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% v/v (peptides volume/total volume) PepGel, where synthetic peptides were mixed with crosslinking reagents and rhBMP-2 solution; (2) 67% v/v PepGel; (3) 80% v/v 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% v/v PepGel exhibited a sustained release over the 21-day experiment, while the 67% and 80% v/v 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% v/v PepGel were significantly lower than that of the 67% and 80% v/v 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% v/v 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.

The widespread clinical application of collagen sponge-delivered recombinant human bone morphogenetic protein-2 (rhBMP-2) for spinal fusion currently remains limited. This limitation is due to potential adverse events associated with the rapid release of excessively high doses. This study aimed to investigate the impact of varying PGmatrix 3D Shape peptide hydrogel (PepGel) formulations on the release kinetics of rhBMP-2 in vitro. Three PepGel formulations were assessed: 1) 50% v/v PepGel, where solution A (crosslinking reagent) was mixed with solution B (synthetic peptides) and rhBMP-2 solution, making a 50% v/v (solution B volume/total volume) PepGel; 2) 67% v/v PepGel; 3) 80% v/v PepGel. Each sample was loaded with 12 µg of rhBMP-2 and incubated in PBS. The incubation solution containing released rhBMP-2 was collected at 1 hour, 6 hours, and 1, 2, 4, 7, 10, 14, and 21 days, and released rhBMP-2 was quantified using a BMP-2 ELISA kit. 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% v/v PepGel exhibited a sustained release over the 21-day experiment. Between days 7 and 21, the 50% v/v PepGel demonstrated significantly higher rhBMP-2 release rates compared to the 67% and 80% v/v formulations. Higher histological porosity of PepGel was significantly correlated with increased rhBMP-2 release rates. Conversely, the swelling ratio and elastic modulus at 1.0 Hz of the 50% v/v PepGel was significantly lower than that of the 67% and 80% v/v 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% v/v PepGel offers a sustained rhBMP-2 release pattern, which could mitigate the adverse effects associated with burst release of rhBMP-2 if replicated in vivo.

Osteoarthritis (OA) is the most prevalent joint disease, which is pathologically characterized by articular cartilage degradation, chronic synovial inflammation, subchondral bone remodeling, and osteophyte formation. Patients with OA suffer from joint pain, deformity, and functional impairment. Current therapies provide symptomatic relief but fail to halt or reverse disease progression. Gene therapy is being investigated for cartilage repair and modulation of intra-articular inflammation, with the aim of modifying disease progression. This narrative review summarizes the recent advances in viral and non-viral gene therapy approaches for OA, including therapeutic gene targets in preclinical and clinical trials. Potentially therapeutic genes can be injected into the joint cavity and transferred into specific joint tissue cells through viral vectors or non-viral carriers depending on the nature of transgenes, delivery materials, and targeting cells. Gene delivery to articular chondrocytes remains challenging as the cells are positioned in a dense extracellular matrix, while synovial fluid may further contribute to degradation or inactivation of delivered agents. Viral vectors, particularly adeno-associated virus (AAV), can support sustained transgene expression in joint tissues, although cartilage penetration efficiency remains to be improved. Non-viral carriers can deliver nucleic acids to synovial cells and, with suitable formulations, articular chondrocytes. Viral and non-viral delivery approaches may offer complementary benefits; integrating the advantages of both viral and non-viral platforms could potentially improve the efficacy and safety of gene therapy for OA. Finally, strategies to overcome translational barriers and future directions towards clinical applications are discussed.