Abstract
Conventional treatment of jaw bone infection is often ineffective at controlling bacterial infection and enhancing bone regeneration. Biodegradable composite hydrogels comprised of carboxymethyl chitosan (CMCS) and clindamycin (CDM)-loaded mesoporous silica nanoparticles (MCM-41), possessing dual antibacterial activity and osteogenic potency, were developed in the present study. CDM was successfully loaded into both untreated and plasma-treated MCM-41 nanoparticles, denoted as (p)-MCM-41, followed by the incorporation of each of CDM-loaded (p)-MCM-41 into CMCS. The resulting CDM-loaded composite hydrogels, (p)-MCM-41-CDM-CMCS, demonstrated slow degradation rates (about 70% remaining weight after 14-day immersion), while the CDM-free composite hydrogel entirely disintegrated after 4-day immersion. The plasma treatment was found to improve drug loading capacity and slow down initial drug burst effect. The prolonged releases of CDM from both (p)-MCM-41-CDM-CMCS retained their antibacterial effect against Streptococcus sanguinis for at least 14 days in vitro. In vitro assessment of osteogenic activity showed that the CDM-incorporated composite hydrogel was cytocompatible to human mesenchymal stem cells (hMSCs) and induced hMSC mineralization via p38-dependent upregulated alkaline phosphatase activity. In conclusion, novel (p)-MCM-41-CDM-CMCS hydrogels with combined controlled release of CDM and osteogenic potency were successfully developed for the first time, suggesting their potential clinical benefit for treatment of intraoral bone infection.
Highlights
Jaw bone infection, such as osteomyelitis, infected osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ), has been a major challenge in public healthcare with serious social and economic implications
The results suggest that the p-Mobil Composition of Matter N0.41 (MCM-41)-200CDM-carboxymethyl chitosan (CMCS) composite hydrogel might induce human mesenchymal stem cells (hMSCs)-mediated mineralization via p38-dependent upregulated ALP activity
The levels of CDM released from the composite hydrogels after day 10 might be too low to be detected by high performance liquid chromatography (HPLC)
Summary
Jaw bone infection, such as osteomyelitis, infected osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ), has been a major challenge in public healthcare with serious social and economic implications. Treatment of jaw bone infection is complicated by persistent exposure to oral bacteria and insufficient vascularization. The most commonly reported microorganisms are obligate or facultative anaerobic species, such as viridans streptococci and staphylococci [1]. Surgical treatment with prolonged (weeks to months) antibiotic therapy is normally required [1]. Bacterial infection is noted to have some role in the development of MRONJ [2]. Bone infection is often associated with abnormal bone remodelling due to a defective bone repair process at the infection site. Conventional treatment is frequently ineffective at controlling the infection and enhancing bone regeneration, with an alternative approach being required
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