Qiu Yubei, Xu Xiaodong, Guo Weizhong, Zhao Yong, Su Jiehua, Chen Jiang
School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou 350002, China.
Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, China.
ACS Biomater Sci Eng. 2020 Apr 13;6(4):2323-2335. doi: 10.1021/acsbiomaterials.9b01954. Epub 2020 Mar 27.
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.
在骨再生领域，高效递送具有理想生物活性的骨形态发生蛋白-2（BMP-2）仍然是一项巨大挑战。在本研究中，制备了一种掺入负载BMP-2的介孔羟基磷灰石纳米颗粒（mHANPs）的丝素蛋白/壳聚糖支架（SCH-L）。在与丝素蛋白/壳聚糖复合材料混合之前，将BMP-2预加载到具有高比表面积的mHANPs上。同时研究了裸（不含BMP-2）丝素蛋白/壳聚糖/mHANP（SCH）支架和直接吸附有BMP-2的SCH支架（SCH-D）作为对照。体外释放动力学表明，与SCH-D支架相比，从SCH-L支架释放的BMP-2初始突释明显更低，随后随时间释放更持久。评估了体外细胞活力、骨髓间充质干细胞（BMSCs）的成骨分化以及支架在大鼠颅骨缺损中的体内成骨效果。结果表明，与裸SCH和SCH-D支架相比，SCH-L支架在体外显著促进了BMSCs的成骨分化，并在体内诱导了更明显的骨形成。进一步研究表明，如碱性磷酸酶（ALP）活性和矿化沉积试验所证实，mHANP介导的令人满意的构象变化和持续释放有利于保护释放的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，从而在成骨分化和骨诱导性方面很好地维持了其生物活性，这有助于显著提高SCH-L支架的体外和体内成骨效果。综上所述，这些结果提供了有力证据，表明mHANPs是将BMP-2结合到支架上的有吸引力的载体。SCH-L支架在骨组织再生应用中显示出有前景的潜力。
