Synergistic integration of exosomes and natural compounds in 3D-printed bioscaffolds: Revolutionizing diabetic wound...

Chronic wounds associated with diabetes, particularly diabetic foot ulcers, are a common complication and a significant public health challenge because they heal slowly and carry a high risk of amputation. Non-healing diabetic wounds are linked to local infection, compromised immune function, vascular damage, nerve impairment, and fragile peripheral skin. Exosomes derived from stem cells share many biological effects with their source cells but have lower immunogenicity and no tumorigenic potential, while demonstrating enhanced effectiveness in promoting wound healing. Exosomes enhance wound healing by stimulating angiogenesis and cell proliferation and by regulating inflammation. When genetically modified or combined with materials, exosomes exhibit improved therapeutic capabilities, including enriched active components, targeted delivery, and enhanced penetration across physiological barriers, thereby surpassing the limitations of conventional single treatments. Natural compounds with medicinal properties have demonstrated the capacity to facilitate tissue repair. Extensive research has examined the regenerative potential of plant-based and naturally occurring substances with inflammation-reducing, oxidative stress-mitigating, pathogen-inhibiting, and collagen-enhancing properties. 3D bioprinting, an additive manufacturing technique guided by computer-generated designs, produces biocompatible 3D structures. These tissue-engineered dermal replacements outperform conventional wound-healing techniques by offering greater procedural consistency, regulatory-compliant manufacturing standards, and precise delivery of living cellular elements, signaling proteins, and bioactive compounds. This review aims to explore the synergistic integration of exosomes and natural compounds within 3D-printed bioscaffolds for diabetic wound healing. It highlights the multifunctional therapeutic potential of these advanced platforms in enhancing tissue regeneration and repair. The article also discusses current challenges and future perspectives in translating these innovative strategies into clinical applications.