JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE) ›› 2020, Vol. 40 ›› Issue (09): 1184-1192.doi: 10.3969/j.issn.1674-8115.2020.09.004

• Original article (Basic research) • Previous Articles     Next Articles

Injectable hydrogel loaded with bone morphogenetic protein-2 microspheres for bacteriostasis and osteogenesis

LIU Li-li1, CUI Wen-guo1, 2   

  1. 1. College of Pharmaceutical Sciences, Soochow University, Suzhou 215000, China; 2. Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Disease, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Online:2020-09-28 Published:2020-11-04
  • Supported by:
    National Natural Science Foundation of China (51873107); Shanghai Talent Development Fund (2018099); Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (20171906); Shanghai Jiao Tong University “Medical and Research” Program (ZH2018ZDA04).

Abstract: Objective · To construct a novel antibacterial and injectable hydrogel (BMP/Gel/SH-Ag) loaded with bone morphogenetic protein-2 (BMP-2) microspheres, and investigate its biocompatibility, antibacterial properties and bone-promoting properties. Methods · The photocrosslinked gelatin microspheres loaded with BMP-2 were prepared by microfluidics. The microspheres were mixed with 4-arm thiol-terminated poly (ethylene glycol) (4SH-PEG) and crosslinked with Ag+ to prepare injectable sulfhydrylated PEG hydrogels (BMP/Gel/SH-Ag). The micromorphology of microspheres and hydrogels was observed by light microscope and scanning electron microscope. The drug release profile was investigated at 37 ℃ in a shaker (100 r/min). The injectability of BMP/Gel/SH-Ag was evaluated by injecting hydrogel using a syringe with a tip diameter of 0.5 mm. The antibacterial activity of BMP/Gel/SH-Ag against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was evaluated by agar diffusion test. The biocompatibility of BMP/Gel/SH-Ag was verified by CCK-8, and the bone-promoting activity was evaluated by alkaline phosphatase (ALP) assay and calcium nodule staining in bone marrow mesenchymal stem cells (BMSCs). Results · Gelatin microspheres had smooth appearance and uniform particle size distribution (~ 350 μm). BMP/Gel/SH-Ag had porous microstructure and can be injected with a syringe needle with a diameter of up to 0.5 mm in diameter to produce hydrogel filament. The cumulative release of BMP-2 from BMP/Gel/SH-Ag was (81.8±3.6)% after being incubated for 8 d. BMP/Gel/SH-Ag had obvious inhibitory effect on S. aureus and E. coli. CCK-8 results showed that BMP/Gel/SH-Ag had good biocompatibility. BMP/Gel/SH-Ag can increase the expression of ALP and the content of calcium nodules in rat BMSCs. Conclusion · The BMP/Gel/SH-Ag has good performance in promoting osteogenesis and anti-infection.

Key words: microfluidics, microsphere, bacteriostasis, injectable hydrogel, promoting osteogenesis

CLC Number: