Diabetes and Wound Healing: Pathophysiology, Complications, and Emerging Therapies

Naeem Hamza^1*, Krish Shah¹ , Yasmin Schukur¹ , Diana Roibu¹ , Naeema Zainaba¹ and Felix Nandor Richard Bragg¹

Abstract

Diabetic wound healing represents a paradigm of therapeutic recalcitrance, wherein hyperglycaemia disrupts the orchestrated progression of hemostasis, inflammation, proliferation, and remodeling phases, culminating in chronic ulceration and amputation risk. This narrative review synthesizes pathophysiological mechanisms underpinning these deficits, emphasizing protracted inflammation via M1 macrophage dominance and cytokine surfeit (TNF-α, IL-6, IL1β), oxidative/nitrosative disequilibria from mitochondrial superoxide excess and polyol/AGE/hexosamine fluxes, and cellular impairments in fibroblasts (senescence, migratory arrest), keratinocytes (re-epithelialization failure), and endothelial cells (angiogenic paucity). Vascular sequelae—microvascular (retinopathy, nephropathy, neuropathy with 60–85% ulcer attribution) and macrovascular (atherothrombosis)—exacerbate hypoxia via HIF-1α proteasomal sabotage, while motor neuropathy fosters deformities and gait derangements amplifying plantar shear. Emergent factors include biofilm-mediated persistence (68–77% DFU prevalence), MMP/TIMP imbalance eroding ECM integrity, and epigenetic "metabolic memory" via histone/DNA modifications and non-coding RNAs sustaining M1 skew and angiogenic suppression. Multifactorial interventions—glycaemic intensification (HbA1c <7%), protease modulation, biofilm disruption, and epigenetic editors—yield 25–76% risk attenuation across trials, yet gaps in longitudinal epigenomic profiling and personalized CRISPR therapeutics persist. Bridging these informs precision strategies to restore redox homeostasis, phenotypic plasticity, and vascular dynamism, mitigating the $15–30 billion annual DFU burden.

Keywords

Diabetes, Wound healing, Pathophysiology, CRISPR, DFU, Macrophages

Corresponding Author

Naeem Hamza, Iuliu Hatieganu University of medicine and pharmacy cluj Napoca, Romania.

Citation

Hamza, N., Shah, K., Schukur, Y., Roibu, D., Zainaba, N., et.al. (2025). Diabetes and Wound Healing: Pathophysiology, Complications, and Emerging Therapies. Med Pharmacol Open Access. 1(1), 01-19.