Dodecenylsuccinic anhydride modified collagen hydrogels loaded with simvastatin as skin wound dressings

Abstract

Skin wound healing presents a unique challenge because of its complex healing process. Herein, we developed a hydrophobic wound dressing to incorporate simvastatin, which has potential application in the treatment of ulcers and prevention of wound infection. For that matter, collagen hydrogels were grafted with dodecenylsuccinic anhydride (DDSA). The chemical modification was confirmed by FTIR and solid state 13C-NMR spectroscopies while the ultrastructure was observed by scanning electron microscope (SEM) images. In contact angle measurements, a higher water droplet angle in DDSA-collagen gels was observed. This was consistent with the swelling assay, in which water absorption was 5.2 g/g for collagen and 1.9 g/g for DDSA-collagen. Additionally, viability and adhesion studies were performed. Cell adhesion decreased ~11% in DDSA-collagen and the number of viable cells showed a tendency to decrease as DDSA concentration increased but it was only significantly lower above concentrations of 12%. Modified gels were loaded with simvastatin showing higher adsorption capacity and lower release. Lastly, the antimicrobial and anti-inflammatory activity of DDSA-collagen materials were assessed. DDSA-collagen hydrogels, either unloaded or loaded with simvastatin showed sustained antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus for 72 hr probably due to the hydrophobic interaction of DDSA chains with bacterial cell walls. The antimicrobial activity was stronger against S. aureus. Collagen hydrogels also presented a prolonged antibacterial activity when they were loaded with simvastatin, confirming the antimicrobial properties of statins. Finally, it was observed that these materials can stimulate resident macrophages and promote an M2 profile which is desirable in wound healing processes.