Large bone defects in long bones pose a significant clinical challenge due to the lack of suitable grafts. Recently, decellularized bone matrix has drawn attention, since it can be used as a bioactive ingredient to fabricate scaffolds for bone regeneration. However, residual DNA in the decellularized matrix is a potential hindrance that can trigger an immunogenic rejection. We hypothesized that extraction of the extracellular matrix (ECM), with low DNA contents, and its subsequent conversion to a microsphere could be an ideal strategy to exploit the structural and molecular cues that exist within the ECM. In this study, we derived a decellularized bone matrix with negligible DNA contents to prepare microspheres. We further functionalized the microsphere with nano-hydroxyapatite and metformin hydrochloride (MF) to enhance its inherent bioactivity. The fabrication and subsequent physicochemical characterization revealed that the composite microspheres were successfully furnished with suitable physicochemical properties. Biological evaluation of microspheres revealed a positive correlation between bioactive microspheres and osteogenic proliferation and differentiation. In vivo experiments further demonstrated the potential of microspheres to contract the bone with the highly dense and organized bone matrix. Hence, the microsphere could be a potential candidate for repairing large bone defects.

中文翻译：

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纳米羟基磷灰石复合光交联骨脱细胞基质微球的开发


由于缺乏合适的移植物，长骨中的大骨缺损构成了重大的临床挑战。最近，脱细胞的骨基质引起了人们的关注，因为它可以用作生物活性成分来制造骨再生支架。然而，脱细胞基质中的残留 DNA 是可能触发免疫原性排斥反应的潜在障碍。我们假设提取 DNA 含量低的细胞外基质 （ECM） 并随后转化为微球可能是利用 ECM 中存在的结构和分子线索的理想策略。在这项研究中，我们衍生了一种 DNA 含量可以忽略不计的脱细胞骨基质来制备微球。我们进一步用纳米羟基磷灰石和盐酸二甲双胍 （MF） 对微球进行功能化，以增强其固有的生物活性。制备和随后的物理化学表征表明，复合微球成功地赋予了合适的物理化学性质。微球的生物学评价显示，生物活性微球与成骨增殖和分化呈正相关。体内实验进一步证明了微球与高密度和有序的骨基质一起收缩骨骼的潜力。因此，微球可能是修复大骨缺损的潜在候选者。