Transglutaminase Cross-Linked Gelatin-Alginate-Antibacterial Hydrogel as the Drug Delivery-Coatings for Implant-Related Infections

Abstract

Implant-related infection may be catastrophic and result in poor functional outcome, chronic osteomyelitis, implant failure or even sepsis and death. Based on a transglutaminase (TGase) cross-linked/antibiotics-encapsulated gelatin-alginate hydrogel, the main aim of this study is to establish an effective antibiotic slow-release system. The second aim is to evaluate the efficacy of a hydrogel-encapsulated antibiotic-containing titanium pin in preventing implant-related infections in a rat model. The prepared gelatin/alginate/gentamicin or vancomycin hydrogel was covalently cross-linked with transglutaminase (TGase). Its drug release profile and cytotoxicity were determined and the Wistar rat animal model was performed to validate its efficacy by radiographic examination, Micro-CT (computed tomography) evaluation and histo-morphological analysis at 12 weeks after surgery. When gelatin and alginate were thoroughly mixed with TGase, both 0.5% and 1.0% TGase can effectively cross link the hydrogel; the release of antibiotic is slowed down with higher degree of TGase concentration (from 20 min to more than 120 h). In the animal study, antibiotic-impregnated hydrogel is effective in alleviating the implant-related infections. Relative to that of a positive control group, the experimental group (vancomycin treatment group) showed significant higher bone volume, more intact bony structure with only mild inflammatory cell infiltration. This newly designed hydrogel can effectively deliver antibiotics to reduce bacterial colonization and biofilm formation on the implant surface. The remaining challenges will be to confer different potent antibacterial medications with good biocompatibility and fulfill the safety, practical and economic criteria for future clinical translation.

Advances in Nanostructures for Antimicrobial Therapy

“…Efficient delivery of VAN with a subsequent reduction of bacterial colonization and biofilm formation on the implant surface was reported also for transglutaminase cross-linked gelatin-ALG hydrogel encapsulating this antibiotic. This formulation effectively mitigated the implant-related infections in an animal study, which was reflected in a considerably increased bone volume and a more intact bony structure showing only slight inflammatory cell infiltration compared to control [ 220 ]. By ionotropic gelation fabricated ALG with poly-L-lysine, which was conjugated with CIP, nanogels were fabricated.…”

Transglutaminase-Catalyzed Bottom-Up Synthesis of Polymer Hydrogel

“…Gelatin hydrogel encapsulated human adipocyte globules can increase the cell proliferation significantly with low cytotoxicity ( Tsai et al, 2020 ). A sustained-release absorbable hydrogel by combining TGase with gelatin, alginate and antibiotics has developed for local delivery of antibiotics in orthopedic surgery ( Sun et al, 2021 ). Gupta et al (2021) used gelatin hydrogel prepared by MTGase crosslinking as an engineered skeletal muscle matrix, and the hydrogel was stable after 2 weeks under similar culture conditions of natural skeletal muscle.…”

Recent Advances in Functional Polymer Materials for Energy, Water, and Biomedical Applications: A Review

“…Currently, functional polymers and are experiencing a rapid and continuous progress as drug delivery and protein purification systems. Due to their diversity, surface and bulk properties, polymers are the most effective biomaterials applied in drug formulations and in drug delivery devices such as implants [133][134][135]. Recent drug delivery systems involve dendrimers, micelles, polymeric nanoparticles, liposomes, microcapsules, cell ghosts, and lipoproteins.…”