Poly(lactide acid)-based microneedles enhanced by tunicate cellulose nanocrystals for potential diabetic periodontitis treatment.

Diabetic periodontitis, characterized by persistent inflammation and impaired periodontal tissue regeneration under hyperglycemic conditions, urgently requires innovative therapeutic strategies. Microneedle (MN) technique has recently emerged as a promising solution for diabetic periodontitis by enabling minimally invasive and localized drug delivery. In this study, we developed poly(lactic acid) (PLA)-based MNs reinforced with PLA-grafted tunicate cellulose nanocrystals (TCNC-g-PLA@PLA-MNs), demonstrating favorable mechanical strength and biocompatibility. After loading with irisin and interleukin-1 (IL-1) receptor antagonist (IL-1ra) via surface polydopamine functionalization, the MNs exhibited anti-inflammatory effects by markedly reducing the expressions of IL-6 by 0.53-fold, IL-8 by 0.23-fold, and MCP-1 by 0.41-fold in human periodontal ligament cells (hPDLCs). Additionally, they significantly promoted osteogenic differentiation, increasing the expressions of ALP by 1.87-fold, OPN by 2.21-fold, OCN by 1.39-fold, and Runx2 by 2.28-fold, which was further supported by enhanced ALP staining. Furthermore, the MNs improved the migration ability of hPDLCs under inflammatory and high-glucose culture conditions. Our findings highlight that the TCNC-g-PLA@PLA-MNs effectively integrate structural reinforcement and therapeutic functionality, providing a novel and potential platform to promote periodontal regeneration in the context of diabetic periodontitis.