Potential of 3D Printing in Fabrication of Patient-Specific Biodegradable Microneedle Platform for Alopecia Treatment

A wide range of environmental and genetic factors have been identified as responsible causes leading to androgenetic alopecia. Despite the considerable therapeutic advancements, however, current alopecia treating compounds have limited effectiveness and may result in distant hypertrichosis, irritation, and sexual dysfunction side effects. Valproic acid, a widely used FDA-approved anticonvulsant drug, was reported to induce hair regrowth with remarkable higher effectiveness compared with Minoxidil, the most widely marketed hair loss treating agent. Valproic acid activates several signaling pathways, including the Wnt/β-catenin pathway, an essential pathway in hair morphogenesis. On the other hand, a growing body of evidence suggests β-catenin expression is elevated during the proliferative phase of wound re-epithelialization. Therefore, we hypothesized application of valproic acid encapsulated microneedles into the skin, (I) delivers valproic acid with higher efficiency compared with topical application, and (II) results in micro dimension wounds which would upregulate expression of β-catenin at the application site.<br/>To evaluate our hypothesis, we shaved dorsal skin of 7-week-old mice at telogen phase and treated it with either topical control, topical valproic acid, microneedle control, or valproic acid encapsulated microneedle. Microneedles were fabricated with a total height of 600 μm in 7 × 7 arrays. Our results confirmed that valproic acid encapsulated microneedles induced hair regrowth more effectively than topically applied valproic acid. Interestingly, we found that dermal thickness was more variable and thicker in mice treated with microneedle control compared with topical control, suggesting the impact of micro-wounds on hair regrowth. Further evaluation of dermis and hair follicle markers confirmed elevated expression of β-catenin, loricrin, K15, CD34, and ALP in valproic acid encapsulated microneedles compared with topical valproic acid and in microneedle control compared with control topical formulation.<br/>Based on the findings of this study, we are currently developing 3D printed patient-specific microneedle platforms that can be tailored based on the hair loss pattern of patients. The number of microneedles and their arrangement can be simply adjusted using CAD software and the encapsulation dosage of valproic acid within the 3D printed microneedle platform can be adjusted during the mold casting process.