Preparation Of PLGA-PEG-PLGA Thermosensitive Hydrogels For Orthopaedic Application

Osteomyelitis and tendon adhesion formed after surgery have alwaysbeen problems for the clinical workers. Local application of drugs canachieve good clinical outcome. So looking for an effectively drug releasesystem has always been an objective for the researcher. Over the past twodecades, polymeric hydrogels have received more and more attention tobe applied in the biomedical field. Thermosensitive hydrogels havereceived considerable attention recently due to simple operation, nointroduction of organic solvent and high safety, which can embedpeptides, proteins, cells and drugs. In recent years, the FDA has approvedpolymers such as poly lactide (PLA), poly lactic-co-glycolic acid (PLGA)to use in clinical trials, hence PLGA-PEG-PLGA thermosensitivehydrogels have received considerable attention for the researchers. In thisstudy, we prepared a series of PLGA-PEG-PLGA polymers and animalexperiments were carried out.1) PLGA-PEG-PLGA polymers were prepared by ring openingpolymerization. The vancomycin loaded hydrogels showed a sol-gel-precipitation phase transition with increasing temperature, and thehydrogels displayed the maximum storage moduli at around physiologicaltemperature. Vancomycin can steadily release from hydrogels and hasgood antibacterial effect. Degradation in vivo and in vitro and cellexperiments show that the triblock copolymers have good biodegradable.In vivo antibacterial experiment shows vancomycin co loaded PLGA- PEG-PLGA hydrogels can treatment osteomyelitis effectively and thereis no associated side effect of the drug.2) According to the problem of bone repair, we designed a kind ofPLGA-PEG-PLGA/HA composite gel. Rheology, sol-gel phase transitionand CMC showed that PLGA-PEG-PLGA/HA composite gel can stillexhibited sol-gel phase transition and the storage modulus of thehydrogels was enhanced. FT-IR, XRD and TEM showed that thehydroxyapatite can dispersed in the PLGA-PEG-PLGA uniformly.Furthermore, the acidic pH environment of the hydrogel which wasneutralized by HA brought a better biocompatibility in vitro. In vivoantibacterial experiments, the composite not only showed goodantibacterial property, but also exhibited more excellent characteristics ofbone repair.3) Finally, we designed a kind of5-Fu-loaded PLGA-PEG-PLGAhydrogels. The sustained release of5-Fu from the hydrogels lasted over7days. The PLGA-PEG-PLGA hydrogels degraded within4weeks aftersubcutaneous injection into rats, and showed acceptable biocompatibilityin vivo. The anti-adhesion efficacy of the hydrogels with or without5-Fuduring the Achilles tendon healing of rats was evaluated by macroscopicevaluation and histological analysis. It was found that the group treatedwith5-Fu-loaded hydrogels showed a significant inhibition of adhesionformation when compared to the untreated group or the group treatedwith the hydrogels only.