Abstract
Chronic wounds pose a persistent clinical and economic burden, often failing to respond to standard care as a result of impaired angiogenesis, prolonged inflammation, and dysfunctional cellular activity. Emerging strategies in regenerative medicine offer new hope, particularly those focusing on stem cell therapy, growth factor modulation, and mechanical support. This narrative emphasizes the clinical applicability. We performed targeted searches of PubMed/MEDLINE and Embase using terms related to regenerative cell therapy, growth factor modulation, mechanical/physical strategies, adjuvant therapies, and platelet-derived products (PRP/PRF). We prioritized randomized/controlled studies, high-quality observational cohorts, meta-analyses, and consensus guidelines relevant to chronic wound healing, and we critically appraised heterogeneity and limitations. In particular, the latest innovations in chronic wound management, mesenchymal stem cells (MSCs), and adipose-derived stem cells (ASCs) have shown promise in promoting angiogenesis and modulating immune responses. Concurrently, the targeted delivery of cytokines such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and epidermal growth factor (EGF) is being optimized through advanced biomaterials to enhance healing microenvironments. Mechanical interventions, including negative pressure wound therapy (NPWT) and shock wave therapy, further support tissue repair and revascularization. Together, these approaches reflect a shift from symptomatic wound care to personalized, regenerative strategies. This review synthesizes preclinical and clinical data, explores translational challenges, and outlines future directions that integrate biology, bioengineering, and digital tools for optimized wound healing.