Silk fibroin microparticles as a candidate for wound healing applications: evaluating the role of adenosine

In this study, silk fibroin (SF) aerogel microparticles were developed as a delivery system for adenosine (ADO) to exploit its anti-inflammatory and regenerative properties for wound healing. Supercritical CO₂ drying was used to prepare ADO-loaded SF aerogel microparticles with different SF concentrations (3 %, 5 %, 7 % w/v) and SF:ADO ratios (10:1, 5:1, 2:1). Characterization revealed high porosity (91-94 %), interconnected pores, high skeletal density (1.22-1.32 g/cm³) and significant surface area (191-306 m²/g). Notably, the 5 % SF with a 5:1 SF:ADO ratio emerged as the most promising formulation, exhibiting excellent morphological and biological properties (91 % porosity, 1.31 g/cm³ skeletal density, and 191 m²/g surface area). In vitro studies on human dermal fibroblasts (HDF), keratinocytes (HaCaT), and human dermal microvascular endothelial cells (HDMEC) demonstrated enhanced viability and proliferation in HDF and HaCaT cells. Specifically, the 5 % SF 5:1 and 5 % SF 2:1 formulations significantly boosted proliferation (over 100 % compared to control) for up to 7 days, highlighting their potential. While HDMECs showed sensitivity to higher ADO concentrations (observed with the 5 % SF 2:1 formulation), the 5 % SF 5:1 formulation achieved the most balanced cellular response across all cell types, underscoring the importance of precise dosage. These findings support the potential of ADO-loaded SF aerogel microparticles in tissue regeneration applications. Further in vivo studies are needed to validate therapeutic efficacy and benchmark against existing wound healing treatments.