The clinical application of growth factors (GFs) is often hindered by their low stability in physiological environments. Using biomaterial vehicles for controlled GF delivery offers protection from proteases, targeted delivery, and sustained release. However, existing methods for incorporating GFs into biomaterials have limitations. Direct adsorption and encapsulation lead to burst release, while covalent incorporation allows for a customisable release profile but involves more complex processes and chemical modification of GFs. Bioaffinity methods provide long-term release but lack specificity, making them dependent on the type of GF used. This study introduces tyraminated poly-vinyl-alcohol (PVA-Tyr) as a GF delivery vehicle capable of covalently incorporating native GFs through a photo-initiated cross-linking process that forms biphenol bonds. Mass loss and release studies showed that protein-loaded PVA-Tyr hydrogels had adjustable degradation times ranging from 7 to 92 days, during which the covalently incorporated proteins were released linearly. Incorporating bovine serum albumin (BSA), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), or brain-derived growth factor (BDNF) resulted in similar incorporation efficiencies and release profiles, highlighting the system's low specificity and versatility. Additionally, functional studies indicated that VEGF, bFGF, and BDNF released from PVA-Tyr hydrogels could enhance the metabolic activity, migration, and 3D vessel formation of endothelial cells and mesenchymal stem cells. The PVA-Tyr hydrogels were further validated in a range of small and large animal models, all showing positive effect specific to the targeted applications – vascular infiltration in subcutaneous mouse model, acute rotator cuff repair in sheep models and avascular necrosis in pig model. Overall, PVA-Tyr exhibits high potential as a customisable GF delivery tool for various regenerative medicine applications.

Khoon Lim

Associate Professor and ARC Future Fellow

University of Sydney

2025 Programme