Antibacterial and Osteogenic Doxycycline Imprinted Bioglass Microspheres to Combat Bone Infection

Currently, postoperative infection is a significant challenge in bone and dental surgical procedures, demanding the exploration of innovative approaches due to the prevalence of antibiotic-resistant bacteria. This study aims to develop a strategy for controlled and smart antibiotic release while accelerating osteogenesis to expedite bone healing. In this regard, temperature-responsive doxycycline (DOX) imprinted bioglass microspheres (BGMs) were synthesized. Following the formation of chitosan-modified BGMs, poly N-isopropylacrylamide (pNIPAm) was used for surface imprinting of DOX. The temperature-responsive molecularly imprinted polymers (MIPs) exhibited pH and temperature dual-responsive adsorption and controlled-release properties for DOX. The temperature-responsive MIP was optimized by investigating the molar ratio of N,N'-methylene bis(acrylamide) (MBA, the cross-linker) to NIPAm. Our results demonstrated that the MIPs showed superior adsorption capacity (96.85 mg/g at 35 °C, pH = 7) than nonimprinted polymers (NIPs) and manifested a favorable selectivity toward DOX. The adsorption behavior of DOX on the MIPs fit well with the Langmuir model and the pseudo-second-order kinetic model. Drug release studies demonstrated a controlled release of DOX due to imprinted cavities, which were fitted with the Korsmeyer-Peppas kinetic model. DOX-imprinted BGMs also revealed comparable antibacterial effects against Staphylococcus aureus and Escherichia coli to the DOX (control). In addition, MIPs promoted viability and osteogenic differentiation of MG63 osteoblast-like cells. Overall, the findings demonstrate the significant potential of DOX-imprinted BGMs for use in bone defects. Nonetheless, further in vitro investigations and subsequent in vivo experiments are warranted to advance this research.