Smart responsive hydrogel-based growth factor delivery systems: precise release and synergistic regeneration strategies for wound healing

Chronic wounds resulting from burns, infections, and/or diabetes represent a significant clinical challenge due to impaired healing processes, which can lead to severe complications and even amputation. Growth factors (GFs) play crucial roles in all stages of wound healing. However, their therapeutic efficacy is compromised by rapid proteolytic degradation within the wound microenvironment, while excessive concentrations can induce detrimental side effects. Hydrogels, with their three-dimensional network structure, serve as an ideal carrier for GF delivery, protecting bioactivity and enabling controlled release. This review first summarizes the key roles of different GFs in wound healing. It then focuses on hydrogel-based GF loading strategies (noncovalent and covalent binding) and the integration of stimuli-responsive mechanisms for on-demand spatiotemporal release. Additionally, the potential of synergistic therapy combining drugs or scaffold materials with hydrogel-GF systems is discussed. Finally, the application prospects of this technology in other regenerative fields are explored.