Hyaluronic Acid Role in Biomaterials Prevascularization

Abstract Tissue vascularization is a major bottleneck in tissue engineering. In this review, the state of the art on the intricate role of hyaluronic acid (HA) in angiogenesis is explored. HA plays a twofold role in angiogenesis. First, when released as a free polymer in the extracellular matrix (ECM), HA acts as a signaling molecule triggering multiple cascades that foster smooth muscle cell differentiation, migration, and proliferation thereby contributing to vessel wall thickening. Simultaneously, HA bound to the plasma membrane in the pericellular space functions as a polymer block, participating in vessel formation. Starting with the HA origins in native vascular tissues, the approaches aimed at achieving vascularization in vivo are reviewed. The significance of HA molecular weight (MW) in angiogenesis and the challenges associated with utilizing HA in vascular tissue engineering (VTE) are conscientiously addressed. The review finally focuses on a thorough examination and comparison of the diverse strategies adopted to harness the benefits of HA in the vascularization of bioengineered materials. By providing a nuanced perspective on the multifaceted role of HA in angiogenesis, this review contributes to the ongoing discourse in tissue engineering and advances the collective understanding of optimizing vascularization processes assisted by functional biomaterials.