Department of Bioengineering, University of California-San Diego, San Diego, CA, USA.
Biomaterials Research Centre, Korea Institute of Science and Technology, Seoul, Republic of Korea.
Eur Cell Mater. 2013 Jan 18;25:114-129. doi: 10.22203/ecm.v025a08.
Design of macroporous synthetic grafts that can promote infiltration of cells, their differentiation, and synthesis of bone-specific extracellular matrix is a key determinant for in vivo bone tissue regeneration and repair. In this study, we investigated the effect of the microarchitecture of the scaffold on osteogenic differentiation of human mesenchymal stem cells (hMSCs). Poly(ethylene glycol) diacrylate-co-N-acryloyl 6-aminocaproic acid cryogels were fabricated to have either a pore network consisting of cellular, randomly oriented pores (termed 'spongy') or a pore network consisting of lamellar columns (termed 'columnar'), with both cryogel types showing a similar porosity. Both spongy and columnar cryogels supported comparable levels of cell viability and proliferation of hMSCs in vitro. However, spongy cryogels promoted osteogenic differentiation to a greater extent than their columnar counterparts, as evidenced by increased alkaline phosphatase activity and osteoblastic gene expression over 21 days post culture. Leveraging upon our previous work, we further evaluated the ability of these synthetic scaffolds in conjunction with mineralisation to promote ectopic bone formation upon subcutaneous implantation in nude rats. Mineralised spongy and columnar cryogels, both in the presence and absence of exogenous hMSCs, promoted ectopic bone formation in vivo. No such bone formation was observed in acellular cryogels devoid of mineralisation, with extensive host cell infiltration and vascularisation in columnar cryogels, and negligible infiltration into spongy cryogels. Our results thus present a novel method to tune the microarchitecture of porous polymeric scaffolds, in addition to suggesting their efficacy as synthetic bone grafts.
设计能够促进细胞浸润、分化以及合成骨特异性细胞外基质的大孔合成移植物是体内骨组织再生和修复的关键决定因素。在这项研究中，我们研究了支架的微观结构对人骨髓间充质干细胞（hMSCs）成骨分化的影响。聚乙二醇二丙烯酸酯-co-N-丙烯酰基 6-氨基己酸冷冻凝胶被制成具有由细胞组成的、随机定向孔的孔网络（称为“海绵状”）或由层状柱组成的孔网络（称为“柱状”），这两种冷冻凝胶类型均具有相似的孔隙率。海绵状和柱状冷冻凝胶都支持 hMSC 的体外存活和增殖水平相当。然而，海绵状冷冻凝胶比其柱状对应物更能促进成骨分化，这表现在碱性磷酸酶活性和骨细胞基因表达在培养 21 天后增加。利用我们之前的工作，我们进一步评估了这些合成支架与矿化相结合的能力，以促进裸鼠皮下植入后异位骨形成。矿化的海绵状和柱状冷冻凝胶，无论是在存在还是不存在外源性 hMSC 的情况下，都能在体内促进异位骨形成。在缺乏矿化的无细胞冷冻凝胶中没有观察到这种骨形成，在柱状冷冻凝胶中有大量的宿主细胞浸润和血管化，而在海绵状冷冻凝胶中浸润很少。因此，我们的研究结果提出了一种新的方法来调节多孔聚合物支架的微观结构，并表明其作为合成骨移植物的功效。
