This research addresses the urgent public health issue of osteoporosis-related bone fractures, occurring every 3 seconds worldwide, imposing substantial morbidity, mortality, and healthcare costs. Current therapeutics face limitations in efficacy and side effects, necessitating innovative approaches. Physical loading has emerged as a potent regulator of bone formation, with recent findings indicating that bone cells release multifunctional paracrine factors via extracellular vesicles (EVs). Leveraging prior work on scaffolds for accelerated bone regeneration, this project focuses on functionalizing hydrogels with bone cell-derived EVs to expedite clinical translation for bone repair.
The hypothesis posits that incorporating bone cell-derived EVs into a collagen-alginate hydrogel system enables controlled delivery for bone repair. Objective 1 involves determining the impact of varying alginate and collagen concentrations on EV binding efficiency and hydrogel properties. Advanced crosslinking methodologies, including the competitive ligand exchange crosslinking ion method, will be employed, with EV labelling and confocal microscopy for characterization.
Objective 2 aims to evaluate EV release kinetics from hydrogel systems. A computer-aided design insert simulating the bone defect site will be 3D-printed, followed by a 2-week release study and flow-cytometry-based quantification of released EVs. The outcomes will identify key parameters for sustained EV release, enhancing continuous bioavailability at the bone defect site. Overall, this research bridges a critical gap in osteoporosis treatment, offering a promising avenue for advanced therapeutic interventions in bone repair.