogels maintain several key material characteristics for bone repair. Further, bioactivity and osteoinductivity were simultaneously achieved in human bone marrow-derived MSC culture, representing a notable achievement for an exclusively material-based strategy. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.