Original article (Basic research)

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

  • 刘立立1,崔文国1 ,
  • 2
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  • 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 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.

Cite this article

刘立立1,崔文国1 , 2 . Injectable hydrogel loaded with bone morphogenetic protein-2 microspheres for bacteriostasis and osteogenesis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2020 , 40(9) : 1184 -1192 . DOI: 10.3969/j.issn.1674-8115.2020.09.004

Outlines

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