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

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.

Synthesis of Chitosan/Diatomite Composite as an Advanced Delivery System for Ibuprofen Drug; Equilibrium Studies and the Release Profile

“…Interested researchers have developed several methods to enhance the stability; bio-distribution, solubility, and selectivity of the IB drug in addition to the role of such techniques in controlling the released dosages of the drug, improving the patient compliance, and inducing its therapeutic efficiency. − Introducing the drug at gradual delivery, managed dose, aggressively pursued, and targeted delivery using innovative carriers were recommended as promising methods to avoid all of the reported side effects. ,, The studied carriers for the IB drug involved mesoporous silica, hydroxyapatite, montmorillonite, titanium alloy, and MOFs. ,, …”

Polyurethane‐basedcomposites with promising antibacterial properties

“…Kuang et al 183 reported a dual-function PU scaffold with nano-hydroxyapatite (n-HAp) and mesoporous silica nanoparticles (MSNs). The resultant composite was loaded with levofloxacin and used to treat osteomyelitis and bacterial infections.…”

Bioceramic-based scaffolds with antibacterial function for bone tissue engineering: A review

“… Drugs loaded in scaffolds Antibacterial mechanisms Bacterial species Ref. Tetracyclines PCL/MBG Doxycycline Inhibiting synthesis of protein S. aureus , E. coil, S. epidermidis, P. aeruginosa , [ 32 , 39 ] Gelatin/HA Tetracycline S. aureus [ 40 ] β-lactams CS/calcium phosphate cements; Penicillin Inhibiting synthesis of cell walls S. aureus [ 41 ] Agarose/nano hydroxycarbonateapatite Cephalexin [ 42 ] Aminoglycosides TiO 2 scaffold; Poly (glycidyl methacrylate)/hydroxyapatite Gentamicin Inhibiting synthesis of protein S. aureus , S. epidermidis, E. coli [ 25 , 43 , 44 ] Quinolones Polyurethane/silica/nano-hydroxyapatite Levofloxacin Inhibiting synthesis or function of nucleic acid S. aureus , E. coli [ 45 ] Monticellite Ciprofloxacin [ 46 ] Glycopeptides Baghdadite (Ca 3 ZrSi 2 O 9 ) Vancomycin Inhibiting synthesis of cell wall S. aureus [ ...…”

“…Quinolones drugs represented by levofloxacin and ciprofloxacin are also widely used in the treatment of bone implant-associated infection due to their ability to penetrate into trabecular and cortical bone and thus minimize the risk of resistance selection [ 45 , 46 ]. For example, a novel polyurethane/mesoporous silica/nano-hydroxyapatite scaffold containing levofloxacin was developed by a foaming method [ 45 ]. The sustained release behavior of levofloxacin was significantly increased by encapsulating it in mesoporous silica nanoparticles.…”