Enhanced Osteogenic Activity and Bone Repair Ability of PLGA/MBG Scaffolds Doped with ZIF-8 Nanoparticles Loaded with BMP-2

Abstract

Rui Ma,1,* Yanwen Su,2,3,* Ruomu Cao,1 Kunzheng Wang,1 Pei Yang1 1Department of Bone and Joint Surgery, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shanxi, 710004, People’s Republic of China; 2State Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 3National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kunzheng Wang; Pei Yang, Email [email protected]; [email protected]: Tissue engineering scaffolds are porous and can be loaded with growth factors to promote osteogenesis and bone repair, which can solve the problem of clinical bone defects. The direct loading of growth factors on scaffolds is hindered by the disadvantages of low loading capacities, and uncontrollable burst release. Zeolitic imidazolate framework-8 (ZIF-8) has osteoinductive activity and drug-loading potential and can be loaded with growth factors to achieve sustained release. In this study, we aimed to establish a sustained release system of composite scaffolds loaded with growth factors to achieve the goal of slow controlled release and effective bone repair.Methods: ZIF‑8 nanoparticles loaded with bone morphogenetic protein-2 (BMP-2) were incorporated into poly-(lactide-co-glycolide)/mesoporous bioactive glass (PLGA/MBG) porous scaffolds by a 3D-printing method. The surface morphology, chemical properties and BMP-2 release of the prepared scaffold were investigated. The osteoblast adhesion, proliferation, spreading, and osteogenic differentiation in vitro and the bone repair ability in vivo of the PLGA/MBG/ZIF-8/BMP-2 (PMZB) scaffold were evaluated, and compared with those of PLGA/MBG (PM) and PLGA/MBG/ZIF-8 (PMZ) scaffolds.Results: The results showed that the PMZB scaffold exhibited a slow and continuous BMP-2 release pattern, enhanced osteoblast adhesion, proliferation, spreading and osteogenic differentiation in vitro, and promoted new bone formation and bone repair in vivo.Conclusion: The PLGA/MBG/ZIF-8/BMP-2 porous scaffold could continuously and slowly release BMP-2, enhance osteogenic activity, and promote new bone formation and bone repair at bone defects. The PMZB scaffold can be used as a bone graft material to repair bone defect at non-weight-bearing sites.Keywords: bone repair, controlled release, zeolitic imidazolate frameworks-8, mesoporous bioactive glass, scaffold

Keywords

• bone repair
• controlled release
• zeolitic imidazolate frameworks-8
• mesoporous bioactive glass
• scaffold