Off-the-Shelf Biomimetic Graphene Oxide-Collagen Hybrid Scaffolds Wrapped with Osteoinductive Extracellular Matrix for the Repair of Cranial Defects in Rats
Off-the-Shelf Biomimetic Graphene Oxide-Collagen Hybrid Scaffolds Wrapped with Osteoinductive Extracellular Matrix for the Repair of Cranial Defects in Rats
复制标题
现成的仿生氧化石墨烯-胶原蛋白混合支架包裹着骨诱导细胞外基质，用于修复大鼠颅骨缺损。
DOI：
10.1021/acsami.8b11071
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发表时间：
2018-12-12
影响因子：
9.5
通讯作者：
Wang, Zhenxing
中科院分区：
文献类型：
--
作者：
Liu, Shaokai;Mou, Shan;Wang, Zhenxing
水凝胶如I型胶原（COL）在骨组织修复中已被广泛研究，然而其较弱的机械强度限制了其临床应用。通过添加氧化石墨烯（GO）纳米片，研究人员成功地改善了水凝胶的机械性能和生物相容性。然而，对于大的骨缺损，GO杂化水凝胶的骨诱导和细胞粘附能力需要改进。间充质干细胞（Mesenchymal stem cell，MSC）分泌的细胞外基质（extracellular matrix，ECM）是一个复杂的网络，可以提供一个仿生的微环境和功能分子，促进细胞的增殖和存活。为了协同MSC-ECM与GO-COL混合植入物的优点，我们开发了一种新的ECM支架构建方法。首先，通过培养骨分化的骨髓间充质干细胞（BMSC）21天来产生骨诱导性细胞外基质（OiECM）。然后，用OiECM完全包裹GO-COL支架以构建用于植入的OiECM-GO-COL复合物。在体外和体内（5 mm大鼠颅骨缺损模型）评估了OiECM-GO-COL植入物的形态、物理性能、生物相容性和成骨性能。基因表达和细胞水平评估均表明，与COL或GO-COL组相比，OiECM-GO-COL植入物上培养的BMSC具有更高的增殖率和成骨能力。体内结果表明，OiECM-GO-COL植入物在大鼠临界颅骨缺损模型中获得了更好的修复效果，而其他组中的骨形成有限。这项研究提供了一个有前途的策略，大大提高了GO水凝胶的成骨能力和生物相容性，而无需在体外支架上接种和培养MSC，证明了其作为骨组织工程现成方法的潜力。
Hydrogels such as type I collagen (COL) have been widely studied in bone tissue repair, whereas their weak mechanical strength has limited their clinical application. By adding graphene oxide (GO) nanosheets, researchers have successfully improved the mechanical properties and biocompatibility of the hydrogels. However, for large bone defects, the osteoinductive and cell adhesion ability of the GO hybrid hydrogels need to be improved. Mesenchymal stem cell (MSC) secreted extracellular matrix (ECM), which is an intricate network, could provide a biomimetic microenvironment and functional molecules that enhance the cell proliferation and survival rate. To synergize the advantages of MSC-ECM with GO-COL hybrid implants, we developed a novel ECM scaffold construction method. First, an osteoinductive extracellular matrix (OiECM) was created by culturing osteodifferentiated bone marrow mesenchymal stem cells (BMSCs) for 21 days. Then, the GO-COL scaffold was fully wrapped with the OiECM to construct the OiECM-GO-COL composite for implantation. The morphology, physical properties, biocompatibility, and osteogenic performance of the OiECM-GO-COL implants were assessed in vitro and in vivo (5 mm rat cranial defect model). Both gene expression and cell level assessments suggested that the BMSCs cultured on OiECM-GO-COL implants had a higher proliferation rate and osteogenic ability compared to the COL or GO-COL groups. In vivo results showed that the OiECM-GO-COL implants achieved better repair effects in a rat critical cranial defect model, whereas bone formation in other groups was limited. This study provides a promising strategy, which greatly improves the osteogenic ability and biocompatibility of the GO hydrogels without the procedure of seeding and culturing MSCs on scaffolds in vitro, demonstrating its potential as an off-the-shelf method for bone tissue engineering.