Recombinant PTH modification: A new strategy for a multifunctional CaP material to enhance bone regeneration
Recombinant PTH modification: A new strategy for a multifunctional CaP material to enhance bone regeneration
复制标题
重组PTH修饰：多功能CaP材料增强骨再生的新策略
DOI：
10.1016/j.compositesb.2022.110289
复制
发表时间：
2022-09-20
影响因子：
13.1
通讯作者：
Cai，Lin
中科院分区：
文献类型：
--
作者：
Wang，Yi;Hao，Zhuowen;Cai，Lin
骨再生需要骨生成、骨溶解和血管生成的相互作用以及适当的免疫微环境。重组人甲状旁腺激素（PTH 1 -34）因其良好的成骨活性、破骨细胞生成和血管生成而被批准用于临床抗骨质疏松治疗。然而，净骨吸收现象限制了其在局部骨修复中的应用。我们的小组提供了一个有效的策略，多功能磷酸钙（CaP）陶瓷与调制M1巨噬细胞促炎作用，骨再生。CaP陶瓷支架具有甲状旁腺激素相关肽-1（PTHrP-1）功能，用于骨缺损修复。首先，肽功能化的真骨陶瓷（TBC）支架表现出有限的M1巨噬细胞促炎作用，以改善成骨微环境。第二，PTHrP-1保留了PTH 1 -34的成骨活性和血管生成特性，同时下调破骨细胞活性以诱导有利的骨形成。第三，通过三连续天冬氨酸（D3）和丝氨酸磷酸化（PSer）修饰的肽对天然CaP基质具有高亲和力，实现了PTHrP-1在TBC支架中的缓慢释放。第四，天冬氨酸的羧基与钙结合，有效地促进羟基磷灰石（HAP）成核，完成自组装矿化。有利于骨再生。结果表明，PTHrP-1-TBC比单独的TBC支架和未修饰的肽更适合于骨再生。
Bone regeneration requires the interaction of osteogenesis, osteolysis, and angiogenesis as well as an appropriate immune microenvironment. Recombinant human parathyroid hormone (PTH1-34) is approved for clinical anti-osteoporosis treatment because of its good osteogenic activity, osteoclastosis, and angiogenesis. However, the phenomenon of net bone resorption limits its use in local bone repair. Our group provides an effective strategy for multifunctional calcium phosphate (CaP) ceramics with modulating M1 macrophage pro-inflammatory effects, and bone regeneration. CaP ceramic scaffold is functionalized with parathyroid hormone related peptide-1 (PTHrP-1) for bone defect repair. First, peptide-functionalized true bone ceramic (TBC) scaffold exhibit limited M1 macrophage pro-inflammatory effects to improve the osteogenic microenvironment. Second, PTHrP-1 retains the osteogenic activity and angiogenic properties of PTH1-34 while downregulating osteoclast activity to induce favorable bone formation. Third, the peptide modified by tri-continuous aspartic acids (D3) and serine phosphorylation (PSer) has high affinity to the natural CaP matrix, achieving a slow release of PTHrP-1 in the TBC scaffold. Fourth, the carboxyl group of aspartate combined with calcium effectively promotes hydroxyapatite (HAP) nucleation and completes self-assembled mineralization. which is beneficial for bone regeneration. The results show that PTHrP-1-TBC is more suitable for bone regeneration than TBC scaffold and unmodified peptide alone.