Angiogenesis: A Key to Advancing Urethral Engineering.

Urethral stricture is a common urological condition in men that significantly affects quality of life. Autografts remain the gold standard for substitution urethroplasty; however, they present unavoidable limitations that tissue engineering seeks to overcome. One of the main challenges in long-segment urethral strictures is achieving an effective graft capable of providing adequate oxygen and nutrient delivery, thereby preventing graft necrosis and failure. Therefore, both angiogenesis induction and mechanical integrity of the grafts are critical for successful urethroplasty. This review provides an integrated framework encompassing three complementary strategies for promoting angiogenesis in urethral tissue engineering: (i) angiogenesis guided substrates, (ii) growth factor delivery systems, and (iii) cell-based therapies. Unlike previous reviews that focus on isolated aspects, our work provides a comprehensive and comparative discussion of these approaches within the specific context of urethroplasty. In addition, we highlight the translational challenges and pitfalls associated with each strategy, underscoring the need for standardized scaffold design, optimized cell culture protocols, and rigorous clinical validation. Despite ongoing progress, no optimal graft has yet been developed to ensure adequate vascularization for long segment urethral defects. Nevertheless, current findings suggest that angiogenesis induction holds promising potential for advancing urethral tissue engineering and improving clinical outcomes.