Effects of cellular parameters on the in vitro osteogenic potential of dual-gelling mesenchymal stem cell-laden hydrogels.
Effects of cellular parameters on the in vitro osteogenic potential of dual-gelling mesenchymal stem cell-laden hydrogels.
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DOI：
10.1080/09205063.2016.1195157
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发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Mikos AG
中科院分区：
文献类型：
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作者：
Vo TN;Tabata Y;Mikos AG
本工作研究了细胞包封密度和分化阶段对由热凝胶化大分子单体和聚酰胺胺交联剂组成的可注射的双重物理和化学凝胶化水凝胶的成骨能力的影响。将未分化和成骨预分化的间充质干细胞（MSC）以6或15百万个细胞/mL的密度包封在具有明胶微粒的20重量%复合水凝胶内。我们假设高包封密度和预分化将促进细胞相互作用的增加并加速成骨，从而增强体外成骨潜力。水凝胶能够在28天的时间内保持包封细胞的活力，其中高包封密度和预分化组在所有时间点都具有最高的DNA含量。早期的碱性磷酸酶活性和矿化的包囊密度促进，而这种影响的预分化只观察到在低播种密度组。这两个参数仅表现出短暂的影响时，独立检查，但共同导致更高水平的碱性磷酸酶活性和矿化。综合效应表明，可能存在最佳的包封密度和分化期，需要研究以改善骨髓间充质干细胞用于骨组织工程中基于生物材料的治疗。
This work investigated the effects of cellular encapsulation density and differentiation stage on the osteogenic capacity of injectable, dual physically and chemically gelling hydrogels comprised of thermogelling macromers and polyamidoamine crosslinkers. Undifferentiated and osteogenically predifferentiated mesenchymal stem cells (MSCs) were encapsulated within 20 wt% composite hydrogels with gelatin microparticles at densities of 6 or 15 million cells/mL. We hypothesized that a high encapsulation density and predifferentiation would promote increased cellular interaction and accelerate osteogenesis, leading to enhanced osteogenic potential in vitro. Hydrogels were able to maintain the viability of the encapsulated cells over a period of 28 days, with the high encapsulation density and predifferentiation group possessing the highest DNA content at all timepoints. Early alkaline phosphatase activity and mineralization were promoted by encapsulation density, whereas this effect by predifferentiation was only observed in the low seeding density groups. Both parameters only demonstrated short-lived effects when examined independently, but jointly led to greater levels of alkaline phosphatase activity and mineralization. The combined effects suggest that there may be optimal encapsulation densities and differentiation periods that need to be investigated to improve MSCs for biomaterials-based therapeutics in bone tissue engineering.