Therapeutic strategies to enhance proliferation in diabetic wound contraction: a comprehensive review from 1991-2025.

The global rise in diabetes mellitus has been accompanied by a marked increase in associated complications, most notably impaired wound healing. Diabetic non-healing wounds arise from multifactorial pathophysiological mechanisms, including excessive and prolonged inflammation, immune dysregulation, impaired angiogenesis, defective fibroblast-to-myofibroblast transition and aberrant growth factor signaling. These abnormalities delay wound contraction and re-epithelialization, increasing susceptibility to infection, chronic ulceration and limb amputation. Traditional and complementary approaches such as herbal formulations, Ayurvedic practices, and natural bioactive compounds have demonstrated potential in mitigating oxidative stress, modulating inflammation and promoting neovascularization. In parallel, advanced technological interventions, including nanocomposite hydrogels, smart and responsive biomaterials, gene therapy and targeted growth factor delivery systems, are being developed to create a pro-regenerative wound microenvironment. Modern clinical strategies such as electromagnetic therapy, negative pressure wound therapy, electrospun nanofiber scaffolds and 3D/4D bioprinting further contribute to enhanced wound contraction and tissue regeneration. Additionally, bioengineered skin substitutes, stem cell-based therapies and innovative growth factor delivery platforms offer promising translational prospects. This review critically summarizes traditional, complementary, and innovative approaches reported up to 2025, with an emphasis on smart biomaterials, emerging therapies and relevant preclinical models, highlighting future directions for improving diabetic wound care and patient quality of life.