Nanotechnology invigorated drug delivery and tissue engineering strategies for the management of diabetic foot ulcers: Therapeutic approaches and clinical applications

Diabetic foot ulcers (DFUs) are multifactorial pathological manifestations in diabetes patients that cause foot deformities, ultimately leading to limb amputation. Various therapeutic strategies such as debridement therapy, pressure off-loading, revascularization, low-level laser therapy, hyperbaric oxygen therapy, negative pressure wound therapy, along with wound dressings or anti-microbial therapy are being explored for the management of DFUs. Further, bioactive phytochemicals, growth factors, and repurposed drugs are being employed as alternative strategies. The emergence of nanotechnological interventions in biology and medicine brought a paradigm shift in the clinical management of DFUs. Nanotechnology-based therapeutic interventions help in better presentation of therapeutics at the wound site, thereby augmenting tissue remodelling and regeneration. This review discusses pathophysiology and nanotechnological interventions such as nanoparticles, nanofibers and 3D bioprinting for the management of DFUs. In addition, special emphasis on currently available clinical interventions have been highlighted. Further, hurdles in bench-to-bedside translation, limitations of available animal models, and regulatory perspectives have been emphasized.