A nano-scaled and multi-layered recombinant fibronectin/cadherin chimera composite selectively concentrates osteogenesis-related cells and factors to aid bone repair
A nano-scaled and multi-layered recombinant fibronectin/cadherin chimera composite selectively concentrates osteogenesis-related cells and factors to aid bone repair
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纳米级多层重组纤连蛋白/钙粘蛋白嵌合复合材料选择性浓缩成骨相关细胞和因子以帮助骨修复
DOI：
10.1016/j.actbio.2017.02.016
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发表时间：
2017
影响因子：
9.7
通讯作者：
Luo Fei
中科院分区：
文献类型：
--
作者：
Xing Junchao;Mei Tieniu;Luo Keyu;Li Zhiqiang;Yang Aijun;Li Zhilin;Xie Zhao;Zhang Zehua;Dong Shiwu;Hou Tianyong;Xu Jianzhong;Luo Fei
临床上迫切需要方便、有效的骨移植。选择性细胞保留（SCR）策略，通过其将成骨相关细胞和因子从骨髓富集到生物支架中，具有很大的前景。然而，保留功效受到骨髓中成骨相关细胞和因子的相对低密度的限制;此外，缺乏令人满意的支架表面改性剂进一步加剧了困境。为了解决这个问题，通过逐层自组装技术（LBL-rFN/CDH）建立了由重组纤连蛋白/钙粘蛋白嵌合体组成的多层构建体，并用于修饰脱矿骨基质（DBM）支架。经验证，该改性方法稳定有效。通过物理拦截和更重要的化学识别（纤连蛋白/整联蛋白）机制，LBL-rFN/CDH修饰显著改善了对成骨相关细胞的保留效力和选择性，例如，单核细胞、间充质干细胞（MSC）和造血干细胞（HSC），以及生物活性因子，例如，bFGF、BMP-2和SDF-1α。此外，所得到的复合物（命名为DBM-LBL-rFN/CDH）不仅在SCR后表现出强大的MSC募集能力，而且还为MSC的增殖和成骨分化提供了有利的微环境。最终，骨修复得到明显改善。总的来说，DBM-LBL-rFN/CDH为SCR提供了一种合适的生物材料，并为巨大的骨移植需求提供了一种有前途的解决方案。选择性细胞保留（SCR）技术集成骨、骨诱导和骨传导于一体，为开发理想的骨移植物带来了希望。然而，它受到低效率和低选择性的限制。因此，我们用纳米级和多层的重组纤连蛋白/钙粘蛋白嵌合体（DBM-rFN/CDH-LBL）修饰脱钙骨基质，并评价其对SCR和骨修复的影响。DBM-rFN/CDH-LBL通过物理拦截和化学识别显著提高了SCR的效率和选择性。富集后的DBM-rFN/CDH-LBL为MSCs的迁移、增殖和成骨分化提供了良好的微环境，从而促进骨修复。DBM-rFN/CDH-LBL是一种新型的生物材料，具有成本效益高，储存和运输方便，可在术中快速构建等优点。
Easily accessible and effective bone grafts are in urgent need in clinic. The selective cell retention (SCR) strategy, by which osteogenesis-related cells and factors are enriched from bone marrow into bio-scaffolds, holds great promise. However, the retention efficacy is limited by the relatively low densities of osteogenesis-related cells and factors in marrow; in addition, a lack of satisfactory surface modifiers for scaffolds further exacerbates the dilemma. To address this issue, a multi-layered construct consisting of a recombinant fibronectin/cadherin chimera was established via a layer-by-layer self-assembly technique (LBL-rFN/CDH) and used to modify demineralised bone matrix (DBM) scaffolds. The modification was proven stable and effective. By the mechanisms of physical interception and more importantly, chemical recognition (fibronectin/integrins), the LBL-rFN/CDH modification significantly improved the retention efficacy and selectivity for osteogenesis-related cells, e.g., monocytes, mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs), and bioactive factors, e.g., bFGF, BMP-2 and SDF-1α. Moreover, the resulting composite (designated as DBM-LBL-rFN/CDH) not only exhibited a strong MSC-recruiting capacity after SCR, but also provided favourable microenvironments for the proliferation and osteogenic differentiation of MSCs. Eventually, bone repair was evidently improved. Collectively, DBM-LBL-rFN/CDH presented a suitable biomaterial for SCR and a promising solution for tremendous need for bone grafts.Statement of SignificanceThere is an urgent need for effective bone grafts. With the potential of integrating osteogenicity, osteoinductivity and osteoconductivity, selective cell retention (SCR) technology brings hope for developing ideal grafts. However, it is constrained by low efficacy and selectivity. Thus, we modified demineralized bone matrix with nano-scaled and multi-layered recombinant fibronectin/cadherin chimera (DBM-rFN/CDH-LBL), and evaluate its effects on SCR and bone repair. DBM-rFN/CDH-LBL significantly improved the efficacy and selectivity of SCR via physical interception and chemical recognition. The post-enriched DBM-rFN/CDH-LBL provided favourable microenvironments to facilitate the migration, proliferation and osteogenic differentiation of MSCs, thus accelerating bone repair. Conclusively, DBM-rFN/CDH-LBL presents a novel biomaterial with advantages including high cost-effectiveness, more convenience for storage and transport and can be rapidly constructed intraoperatively.