3D bioprinting strategies for diabetic wound healing: Functional bioinks, vascularization, and immune modulation

Diabetic wounds, especially diabetic foot ulcers, remain a significant clinical and economic challenge, largely due to compromised angiogenesis, persistent inflammation, and delayed tissue repair. Conventional therapies often fail to address the complex nature of these wounds, which leads to prolonged healing, increased infection risk, and chances of limb amputation. Three-dimensional (3D) bioprinting has emerged as a promising approach in treating diabetic wounds, offering precise fabrication of skin substitutes that recapitulate native skin architecture and function. Recent advances in 3D bioprinting strategies have focused on three critical areas: the development of functional bioinks, promotion of vascularization, and the modulation of immune responses. Functional bioinks typically formulated with combinations of natural and synthetic polymers are designed to support cell viability, simulate the extracellular matrix, and deliver bioactive agents such as growth factors, oxygen-generating materials, or nitric oxide donors. Vascularization strategies frequently involve co-printing with endothelial cells or incorporating angiogenic factors to restore tissue perfusion and facilitate integration. Simultaneously, immune-modulatory approaches are employed to resolve chronic inflammation and create a more regenerative wound microenvironment. This review presents a comprehensive overview of 3D bioprinting strategies for diabetic wound healing by discussing three essential domains: functional bioinks, vascularization strategies, and immune modulation. It provides a unified framework that reflects the complex nature of chronic wound repair. Ongoing progress in biofabrication, material science, and regulatory frameworks will be vital for translating these innovative technologies into effective clinical interventions for diabetic wound healing.