OSTEOGENIC EXTRACELLULAR MATRIX SHEET FOR BONE TISSUE REGENERATION

OSTEOGENIC EXTRACELLULAR MATRIX SHEET FOR BONE TISSUE REGENERATION
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DOI:
10.22203/ecm.v036a06
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发表时间:
2018-07-01
影响因子:
3.1
通讯作者:
Tanaka, Y.
Tanaka, Y.
中科院分区:
工程技术2区
文献类型:
--
作者:
Onishi, T.;Shimizu, T.;Tanaka, Y.

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没有支架的细胞外基质(ECM)片在骨再生医学中的应用还没有广泛的报道。本研究的目的是证明成骨ECM片(OECMS)可以保持ECM的完整性和生长因子,以促进大鼠骨不连模型的骨形成。OECMS由成骨细胞片(OCS)制成。用酶联免疫吸附试验检测OECMS中胶原和生长因子[骨形态发生蛋白-2(BMP-2)、血管内皮生长因子(VFGFs)、碱性成纤维细胞生长因子(BFGF)和转化生长因子-β1(TGF-β1)]的浓度。接下来,将羟基磷灰石(HA)复合OECMS植入大鼠背部皮下,通过组织学评价其成骨能力。此外,将OECMS植入大鼠股骨骨不连模型中。雄性Fischer 344近交系大鼠18只,随机分为OECMS组和对照组。术后2、5、8周行放射学、组织学分析,8周行生物学分析,评价骨折愈合情况。OECMS中保留了I型胶原和生长因子。4周时,羟基磷灰石复合OECMS形成类骨质。OECMS组在5周和8周骨不连时骨再生增强。生物力学测试显示,8周时OECMS组的最大弯曲载荷显著高于对照组。结果表明,OECMS保留了骨形态发生蛋白-2和转化生长因子-β1,并具有良好的骨诱导和骨传导能力。因此,OECMS代表了一种潜在的无支架骨组织工程新材料。
The application of extracellular matrix (ECM) sheets without a scaffold is not extensively reported in bone regenerative medicine. The aim of the present study was to demonstrate that an osteogenic ECM sheet (OECMS) can retain ECM integrity and growth factors to enhance bone formation in a rat non-union model. The OECMS was produced from osteogenic cell sheets (OCS). Collagen and growth factor [bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factors (VFGFs), basic fibroblast growth factor (bFGF) and transforming growth factor beta 1 (TGF-(beta 1)] concentrations in the OECMS were quantified by enzyme-linked immunosorbent assay (ELISA). Next, hydroxyapatite (HA) constructs combined with OECMSs were implanted subcutaneously into the rats' backs to evaluate their osteoinductive capacity by histological evaluation. In addition, OECMSs were implanted in a rat femoral non-union model. 18 male Fischer 344 inbred rats were divided into OECMS and control groups. Fracture healing was evaluated by radiological and histological analyses at 2, 5 and 8 weeks and biological analysis at 8 weeks. Collagen I and growth factors were retained in the OECMSs. Osteoid formation was identified in the HA combined with OECMS at 4 weeks. Enhanced bone regeneration at the non-union of the OECMS group was confirmed at 5 and 8 weeks. Biomechanical testing revealed a significantly higher maximum bending load in the OECMS group as compared to the control group at 8 weeks. The results demonstrated that the OECMS retained BMP-2 and TGF-beta 1 and high osteoinductive and osteoconductive capacity. As such, the OECMS represents a potential new scaffold-free material for bone tissue engineering.