Integrative Biomedical Research
Integrative Biomedical Research (Journal of Angiotherapy) | Online ISSN 3068-6326
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Volume 10 Number 1 2026
RESEARCH ARTICLE (Open Access)
Therapeutic Angiogenesis: From Single-Factor Failures to Precision Vascular Regeneration
Habeeb Akorede Lawal 1,2, Aisha Eniola Olayiwola 1,3*, Abdulquadir Abdulhafeez 4, Adedolapo Aishat Bakare 5, Nimatallahi Olamide Tajudeen 6, Ibrahim Ahmed Bashir 2,7, Zainab Ajoke Suleiman 1,8, Wahab Muiz 9, Abdulrahman Olamilekan Raji 1,8, Abdulmajeed Opeyemi Agboola 6, Olalekan John Okesanya 10,11, Olalere Oluwaseun Olaniyi 12, Tolutope Adebimpe Oso 10,13
Integrative Biomedical Research 10 (1) 1-26 https://doi.org/10.25163/biomedical.10110794
Submitted: 28 April 2026 Revised: 30 June 2026 Accepted: 07 July 2026 Published: 09 July 2026
Abstract
Ischemic vascular diseases, including peripheral artery disease, chronic limb-threatening ischemia, ischemic heart disease, diabetic ulcers, and stroke, remain major causes of morbidity, mortality, disability, and healthcare expenditure worldwide. Despite significant advances in surgical and endovascular revascularization, a substantial proportion of patients remain unsuitable for conventional interventions, creating an urgent need for regenerative strategies capable of restoring tissue perfusion and promoting functional repair. Therapeutic angiogenesis, the controlled induction of new blood vessel formation, has emerged as a promising approach for addressing this unmet clinical need. However, early angiogenic therapies based primarily on single growth-factor delivery produced inconsistent clinical outcomes, highlighting the complexity of vascular regeneration and the limitations of reductionist therapeutic designs. This review critically examines the biological foundations, historical evolution, translational progress, and public health relevance of therapeutic angiogenesis. Particular emphasis is placed on recent advances in gene-based therapies, stem and progenitor cell approaches, engineered extracellular vesicles, biomaterial-assisted delivery systems, hypoxia-responsive platforms, and metabolic and immune regulatory mechanisms that collectively shape angiogenic responses. We further discuss disease-specific applications in chronic limb-threatening ischemia, diabetic wound healing, myocardial repair, bone regeneration, and other ischemic disorders, while highlighting contexts in which angiogenic stimulation may be detrimental, such as retinal neovascular diseases. Emerging evidence indicates that successful vascular regeneration requires coordinated modulation of endothelial signaling, immune responses, extracellular matrix remodeling, metabolic adaptation, and vessel maturation rather than isolated stimulation of endothelial proliferation. Finally, we evaluate key translational challenges, including safety concerns, delivery efficiency, manufacturing scalability, patient stratification, regulatory considerations, and implementation in resource-limited settings. Collectively, current evidence suggests that next-generation, multimodal, and precision-guided angiogenic therapies may overcome historical barriers and enable clinically meaningful vascular regeneration, positioning therapeutic angiogenesis as an increasingly important component of future regenerative medicine and public health strategies.
Keywords: Chronic limb-threatening ischemia; extracellular vesicles; ischemic disease; peripheral artery disease; therapeutic angiogenesis.
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