Modular Microneedle Patch for Local Immunomodulation and Periodontal Tissue Regeneration

Abstract

Periodontal diseases affect over 50% of people and are caused by microbial infection and the recruitment of destructive immune cells such as macrophages and T cells. Current therapies for periodontitis mainly deal with bacteria elimination, but immunomodulation and tissue regeneration remains a challenge. Here we developed a modular and multifunctional microneedle (MN) patch that can deliver small molecules and immunomodulatory cytokines into the local gingival tissue. This MN patch included a quickly dissolvable gelatin membrane for a burst release of tetracycline and biodegradable GelMA microneedles that contained poly(lactic-co-glycolic acid) nanoparticles and silica microparticles for a sustained release of tetracycline and cytokines respectively. Antibiotic release completely inhibited bacteria growth, and the sustained release of IL-4 and TGF-β induced the repolarization of anti-inflammatory macrophages and the formation of regulatory T cells in vitro. In vivo placement of MN patch into periodontal tissues not only reduced local inflammatory signals but also modulated local immune cells to promote tissue healing. This work demonstrated a modular MN delivery platform for immunomodulation and tissue regeneration, which will have broad applications in regenerative medicine.