Clinical parameters available to evaluate early healing phases of bone regeneration procedures are limited. This study explores wound fluid content for molecular markers to differentiate wound healing responses in the early postoperative period of bone regeneration procedures. Fifteen patients (50±5 yrs old; 8 males) scheduled to receive tooth extraction and bone graft placement at maxillary non-molar single tooth sites were recruited. Primary wound closure was not intended at time of surgery. Gingival Crevicular Fluid (GCF) from adjacent teeth or Wound Fluid (WF) from surgical wound edges were collected (30 sec) at baseline, 3, 6, 9 days, 1 and 4 months. Multiplex protein assay was used to determine concentration of various wound healing mediators. Immediately post-surgery, 87% of surgical sites exhibited open wound. At day 9, mean wound exposure was 4.8±0.4 mm. At 1 month, all wounds were clinically closed. WF tripled in volume at day 3 and day 6 (p≤0.05), compared to baseline GCF, and gradually decreased as wounds closed. WF concentrations of IL-6, PlGF, PAI-1, IGFBP-1 and sCD40L were increased during early healing days, generally with peak concentration at day 6 (p≤0.004). Conversely, WF concentrations of IL-18 and EGF were decreased following surgery, generally not reaching baseline values until wound closure (p≤0.008). In general, WF cytokine expression kinetics were concordant with wound closure dynamics (p≤0.04). These results suggest that wound fluid molecular markers such as IL-6, and to a lesser extent PIGF and IL-18, might help differentiate wound healing responses after bone regeneration procedures.

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