Panthenol Citrate Biomaterials Accelerate Wound Healing and Restore Tissue Integrity

The global surge in diabetes has led to diabetic foot ulcers (DFU) becoming a predominant diabetes-related complication, resulting in hospitalizations and, in severe cases, lower limb amputations. A staggering 34% of individuals with diabetes will encounter a DFU during their lifetime, with 15-20% becoming chronic or non-healing wounds. These wounds differ significantly from normal wounds, plagued by persistent oxidative stress, abnormal inflammatory responses, impaired vascularization, and innervation, among other patient-specific challenges. Furthermore, suboptimal physical properties of regenerated tissue often lead to recurrent or reopened wounds, with alarming statistics indicating recurring DFUs may result in amputation in 71-85% of cases. Meeting the pressing need for wound treatments that not only expedite wound closure but also enhance the quality of regenerated tissue is paramount in improving diabetic wound care outcomes. In this study, we present the synthesis and characterization of panthenol citrate (PC), a versatile compound with potential applications in soluble form as a cleansing solution and as a regenerative dressing to address impaired wound healing in diabetes. PC is derived by reacting citric acid with panthenol, offering intriguing optical, chemical, and biological properties conducive to protecting and regenerating skin tissue. With citric acid's established safety record and panthenol's known skin benefits, PC represents a promising candidate. PC demonstrates antioxidant, antibacterial, anti-inflammatory, and proangiogenic properties, facilitating wound closure in diabetes while restoring skin's mechanical and electrophysiological properties. In both solution and hydrogel forms, PC stimulates keratinocyte and dermal fibroblast migration and proliferation, resulting in improved re-epithelialization, granulation tissue formation, and accelerated wound closure. Remarkably, PC significantly enhances the mechanical strength and electrophysiological properties of regenerated skin. To our knowledge, this is the first study to demonstrate such comprehensive improvements in the histological and physical properties of regenerated skin following treatment with both monomeric and polymeric forms of a compound. Our approach encompasses the utilization of PC as a wound cleansing solution or as a component of a thermoresponsive biomacromolecule for use as a regenerative dressing. In conclusion, PC emerges as a pivotal building block for advanced tissue regeneration therapies, holding the promise of markedly improving wound care management for diabetic patients.