Development and preclinical evaluation of a dual therapeutic platform for skin applications
Résumé
Introduction Skin disorders, such as chronic wounds, atopic dermatitis or psoriasis, are often associated with oxidative stress and bacterial infections, which contribute to impaired healing and disease progression. The combined challenge of oxidative stress and infection, along with the increasing prevalence of multidrug-resistant pathogens, underscores the urgent need for innovative dual-targeted therapies. This work presents the development of a platform integrating an elastomeric scaffold filled with an alginate hydrogel incorporating two Staphylococcus aureus bacteriophages (ISP & GRCS) and curcumin-loaded nanostructured lipid carriers (CUR-NLCs) for antioxidant properties. This multifunctional approach is designed to address both infection and oxidative stress. Materials and Methods The elastomeric poly(glycerol sebacate) (PGS) scaffold was fabricated using a salt-leaching technique. Alginate formulations loaded with CUR-NLCs and bacteriophages (ISP and GRCS) were gelled in situ within the scaffold’s cavities. The resulting platform was mechanically and morphologically characterized by compressive strength tests and scanning electron microscopy (SEM). The release of curcumin and active bacteriophages was determined by spectrophotometry and double agar overlay assay respectively. Preclinical evaluation included an MTS assay on human fibroblasts (BJ) and human keratinocytes (HEKn), along with histological analysis using a reconstructed human epidermis model (SkinEthic RHE). Antibacterial and antioxidant activity were performed by CFU counting and ABTS assay respectively. Results PGS scaffolds were successfully filled with alginate formulations without compromising the lytic activity of bacteriophages, with loading efficiency superior to 80%. Furthermore, hydrogel formation within the scaffold’s pores was confirmed by SEM. The final platform, incorporating CUR-NLC and bacteriophages, exhibited good elasticity recovery and Young’s modulus comparable to human skin. Furthermore, sustained release of active phages was observed, with concentrations exceeding 60 % (< 10⁹ PFU/mL) after 72 hours. Cytotoxicity assays confirmed the absence of toxicity in human skin fibroblasts (BJ) and keratinocytes (HEKn). Biocompatibility was further assessed using a reconstructed human epidermis model (SkinEthic RHE) to evaluate potential skin irritation and effects on epidermal metabolic activity and barrier integrity. Finally, the platform’s therapeutic efficacy was evaluated by studying its antibiofilm activity against methicillin-resistant Staphylococcus aureus strains and antioxidant activity. Discussion The successful incorporation of the alginate hydrogel with bioactive agents within PGS scaffolds highlights the platform’s versatility. Its preserved structural integrity, favorable mechanical properties, and demonstrated biocompatibility further confirming its suitability for skin applications. Further studies are needed to fully explore its dual therapeutic potential. Conclusions The developed bifunctional platform stands out by integrating both properties into a single system, compared to conventional treatments. It represents a promising approach as a novel adjuvant therapy for the treatment of skin disorders by simultaneously targeting bacterial infections and inflammation. Its ability to sustain the release of bioactive agents while maintaining biocompatibility makes it a potential candidate for advanced wound care applications. Future in vivo studies are necessary to confirm its therapeutic benefits and evaluate its long-term stability.