Topical application of complement C3 in collagen formulation increases early wound healing

Abstract

Background: The complement system is composed of bactericidal and hemolytic proteins that increase capillary leakage and inflammatory cell migration. The role of complement C3 to augment wound healing has not yet been studied. Methods: We examined the effects of topical complement C3 formulation at two concentrations (10 and 100 nM) on the rat surgical skin incision model. Skin was examined for maximal breaking strength and sectioned for histological examination. Fibronectin and collagen I content were measured using western blot analysis. Results: There was a statistically significant 74% increase in maximum wound strength with the topical application of 100 nM of C3 at day 3 (850 ± 138 g) when compared to the control rats (490 ± 57 g). Histological correlation was seen with an increased inflammatory cell and fibroblast infiltration in treated wounds as compared to control rats as early as 3 days post-wounding. Western blots revealed increased fibronectin and collagen I levels in C3 treated wounds. Conclusions: Topical application of complement C3 in collagen formulation to skin wounds significantly increases wound healing as early as 3 days after wounding. This is correlated with increased inflammatory cell recruitment and the subsequent early fibroblast migration and increased collagen deposition and organization in wounds.

Key words::

• complement C3
• cutaneous
• skin
• rat
• wound healing

Acknowledgments

We would like to acknowledge financial support from Dr. Bruce Williams Division of Plastic Surgery Research Funds and the Canadian Institute of Health Research (CIHR) to Dr. S Prakash. We also acknowledge the National Sciences and Engineering Research Council of Canada (NSERC) and the McGill University Surgeon Scientist Fast Family Research Fund, and the Division of Plastic Surgery Research Fund to Dr. Hani Sinno. We would also like to thank Pina Sorrini for her excellent secretarial help. We thank Genevieve Berube, Karen Zwiker, and the McGill University Animal Research Center Staff for their professional help with animal handling. We would also like to acknowledge the technical support of the McGill University Orthopedic Research Laboratory and the Small Animal Imaging Laboratory staff for their excellent technical support. Financial Disclosure: We would like to acknowledge financial support from Dr. Bruce Williams Division of Plastic Surgery Research Funds and the Canadian Institute of Health Research (CIHR) to Dr. S Prakash. We also acknowledge the National Sciences and Engineering Research Council of Canada (NSERC) and the McGill University Surgeon Scientist Fast Family Research Fund, and the Division of Plastic Surgery Research Fund to Dr. Hani Sinno. The authors have no commercial associations or financial disclosures that may pose or create a conflict of interest with information presented in this manuscript.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.