Abstract

Statement of PurposeAll implanted materials induce an immune response driven by macrophages called the foreign body reaction (FBR). Macrophages exist in a continuum of highly inflammatory to highly pro‐wound healing phenotypic cell types. This project aims to assess macrophage activation patterns caused by implanted polyvinyl alcohol non‐biodegradable vs. collagen biodegradable sponges in the subcutaneous space of male Sprague Dawley rats. Our hypothesis is that macrophages interact differently between different materials. If such difference exists, this means the approaches to driving macrophages to their wound healing states would be expected to be different. This study included the delivery of previously tested drug modulators, dexamethasone and iloprost, for their ability to shift macrophages to their pro‐wound healing state. The use of these modulators enables screening and comparing the effect of biomaterial chemistry on macrophage activation patterns.MethodsMale Sprague‐Dawley rats, (250 – 290) grams, were divided into three groups (6 animals in groups #1 and #2 and 4 animals in group #3) where PVA sponges were soaked in either the vehicle solution (lactate Ringers' solution) in group #1 (control group), 100 μM dexamethasone in group #2 (treatment group), or 1 nM iloprost in group #3 (treatment group). Two PVA sponges were implanted in the dorsal subcutaneous space of each animal. A daily booster dose of the assigned treatment was administered subcutaneously into each implantation site 24 hours after implantation until experiment completion. A week after implantation, sponges and surrounding tissue were harvested for either histological/immunohistochemical analysis or CCL2 quantification.ResultsC‐C motif chemokine ligand 2 (CCL2) levels averaged around 800, 450, and 300 ng/mL in the wound fluid collected from the control, iloprost treated, and dexamethasone‐treated sponges, respectively. The levels of CCL2 in the wound fluid collected from the dexamethasone‐treated sponges and those collected from the iloprost treated sponges were found to be significantly less than the wound fluid levels of CCL2 from the control sponges. No significant difference was found between the wound fluid levels of CCL2 from dexamethasone‐treated sponges vs. iloprost‐treated sponges (Figure 1).Less cellular density and less collagen formation were observed in the tissues surrounding both iloprost treated sponges and dexamethasone‐treated sponges compared to the tissues around the control sponges (Figure 2).The total protein concentrations in the wound fluid collected from control and treatment sponges were similar within each animal and ranged between 40–50 mg/mL.Additional experiments are needed to determine the macrophage activation response after the implantation of collagen bio‐degradable sponges and compare it to macrophage activation response after the implantation of PVA non‐biodegradable sponges.Support or Funding InformationProvost's Collaborative Research Grant at University of ArkansasThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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