<b>Efficacy of BMP-2 Peptide-modified Nano-hydroxyapatite Alginate Hydrogel in Vertebral Bone Defect Repair</b>

For the effective treatment of vertebral bone defects (BDs), we constructed an innovative hydroxyapatite nanoparticle (HAP)-hyaluronic acid (HA)-alginate (ALG) scaffold loaded with bone morphogenetic protein-2 (BMP-2). The particle size of HAP was around 80–100 nm, and its addition markedly reduced the swelling rate and degradability of the HA-ALG scaffold while enhancing its compression resistance, enabling it to better support the BD site and provide a good proliferation environment for osteoblasts. Furthermore, HAP-HA-ALG effectively extended the half-life of BMP-2 by nearly 50 fold, allowing it to exert its osteogenic effects more consistently. In cellular experiments, we found that BMP-2@HAP-HA-ALG significantly enhanced the activity and migration ability of bone marrow mesenchymal stromal cells (BMSCs), as well as the expression level of related osteogenic proteins in cells, which better exerted osteoinductive and osteoconductive functions. In animal tests, BMP-2@HAP-HA-ALG could better facilitate the generation of new bone and bone trabecula at BD sites and markedly enhance the bone density level, thus shortening the repair time of BDs. Therefore, BMP-2@HAP-HA-ALG shows great potential in the restoration of vertebral BDs.为实现椎体骨缺损（vertebral bone defects，BDs）的有效治疗，本研究构建了一种负载骨形态发生蛋白2（bone morphogenetic protein-2，BMP-2）的新型羟基磷灰石纳米颗粒（hydroxyapatite nanoparticle，HAP）-透明质酸（hyaluronic acid，HA）-海藻酸盐（alginate，ALG）复合支架。该HAP的粒径约为80~100 nm，其掺入可显著降低HA-ALG支架的溶胀率与降解性能，同时提升其抗压强度，使其能够更好地支撑椎体骨缺损部位，并为成骨细胞提供优良的增殖微环境。此外，HAP-HA-ALG复合支架可将BMP-2的半衰期延长近50倍，使其成骨效应得以更持久稳定地发挥。在细胞实验中，研究发现BMP-2@HAP-HA-ALG可显著增强骨髓间充质基质细胞（bone marrow mesenchymal stromal cells，BMSCs）的活性与迁移能力，同时上调细胞内相关成骨蛋白的表达水平，进而更好地发挥骨诱导与骨传导功能。在动物实验中，BMP-2@HAP-HA-ALG可更有效地促进椎体骨缺损部位新生骨与骨小梁的生成，并显著提升骨密度水平，从而缩短椎体骨缺损的修复周期。因此，BMP-2@HAP-HA-ALG在椎体骨缺损修复领域展现出巨大的应用潜力。