Controlled therapeutic cholesterol delivery to cells for the proliferation and differentiation of keratinocytes†

The challenge of enhancing wound healing and skin regeneration, particularly in conditions like burns and diabetic wounds, necessitates innovative solutions. Cholesterol, often associated with cardiovascular diseases, plays vital roles in cellular functions, maintaining skin integrity and preserving the skin barrier. Here, we explore cholesterol's significance, its influence on keratinocytes, and its potential application in skin regeneration. The study utilizes electrospun polyimide (PI) fibers as a cholesterol carrier model and investigates its impact on HaCaT keratinocytes, marking the first time tracked cholesterol delivery from the scaffold into cells. We demonstrate that an optimal concentration of 0.7 mM cholesterol in the medium enhances cell proliferation, while higher concentrations have negative effects. Cholesterol-enriched scaffolds significantly increase cell proliferation and replicative activity, especially in a 3D culture environment. Moreover, cholesterol influences keratinocyte differentiation, promoting early differentiation while inhibiting late differentiation. These findings suggest that cholesterol-loaded scaffolds can have applications in wound healing by promoting cell growth, regulating differentiation, and potentially accelerating wound closure. Further research in this area will lead to innovative wound management and tissue regeneration strategies.