Advancements in Promoting Angiogenesis in Tissue-Engineered Grafts in Various Organs: A Comprehensive Review

Abstract

Vascularization remains a fundamental challenge in tissue engineering, directly impacting the survival, integration, and function of engineered grafts across diverse organ systems. This comprehensive review explores the latest advancements in promoting angiogenesis within tissue-engineered constructs, focusing on strategies that emulate natural vascular development to overcome ischemic limitations post-implantation. We examine three core domains of pro-angiogenic intervention: controlled delivery of growth factors (e.g., VEGF, FGF, PDGF), development of bioactive and mechanically tuned biomaterials (such as collagen, gelatin, hyaluronic acid, and decellularized matrices), and cell-based approaches leveraging stem and progenitor cells, including embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells. Novel technologies such as 3D bioprinting, nanofabrication, and the use of extracellular vesicles have further enabled spatial and temporal control over vascular network formation. Organ-specific applications in cardiac, hepatic, dermal, osseous, pancreatic, musculoskeletal, adipose, and corneal tissues illustrate the translational potential of these techniques, while also highlighting the unique vascular requirements of each tissue type. Additionally, unconventional angiogenic inducers, such as parasite-derived proteins, are emerging as potential therapeutic tools. Despite significant progress, challenges remain in achieving long-term vessel stability, synchronizing vascularization with lymphangiogenesis and immunomodulation, and navigating regulatory complexities for clinical implementation. This review underscores the centrality of angiogenesis in regenerative medicine and advocates for continued interdisciplinary efforts to refine vascular integration strategies that will enable durable, functional, and patient-specific tissue replacements.