In situ gelation of PEG-PLGA-PEG hydrogels containing high loading of hydroxyapatite: in vitro and in vivo characteristics

Abstract

Thermosensitive hydrogels are renowned carriers that are used to deliver a variety of drugs with the aim of combating diseases. In this study, the injectability of thermosensitive hydrogels comprised of poly(ethylene glycol)-poly(lactic acid-co-glycolic acid)-poly(ethylene glycol) (PEG-PLGA-PEG, PELGE) and hydroxyapatite (HA) were examined for their ability to deliver bone morphological protein 2 (BMP-2). The physicochemical characteristics of PELGE, HA, and PELGE/HA hydrogel composites were investigated by 1H NMR, GPC, FTIR, XRD, SEM, and TEM. The rheological properties, injectability, in vitro degradation, and in vivo biocompatibility were investigated. The hydrogel with a weight ratio of 4:6 of polymer to HA was found to be resistant to auto-catalyzed degradation of acidic monomers (LA, GA) for a period of 70 days owing to the presence of alkaline HA. Injectability was quantitatively determined by the ejected weight of the hydrogel composite at room temperature and was a close match to the weight amount predetermined by the syringe pump. The results not only revealed that the PELGE/HA hydrogel composite presented a minor tissue response in the subcutis of ICR mice at eight weeks, but they also indicated an acceptable tolerance of the hydrogel composite in animals. Thus, PELGE/HA hydrogel composite is expected to be a promising injectable orthopedic substitute because of its desirable thermosensitivity and injectability.