Development of demineralized bone matrix-based implantable and biomimetic microcarrier for stem cell expansion and single-step tissue-engineered bone graft construction
Development of demineralized bone matrix-based implantable and biomimetic microcarrier for stem cell expansion and single-step tissue-engineered bone graft construction
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开发基于脱矿骨基质的可植入仿生微载体，用于干细胞扩增和单步组织工程骨移植构建
DOI：
10.1039/c6tb02414a
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发表时间：
2017-01-07
影响因子：
7
通讯作者：
Zhang, Zhi-Yong
中科院分区：
文献类型：
--
作者：
Wang, Zhenxing;Wu, Dingyu;Zhang, Zhi-Yong
Tissue engineered bone grafts (TEBG) using mesenchymal stem cells (MSCs) demonstrate great potential for bone defect treatment. However, current MSC expansion techniques and multiple-step TEBG construction strategy have problems such as repeated trypsinization, limiting further clinical application. Microcarriers present promising solutions, but conventional microcarriers are either non-implantable or have insufficient biomimetic potential to maintain effective cellular function. Here, we developed a biomimetic and implantable microcarrier using demineralized bone matrix (DBM-MC), which preserves the essential biochemical composition, architecture and surface topography of natural bone tissue. Furthermore, based on this DBM-MC, we established a single-step micro-sized TEBG (mu TEBG) construction strategy integrating multiple procedures of cell seeding, expansion, and differentiation. Benchmarked with Cytodex 3, a widely used microcarrier, DBM-MC shared similar physical properties, and supported efficient cell adhesion and proliferation with MSC characteristics being well maintained. However, when implanted ectopically, the MSC/DBM-MC constructs achieved more neo-bone formation with better vascularization than MSC/Cytodex 3. Moreover, mTEBG generated via our single-step strategy can successfully heal a critical-sized cranial defect with two-fold more bone regeneration. This new DBM-MC and single-step mTEBG construction strategy can provide an enclosed, large-scale, reduced-trypsinization, and semi-automatic fabrication process to generate mu TEBGs with outstanding osteogenic and angiogenic capacity, demonstrating great potential for clinical application.
