Activated collagen accelerates wound repair and modulates cytokine production in whole blood and PBMC cultures

Abstract

Several reports have shown that exogenous collagen fragments enhance wound repair through poorly understood mechanisms. CellerateRX is an activated (fragmented) product derived from Type I Collagen that is applied topically as a gel or powder on open wounds that are often infected or colonized with bacteria. In three case series, topical CellerateRX in conjunction with standard care healed infected surgical wounds and diabetic ulcers more rapidly than standard therapy alone. We conducted an interim analysis of 16 patients with lower extremity diabetic ulcers. Eight patients received CellerateRX in addition to standard treatment, and 8 received standard treatment alone. A quantitative analysis of wound healing at 14 weeks showed that CellerateRX-treated wounds were 100 0% healed, compared to 59 13.5% healing in control subject wounds. To examine possible mechanisms by which CellerateRX enhances wound healing, cytokine production was assessed in 24 hr cultures of whole blood and peripheral blood mononuclear cells (PBMC) from 10 healthy subjects. These cultures were conducted in the absence or presence of stimulation with heat-killed Staphylococcus epidermidis (S.epi) or lipopolysaccharide (LPS). In whole blood, CellerateRX significantly increased spontaneous production of Interleukin (IL)-8, IL-6, IL-1 , tumor necrosis factor (TNF ), and IL-10. In whole blood stimulated with S.epi, cytokine synthesis was augmented by CellerateRX, except for TNF , which was suppressed. In PBMC cultures, CellerateRX significantly induced spontaneous production of IL-8, IL-6, IL-1 , TNF and IL-10. In PBMC stimulated with LPS, CellerateRX significantly augmented IL-8, IL-6, and IL-10; TNF was suppressed. CellerateRX inhibition of stimulated TNF in whole blood and PBMC suggests selective suppression of detrimental TNF inflammatory and cell death effects in vivo. These results suggest that CellerateRX enhances wound healing, and a possible mechanism involves specific modulation of the cytokine response in bacteria-containing wounds.