Antioxidant-antibacterial containing bi-layer scaffolds as potential candidates for management of oxidative stress and infections in wound healing
Tissue engineering techniques are continuously evolving towards providing better microenvironment along with therapeutic potential to address the skin tissue defects. Factors such as microbial infections, presence of excessive free radicals and depletion in antioxidant based scavenging systems pose serious challenges by prolonging inflammation and delaying the repair process. Incorporation of bioactive molecules in polymer based biomimetic scaffolds may present new vistas for handling chronic wounds. In this study, chitosan/collagen scaffolds incorporating 0.5, 1 and 2% (w/w) silymarin (CS-CO-SM) were synthesized and studied for their biocompatibility, in vitro release kinetics and anti-oxidant activity. The release kinetics of silymarin from the CS-CO-SM scaffold showed an initial burst followed by sustained release. The scaffolds were biocompatible and supported the recovery of COS-7 cells from UV induced oxidative stress. Further the CS-CO-SM(2) scaffolds were used to fabricate a bi-layer scaffold by layer upon layer arrangement with CS-Ag3 (3% Ag, w/w). The Ag was incorporated to impart antimicrobial property to the scaffold. The in vivo studies on bi-layer scaffolds were carried out in Wistar rat models at 3, 7 and 10 days post injury and the skin excisions were studied for wound contraction, histology (H&E staining), and lipid peroxidation. The bi-layer scaffold accelerated the process of wound healing with no inflammatory cells, proliferation of fibroblast, neovascularization and collagen deposition. By day 10 post transplantation of the scaffold, the skin had a structure similar to normal skin with complete re-epithelization. This bi-layer scaffold with antioxidant and antimicrobial properties promotes wound healing and is proposed as a potential tissue engineering material for managing chronic wounds.
The authors would like to acknowledge Mr. Joseph RD Fernandes and Dr. Arnab Banerjee for the kind support in immunohistochemical staining. The authors also want to acknowledge the central facility, BITS Pilani K K Birla Goa Campus for the help in characterization of the scaffolds, Dr. Chandrashekhar S. Mote for the histological evaluation of skin grafts and Agharkar Research Institute, Pune for the animal studies experiments.
Conflict of interest
The authors declare that they have no conflict of interest.
- 14.Bryan N, Ahswin H, Smart N, Bayon Y, Wohlert S, Hunt JA. Reactive oxygen species (ROS)–a family of fate deciding molecules pivotal in constructive inflammation and wound healing. Eur Cell Mater. 2012;24:e65Google Scholar
- 16.Lee Y-H, Chang J-J, Chien C-T, Yang M-C, Chien H-F. Antioxidant sol-gel improves cutaneous wound healing in streptozotocin-induced diabetic rats. Exp Diabetes Res. 2012;2012:1–11.Google Scholar
- 30.Pundir S, Badola A, Sharma D. Sustained release matrix technology and recent advance in matrix drug delivery system: a review. Int J Drug Res Technol. 2017;3:8.Google Scholar
- 41.Sherif IO, Al-Gayyar MM. Antioxidant, anti-inflammatory and hepatoprotective effects of silymarin on hepatic dysfunction induced by sodium nitrite. Eur Cytokine Netw. 2013;24:114–21.Google Scholar
- 42.Nielsen F, Mikkelsen BB, Nielsen JB, Andersen HR, Grandjean P.Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin Chem. 1997;43:1209–14.Google Scholar