A Patch of Detachable Hybrid Microneedle Depot for Localized Delivery of Mesenchymal Stem Cells in Regeneration Therapy

Mesenchymal stem cells (MSCs) have been widely used for regenerative therapy. In most current clinical applications, MSCs are delivered by injection but face significant issues with cell viability and penetration into the target tissue due to a limited migration capacity. Some therapies have attempted to improve MSC stability by their encapsulation within biomaterials; however, these treatments still require an enormous number of cells to achieve therapeutic efficacy due to low efficiency. Additionally, while local injection allows for targeted delivery, injections with conventional syringes are highly invasive. Due to the challenges associated with stem cell delivery, a local and minimally invasive approach with high efficiency and improved cell viability is highly desired. In this study, a detachable hybrid microneedle depot (d-HMND) for cell delivery is presented. The system consists of an array of microneedles with an outer poly(lactic-co-glycolic) acid shell and an internal gelatin methacryloyl (GelMA)-MSC mixture (GMM). The GMM is characterized and optimized for cell viability and mechanical strength of the d-HMND required to penetrate mouse skin tissue is also determined. MSC viability and function within the d-HMND is characterized in vitro and the regenerative efficacy of the d-HMND is demonstrated in vivo using a mouse skin wound model.