Enhanced Bacterial Nanocellulose Scaffolds in Diabetic Wound Healing

A Review of Pathophysiology, Current Modalities, and Advanced Tissue Engineering Strategies

Abstract

Diabetic foot ulcers (DFUs) and chronic non-healing wounds present a profound clinical challenge, driven by a complex, interconnected pathophysiology characterized by persistent inflammation, impaired angiogenesis, extracellular matrix (ECM) degradation, and dysfunctional cellular responses. Conventional treatment approaches often fail to address this hostile microenvironment. In recent years, tissue engineering and regenerative medicine have emerged as pivotal paradigms, shifting the focus toward bioactive, smart biomaterials. Among these, bacterial nanocellulose (BNC)—a highly pure exopolysaccharide synthesized by bacteria such as Komagataeibacter xylinus—has garnered significant attention due to its nanofibrillar network, high water-retention capacity, biocompatibility, and mechanical integrity. However, pristine BNC lacks inherent antimicrobial activity and specific cell-instructive motifs. This review comprehensively examines the molecular mechanisms underlying diabetic wound recalcitrance and systematically evaluates current and emerging therapeutic modalities. We critically analyze the structural advantages of BNC and explore state-of-the-art functionalization strategies, including composite formulation, growth factor loading, and cellular seeding. By integrating bioactive macromolecules and therapeutic cells, enhanced BNC scaffolds serve as a dynamic, synergistic platform capable of modulating the chronic wound bed and accelerating functional tissue regeneration.