Research Projects

Suckerin protein, derived from squid sucker ring teeth, is an ideal biomaterial for wound healing due to its adaptable mechanical properties, with a tunable elastic modulus from 40 Pa in hydrogels to several GPa in crosslinked films. Its β-sheet structure enables strong, moisture-resistant adhesion with an adhesive work of ~15 mJ/m², making it superior to traditional materials like silk fibroin and collagen, which lack stability in dynamic wound conditions. These properties position suckerin as highly suitable for wound dressings requiring stable adhesion and mechanical resilience. In diabetic wounds, chronic inflammation is a major obstacle to healing, largely due to the activation of the NF-κB pathway by Interleukin-1 receptor-associated kinase 1 (IRAK1). IRAK1 activation promotes the release of pro-inflammatory cytokines, creating a non-healing environment that impedes tissue repair. Targeting IRAK1 offers a promising strategy to interrupt this inflammatory pathway and facilitate wound healing. miR146a, a microRNA, downregulates both IRAK1 and TRAF6, reducing cytokine production and promoting a regenerative environment. However, miR146a’s instability limits its direct application at the wound site. Exosomes, natural vesicles, provide a protective and controlled-release system for miR146a, maintaining stability and therapeutic efficacy upon delivery. Exosome-based delivery systems have shown success in reducing inflammation and enhancing wound healing. This study proposes an advanced wound dressing that combines suckerin’s mechanical resilience with miR146a-loaded exosomes to target IRAK1 inhibition in diabetic wounds. The study will proceed in three phases: (1) development of miR146a-loaded exosomes from human placental mesenchymal stem cells (PMSCs), (2) fabrication of a microporous suckerin patch using freeze-casting, incorporating miR146a-loaded exosomes, and (3) evaluation of the patch’s therapeutic efficacy in vitro and in vivo. RT-qPCR and western blotting will measure IRAK1 expression in diabetic wound fibroblasts to assess the patch’s inhibition of IRAK1. ELISA will quantify inflammatory cytokines (IL-1β, IL-6, TNF-α) in the medium, confirming the reduction of inflammation, while live/dead staining and MTT assays will test the patch’s biocompatibility and cell viability. In vivo, the suckerin-miR146a patch will be applied to full-thickness wounds on diabetic mouse models. Wound closure rates will be tracked over time using digital imaging. Histological analyses (Hematoxylin and Eosin, Masson’s Trichrome staining) will evaluate granulation tissue formation and collagen deposition, key indicators of wound healing. Immunohistochemical staining for angiogenesis (CD31) and inflammatory markers (IL-6, IRAK1) will assess vascularization and inflammation reduction. Results from this study will lay the foundation for clinical applications, advancing wound management and improving healing outcomes for diabetic patients.

chronic wound, miR146a, exosome, suckerin, IRAK1