Peptide Hydrogel for Sustained Release of Recombinant Human Bone Morphogenetic Protein-2 In Vitro.

Abstract

This study aimed to investigate the impact of varying the formulation of a specific peptide hydrogel (PepGel) on the release kinetics of rhBMP-2 in vitro. Three PepGel formulations were assessed: (1) 50% <i>v</i>/<i>v</i> (peptides volume/total volume) PepGel, where synthetic peptides were mixed with crosslinking reagents and rhBMP-2 solution; (2) 67% <i>v</i>/<i>v</i> PepGel; (3) 80% <i>v</i>/<i>v</i> PepGel. Each sample was loaded with 12 µg of rhBMP-2 and incubated in PBS. Released rhBMP-2 was quantified by ELISA at 1 h, 6 h, and 1, 2, 4, 7, 10, 14, and 21 days. To explore how PepGel formulations influence rhBMP-2 release, the gel porosities, swelling ratios, and mechanical properties of the three PepGel formulations were quantitatively analyzed. The results showed that rhBMP-2 encapsulated with 50% <i>v</i>/<i>v</i> PepGel exhibited a sustained release over the 21-day experiment, while the 67% and 80% <i>v</i>/<i>v</i> PepGels demonstrated significantly lower rhBMP-2 release rates compared to the 50% formulation after day 7. Higher histological porosity of PepGel was significantly correlated with increased rhBMP-2 release rates. Conversely, the swelling ratio and elastic modulus of the 50% <i>v</i>/<i>v</i> PepGel were significantly lower than that of the 67% and 80% <i>v</i>/<i>v</i> formulations. In conclusion, this study indicates that varying the formulation of crosslinked PepGel can control rhBMP-2 release rates in vitro by modulating gel porosity, swelling ratio, and mechanical properties. Encapsulation with 50% <i>v</i>/<i>v</i> PepGel offers a sustained rhBMP-2 release pattern in vitro; if replicated in vivo, this could mitigate the adverse effects associated with burst release of rhBMP-2 in clinical applications.