Advancing vascularization with VEGF-bound hydrogels in tissue engineering

Tissue vascularization continues to be a significant and unresolved challenge in in vitro tissue engineering. A promising approach involves binding vascular endothelial growth factor (VEGF) to engineered hydrogels, which stimulates endothelial cells (ECs) to form functional blood vessels. VEGF plays a central role in vascular development from embryogenesis to adulthood by promoting new blood vessel formation and regulating EC proliferation, migration, survival, differentiation, and vascular remodeling. However, vascularization outcomes depend not only on the presence of VEGF but also on its retention, release, and temporal availability to ECs, relationships that remain insufficiently clarified in current VEGF-bound hydrogel studies. Here, we provide a systematic overview of VEGF-bound hydrogels for tissue vascularization, covering major VEGF family members, VEGF-binding strategies within hydrogels, and representative tissue-engineering applications. In particular, VEGF-bound hydrogels are discussed according to the binding strength, including weakly bound, moderately bound, strongly bound, and dynamic or stimulus-responsive systems. We further summarize their applications in cardiovascular tissue engineering, bone regeneration, wound healing, neural repair, and engineered vascular network models. Collectively, this review highlights recent advances in VEGF-bound hydrogels and provides insights for future improvements in constructing physiological models for clinical translation.