Extracellular matrix (ECM) products have the potential to improve cellular attachment and promote tissue‐specific development by mimicking the native cellular niche. In this study, the therapeutic efficacy of an ECM substratum produced by bone marrow stem cells (BM‐MSCs) to promote bone regeneration in vitro and in vivo were evaluated. Fluorescence‐activated cell sorting analysis and phenotypic expression were employed to characterize the in vitro BM‐MSC response to bone marrow specific ECM (BM‐ECM). BM‐ECM encouraged cell proliferation and stemness maintenance. The efficacy of BM‐ECM as an adjuvant in promoting bone regeneration was evaluated in an orthotopic, segmental critical‐sized bone defect in the rat femur over 8 weeks. The groups evaluated were either untreated (negative control); packed with calcium phosphate granules or granules+BM‐ECM free protein and stabilized by collagenous membrane. Bone regeneration in vivo was analyzed using microcomputed tomography and histology. in vivo results demonstrated improvements in mineralization, osteogenesis, and tissue infiltration (114 ± 15% increase) in the BM‐ECM complex group from 4 to 8 weeks compared to mineral granules only (45 ± 21% increase). Histological observations suggested direct apposition of early bone after 4 weeks and mineral consolidation after 8 weeks implantation for the group supplemented with BM‐ECM. Significant osteoid formation and greater functional bone formation (polar moment of inertia was 71 ± 0.2 mm⁴ with BM‐ECM supplementation compared to 48 ± 0.2 mm⁴ in untreated defects) validated in vivo indicated support of osteoconductivity and increased defect site cellularity. In conclusion, these results suggest that BM‐ECM free protein is potentially a therapeutic supplement for stemness maintenance and sustaining osteogenesis.

中文翻译：

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使用骨特异性细胞外基质蛋白增强临界尺寸骨缺损的再生

细胞外基质 (ECM) 产品具有通过模仿天然细胞生态位来改善细胞附着并促进组织特异性发育的潜力。在本研究中，评估了骨髓干细胞（BM-MSC）产生的 ECM 培养基在体外和体内促进骨再生的治疗效果。采用荧光激活细胞分选分析和表型表达来表征体外 BM-MSC 对骨髓特异性 ECM (BM-ECM) 的反应。BM-ECM 促进细胞增殖和干性维持。在大鼠股骨的原位、节段性临界骨缺损中评估了 BM-ECM 作为促进骨再生的佐剂的功效，为期 8 周。评估的组要么未经治疗（阴性对照）；要么未经治疗（阴性对照）。填充有磷酸钙颗粒或颗粒+BM-ECM游离蛋白并由胶原膜稳定。使用微计算机断层扫描和组织学分析体内骨再生。体内结果表明，与仅使用矿物质颗粒（增加 45 ± 21%）相比，BM-ECM 复合物组在 4 至 8 周内矿化、成骨和组织浸润得到改善（增加 114 ± 15%）。组织学观察表明，补充 BM-ECM 的组在 4 周后直接植入早期骨，并在 8 周植入后进行矿物质固结。体内验证显着的类骨形成和更大的功能性骨形成（补充 BM-ECM 后的极惯性矩为 71 ± 0.2 mm ^{4 ，而未经治疗的缺损为 48 ± 0.2 mm 4}），表明支持骨传导性和增加缺损部位的细胞结构。总之，这些结果表明 BM-ECM 游离蛋白可能是维持干性和维持成骨的治疗补充剂。