Efficient delivery of bone morphogenetic protein-2 (BMP-2) with desirable bioactivity is still a great challenge in the field of bone regeneration. In this study, a silk fibroin/chitosan scaffold incorporated with BMP-2-loaded mesoporous hydroxyapatite nanoparticles (mHANPs) was prepared (SCH-L). BMP-2 was preloaded onto mHANPs with a high surface area before mixing with a silk fibroin/chitosan composite. Bare (without BMP-2) silk fibroin/chitosan/mHANP (SCH) scaffolds and SCH scaffolds with directly absorbed BMP-2 (SCH-D) were investigated in parallel for comparison. In vitro release kinetics indicated that BMP-2 released from the SCH-L scaffold showed a significantly lower initial burst release, followed by a more sustained release over time than the SCH-D scaffold. In vitro cell viability, osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and the in vivo osteogenic effect of scaffolds in a rat calvarial defect were evaluated. The results showed that compared with bare SCH and SCH-D scaffolds, the SCH-L scaffold significantly promoted the osteogenic differentiation of BMSCs in vitro and induced more pronounced bone formation in vivo. Further studies demonstrated that the mHANP-mediated satisfactory conformational change and sustained release benefited the protection of the released BMP-2 bioactivity, as confirmed by alkaline phosphatase (ALP) activity and a mineralization deposition assay. More importantly, the interaction of BMP-2/mHANPs enhanced the binding ability of BMP-2 to cellular receptors, thereby maintaining its biological activity in osteogenic differentiation and osteoinductivity well, which contributed to the markedly promoted in vitro and in vivo osteogenic efficacy of the SCH-L scaffold. Taken together, these results provide strong evidence that mHANPs represent an attractive carrier for binding BMP-2 to scaffolds. The SCH-L scaffold shows promising potential for bone tissue regeneration applications.

中文翻译：

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介孔羟基磷灰石纳米粒子介导BMP-2的释放和生物活性以增强骨再生。

具有理想的生物活性的骨形态发生蛋白2（BMP-2）的有效传递仍是骨再生领域的一大挑战。在这项研究中，制备了掺有BMP-2的中孔羟基磷灰石纳米粒子（mHANPs）的丝素蛋白/壳聚糖支架（SCH-L）。将BMP-2预加载到高表面积的mHANP上，然后再与丝素蛋白/壳聚糖复合材料混合。平行研究裸露的（无BMP-2）丝素蛋白/壳聚糖/ mHANP（SCH）支架和具有直接吸收的BMP-2（SCH-D）的SCH支架以进行比较。体外释放动力学表明，从SCH-L支架中释放的BMP-2表现出明显较低的初始突释释放，随后随时间的推移比SCH-D支架更持久地释放。体外细胞活力 评价了骨髓间充质干细胞（BMSCs）的成骨分化，以及支架在大鼠颅盖缺损中的体内成骨作用。结果表明，与裸露的SCH和SCH-D支架相比，SCH-L支架在体外显着促进BMSCs的成骨分化，并在体内诱导更明显的骨形成。进一步的研究表明，如碱性磷酸酶（ALP）活性和矿化沉积测定所证实的，mHANP介导的令人满意的构象变化和持续释放有益于保护释放的BMP-2生物活性。更重要的是，BMP-2 / mHANPs的相互作用增强了BMP-2与细胞受体的结合能力，从而很好地保持了其在成骨分化和骨诱导性方面的生物学活性，其显着促进了SCH-L支架的体外和体内成骨功效。两者合计，这些结果提供了有力的证据，证明mHANPs是将BMP-2与支架结合的有吸引力的载体。SCH-L支架在骨组织再生应用中显示出有希望的潜力。