In this paper, we demonstrate a strategy of covalently bonding bioactive molecules onto inorganic hydroxyapatite (HAp) to improve the compatibility between organic and inorganic components and endow the bone composites with sustainable bioactivity. Bone morphogenetic protein-2 (BMP-2) peptide covalently immobilized nano-hydroxyapatite (nHAp-BMP-2) is developed to preserve the bioactivity and slow the release of the BMP-2 peptide. Then nHAp-BMP-2 was further incorporated into an ultraviolet-curable mixture of gelatin methacrylamide (GelMA) and four-armed PEG methacrylamide (four-armed PEGMA) to form a Gel/(nHAp-BMP-2) composite. The hydrogen bonding between gelatin and BMP-2 on nHAp-BMP-2 enhanced the compatibility between inorganic and organic components. The Gel/(nHAp-BMP-2) composite exhibited superior biocompatibility caused by gelatin and nHAp-BMP-2, except in a two-dimensional cell culture, the hydrogel was also capable of a three-dimensional cell culture. In addition, the introduction of nHAp-BMP-2 had a positive influence on bone marrow mesenchymal stem cell proliferation, differentiation, and the subsequent calcification on the composite. After treatment of a rat calvarial defect model for 12 weeks, the Gel/(nHAp-BMP-2) group showed the largest new bone volume and the highest ratio of new bone (50.54 ± 13.51 mm³ and 64.38 ± 17.22%, respectively) compared to those of the other groups. These results demonstrate that this way of controlling BMP-2 release is effective and the Gel/(nHAp-BMP-2) composite has great potential in bone regeneration therapy.

中文翻译：

---

有效地再生骨骼的有机/无机相容和可持续生物活性复合材料的开发

在本文中，我们演示了一种将生物活性分子共价键合到无机羟基磷灰石（HAp）上的策略，以提高有机和无机组分之间的相容性，并使骨骼复合材料具有可持续的生物活性。共价固定的骨形态发生蛋白2（BMP-2）肽纳米羟基磷灰石（nHAp-BMP-2）被开发以保留生物活性并减缓BMP-2肽的释放。然后将nHAp-BMP-2进一步掺入明胶甲基丙烯酰胺（GelMA）和四臂PEG甲基丙烯酰胺（四臂PEGMA）的紫外线可固化混合物中，以形成Gel /（nHAp-BMP-2）复合材料。明胶和BMP-2在nHAp-BMP-2上的氢键作用增强了无机和有机组分之间的相容性。Gel /（nHAp-BMP-2）复合材料表现出由明胶和nHAp-BMP-2引起的优异的生物相容性，除了在二维细胞培养中，水凝胶还能够在三维细胞培养中使用。此外，nHAp-BMP-2的引入对骨髓间充质干细胞的增殖，分化以及随后对复合物的钙化有积极影响。治疗大鼠颅骨缺损模型12周后，Gel /（nHAp-BMP-2）组显示出最大的新骨体积和最高的新骨比例（50.54±13.51 mm 以及随后在复合材料上的钙化。治疗大鼠颅骨缺损模型12周后，Gel /（nHAp-BMP-2）组显示出最大的新骨体积和最高的新骨比例（50.54±13.51 mm 以及随后在复合材料上的钙化。治疗大鼠颅骨缺损模型12周后，Gel /（nHAp-BMP-2）组显示出最大的新骨体积和最高的新骨比例（50.54±13.51 mm^分别为3和64.38±17.22％）。这些结果表明，这种控制BMP-2释放的方法是有效的，并且Gel /（nHAp-BMP-2）复合材料在骨再生治疗中具有巨大的潜力。