Antibacterial and osteogenic activities of clindamycin-releasing mesoporous silica/carboxymethyl chitosan composite hydrogels

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.

Biodegradable Dual-Function Nanocomposite Hydrogels for Prevention of Bisphosphonate-Related Osteonecrosis of the Jaw

“…In this study, CDM was used as a water-soluble (hydrophilic) model drug to be loaded into PMCM-41, while GGOH was used as a poorly water-soluble (less hydrophillic) model drug to be loaded into NMCM-41. The loading of each drug into each nanocarrier was carried out according to the previously reported adsorption method . The brief procedures are as follows.…”

“…The combinations of polymeric biomaterials and MSNs for drug delivery applications have attracted great attention. − Recently, we have successfully developed the CDM-loaded composite hydrogels consisting of biodegradable CMCS and CDM-loaded unmodified or plasma-treated MCM-41 nanoparticles . The composite hydrogels with prolonged release profiles of up to 10 days effectively inhibited the growth of Streptococcus sanguinis for at least 14 days in vitro .…”

Mesoporous Materials Make Hydrogels More Powerful in Biomedicine

“…The introduction of antibacterial drugs [ 97 , 123 , 124 , 125 ], antimicrobial peptides [ 126 ], or other antibacterial substances into the three-dimensional network structure of hydrogels through mesoporous materials is one of the most proven and effective methods to enhance the antibacterial and anti-inflammatory effect of hydrogels. Mesoporous materials loaded with antibacterial substances display overwhelming anti-inflammatory and antibacterial effectiveness with longer time and smaller doses [ 127 ].…”

Implantable biomedical materials for treatment of bone infection

“…Studies have shown that the prepared scaffold has good biocompatibility, a large specific surface area, and is endowed with the antibacterial activity of Cu, which has excellent bactericidal activity against Gram-positive bacteria. Biodegradable composite hydrogels composed of carboxymethyl chitosan and clindamycin-loaded mesoporous silica nanoparticles possess multiple antibacterial activities and induce osteogenesis by modulating alkaline phosphatase activity ( Sungkhaphan et al, 2021 ).…”