Osteogenic and antibacterial dual functions of a novel levofloxacin loaded mesoporous silica microspheres/nano-hydroxyapatite/polyurethane composite scaffold

Zhiping Kuang; Guangming Dai; Ruijie Wan; Dongli Zhang; Chen Zhao; Cheng Chen; Jidong Li; Hongchen Gu; Wei Huang

doi:10.1016/j.gendis.2019.09.014

Osteogenic and antibacterial dual functions of a novel levofloxacin loaded mesoporous silica microspheres/nano-hydroxyapatite/polyurethane composite scaffold

Genes Dis. 2019 Oct 5;8(2):193-202. doi: 10.1016/j.gendis.2019.09.014. eCollection 2021 Mar.

Authors

Zhiping Kuang^{1

2}, Guangming Dai¹, Ruijie Wan^{1

2}, Dongli Zhang¹, Chen Zhao¹, Cheng Chen¹, Jidong Li³, Hongchen Gu⁴, Wei Huang¹

Affiliations

¹ Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China.
² Department of Orthopaedic Surgery, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400011, PR China.
³ Research Center for Nano-Biomaterials, Analytical & Testing Center, Sichuan University, Chengdu, Sichuan Province, 610065, PR China.
⁴ State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiaotong University, Shanghai, 200240, PR China.

Abstract

Lev/MSNs/n-HA/PU has been proved to be a novel scaffold material to treat bone defect caused by chronic osteomyelitis. We have previously identified that this material can effectively treat chronic osteomyelitis caused by Staphylococcus aureus in vivo. However, the potential mechanisms of antibacterial and osteogenic induction properties remain unclear. Thus, for osteogenesis property, immunohistochemistry, PCR, and Western blot were performed to detect the expression of osteogenic markers. Furthermore, flow cytometry and TUNEL were applied to analyze MC3T3-E1 proliferation and apoptosis. For antibacterial property, the material was co-cultivated with bacteria, bacterial colony forming units was counted and the release time of the effective levofloxacin was assayed by agar disc-diffusion test. Moreover, scanning electron microscope was applied to observe adhesion of bacteria. In terms of osteogenic induction, we found BMSCs adherently grew more prominently on Lev/MSNs/n-HA/PU. Lev/MSNs/n-HA/PU also enhanced the expression of osteogenic markers including OCN and COL1α1, as well as effectively promoted the transition from G1 phase to G2 phase. Furthermore, Lev/MSNs/n-HA/PU could reduce apoptosis of MC3T3-E1. Besides, both Lev/MSNs/n-HA/PU and n-HA/PU materials could inhibit bacterial colonies, while Lev/MSNs/n-HA/PU possessed a stronger antibacterial activities, and lower bacterial adhesion than n-HA/PU. These results illustrated that Lev/MSNs/n-HA/PU composite scaffold possess favorable compatibility in vitro, which induce osteogenic differentiation of MSCs, promote proliferation and differentiation of MC3T3-E1, and inhibit apoptosis. Moreover, clear in vitro antibacterial effect of Lev/MSNs/n-HA/PU was also observed. In summary, this study replenishes the potential of Lev/MSNs/n-HA/PU composite scaffold possess dual functions of anti-infection and enhanced osteogenesis for future clinical application.

Keywords: Antibacterial; Composite scaffold; Levofloxacin; Nanobiomaterial; Osteogenesis.