Department of Orthopaedic Surgery, Xijing Hospital, The Air Force Medical University, Xi'an, Shaanxi 710032, People's Republic of China. These four authors contributed equally to this work.
Biomed Mater. 2020 Jul 27;15(5):055013. doi: 10.1088/1748-605X/ab8720.
Osteoporotic bone defects are a major challenge in clinics for bone regeneration. With the condition of osteoporosis, excessive bone absorption and impaired osteogenesis result in unexpectedly long healing procedures for defects. In order to simultaneously enhance bone formation and reduce bone resorption, a polydopamine-coated porous titanium scaffold was designed, to be integrated with anti-catabolic drug zoledronic acid nanoparticles (ZOL loaded gelatin NPs), which was able to achieve a local sustained release of ZOL as expected. The in vitro study demonstrated that extracts of the composite scaffolds would stimulate osteoblast differentiation; they also inhibited osteoclastogenesis at a ZOL loading concentration of 50 μmol l. In the subsequent in vivo study, the composite scaffolds were implanted into ovariectomy-induced osteoporotic rabbits suffering from femoral condyles defects. The results indicated that the composite scaffolds without ZOL loaded gelatin NPs only induced callus formation, mainly at the interface margin between the implant and bone, whereas the composite scaffolds with ZOL loaded gelatin NPs were capable of further enhancing osteogenesis and bone growth into the scaffolds. Moreover, the research proved that the promoting effect was optimal at a ZOL loading concentration of 50 μmol l. In summary, the present research indicated that a new type of porous titanium scaffold integrated with ZOL loaded gelatin NPs inherited a superior biocompatibility and bone regeneration capability. It would be an optimal alternative for the reconstruction of osteoporosis-related defects compared to a traditional porous titanium implant; in other words, the new type of scaffold offers a new effective and practical procedure option for patients suffering from osteoporotic bone defects.
骨质疏松性骨缺损是骨再生临床中的主要挑战。在骨质疏松症的情况下，过度的骨吸收和受损的成骨作用导致骨缺损的愈合过程出乎意料地延长。为了同时增强骨形成和减少骨吸收，设计了一种多巴胺涂层多孔钛支架，与抗分解代谢药物唑来膦酸纳米颗粒（载有唑来膦酸的明胶 NPs）结合，能够实现唑来膦酸的局部持续释放。体外研究表明，复合支架的提取物会刺激成骨细胞分化；在唑来膦酸浓度为 50μmol l 时，还能抑制破骨细胞生成。在随后的体内研究中，将复合支架植入去卵巢诱导的骨质疏松兔股骨髁缺损中。结果表明，不含载有唑来膦酸明胶 NPs 的复合支架仅诱导骨痂形成，主要在植入物与骨的界面边缘；而载有唑来膦酸明胶 NPs 的复合支架能够进一步增强成骨和骨生长进入支架。此外，研究证明，在唑来膦酸浓度为 50μmol l 时，促进效果最佳。综上所述，本研究表明，新型载有唑来膦酸明胶 NPs 的多孔钛支架具有优异的生物相容性和骨再生能力。与传统多孔钛植入物相比，它是治疗与骨质疏松相关的骨缺损的理想替代品；换句话说，新型支架为骨质疏松性骨缺损患者提供了一种新的有效且实用的治疗方案。
