Complements C3 and C5 Individually and in Combination Increase Early Wound Strength in a Rat Model of Experimental Wound Healing

Background. Complements C3 and C5 have independently been shown to augment and increase wound healing and strength. Our goal was to investigate the combinatorial effect of complements C3 and C5 on wound healing. Methods. Each rat served as its own control where topical collagen was applied to one incision and 100？nM of C3 and C5 in collagen vehicle was applied to the other incision ( ). To compare between systemic effects, a sham group of rats ( ) was treated with collagen alone on one wound and saline on the other. At day 3, the tissue was examined for maximal breaking strength (MBS) and sectioned for histological examination. Results. There was a statistically significant 88% increase in MBS with the topical application of C3C5 when compared to sham wounds ( ). This was correlated with increased fibroblast and collagen deposition in the treated wounds. Furthermore, there appeared to be an additive hemostatic effect with the C3C5 combination. Conclusions. The combination of complements C3 and C5 as a topical application drug to skin wounds significantly increased wound healing maximum breaking strength as early as 3 days. 1. Introduction Wound healing can be problematic in several clinical settings. The current available surgical and medical options are not always ideal for all patients. The development of a novel therapeutic agent that may help augment the healing process is urgent. An understanding of the intricate cascade of events and cellular interactions is essential in the development of such therapeutic agents. The complement cascade involves the interaction and cleavage of eleven proteins to form complexes responsible for hemostasis, chemotaxis, and bacterial lysis [1]. Complements C3 and C5 have independently been shown to play a role in wound healing, augmenting wound strength, and increasing cellular infiltration and collagen deposition [2, 3]. Furthermore, C5 has been shown to accelerate healing by at least four days in the first week of wounding [3]. The synergistic effect of combining C3 and C5 to augment wound healing is not yet known. We aim to decipher the potential synergistic effects that C3 and C5 may have on wound healing strength. Our objective is to combine C3 and C5 as a topical therapeutic agent to assess changes in wound strength and cellular infiltration. The potential synergistic effect on wound healing can be potentially a great advancement in the understanding of the complex processes of wound healing and translation to a novel therapeutic agent for the use and benefit for patients. 2. Materials and Methods 2.1. In Vivo