Department of Biomaterials, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
ACS Appl Mater Interfaces. 2024 Sep 4;16(35):45956-45968. doi: 10.1021/acsami.4c08047. Epub 2024 Aug 25.
Osteoporotic bone defects are difficult to repair in elderly patients. This study aimed to repair osteoporotic bone defects using a combination of bone tissue engineering (BTE) and drug delivery systems (DDS). Herein, honeycomb granules (HCGs) composed of carbonate apatite microspheres were fabricated as BTE scaffolds. Each HCG possesses hexagonal macropores and abundant interconnected micropores between the microspheres. Owing to these multiscale interconnected pores, HCGs can readily contain antibodies against sclerostin (Scl), which causes imbalances in bone homeostasis. Anti-Scl antibody-loaded HCGs (Scl-Ab-HCGs) regulate the release of Scl-Abs in response to the pH of the osteoporotic environment. In ovariectomized rabbit osteoporotic femurs, HCG monotherapy forms new bone with less osteocyte damage (fewer empty bone lacunae) and fewer osteoclasts than osteoporotic bone; however, it is insufficient to prevent receptor activator of nuclear factor-kappa B ligand (RANKL) overexpression. Consequently, HCG monotherapy restores bone quantity better than no treatment but not to normal levels. In contrast, new bone tissue formed by Scl-Ab-HCG-based DDS predominantly expresses osteocalcin rather than RANKL, similar to normal bone, and shows a similar osteocyte apoptosis level, bone quantity, and osteoclast number as normal bone. Thus, Scl-Ab-HCG-based DDS is a promising approach for osteoporotic bone defect repair.
骨质疏松性骨缺损在老年患者中难以修复。本研究旨在结合骨组织工程（BTE）和药物传递系统（DDS）来修复骨质疏松性骨缺损。在此，我们制备了由碳酸磷灰石微球组成的蜂窝状颗粒（HCG）作为 BTE 支架。每个 HCG 都具有六方大孔和微球之间丰富的互联微孔。由于这些多尺度互联孔，HCG 可以轻易地容纳针对硬化蛋白（Scl）的抗体，而 Scl 会导致骨内稳态失衡。负载抗 Scl 抗体的 HCG（Scl-Ab-HCG）会根据骨质疏松环境的 pH 值调节 Scl-Abs 的释放。在去卵巢兔骨质疏松性股骨中，HCG 单药治疗形成新骨，其破骨细胞较少（骨陷窝空较少），骨细胞损伤也少于骨质疏松性骨；然而，其不足以防止核因子 κB 受体激活剂配体（RANKL）的过表达。因此，HCG 单药治疗在恢复骨量方面优于不治疗，但仍未恢复至正常水平。相比之下，基于 Scl-Ab-HCG 的 DDS 形成的新骨组织主要表达骨钙素而不是 RANKL，与正常骨相似，且骨细胞凋亡水平、骨量和破骨细胞数量与正常骨相似。因此，基于 Scl-Ab-HCG 的 DDS 是治疗骨质疏松性骨缺损的一种有前途的方法。
