The Effect of Vitamin C on Wound Healing In Mandibular Fracture Patients: A Double Blind, Placebo-controlled Randomized Clinical Trial

In a prospective, randomized clinical trial of de novo mandibular fracture patients requiring intraoral surgical repair with plating, the investigators will:

1. Compare the effects of supplemental vitamin C to placebo on soft tissue wound healing, measured by a) biomarkers of soft tissue repair (Procollagen I and III, Matrix Metallo-Proteinases 1,2,3 & 9, C-reactive protein, neutrophil count, Interleukins 6 & 8, TBARS and TEAC) and b) clinical outcomes (wound dehiscence and Wound Score).

Hypothesis1: Supplemental vitamin C will improve soft tissue healing post-mandibular fracture, measured by improved procollagen I, other biomarker levels and clinical outcomes, compared to placebo.

Rationale. The clinical literature describes impaired soft tissue wound healing in mandibular fracture patients, including wound infection, wound dehiscence, and plate exposure. Vitamin C is a necessary co-factor for the production of types I and III collagen, as well as procollagen, the precursor to collagen, via the hydroxylation of proline and lysine. In the setting of vitamin C deficiency, collagen production is abnormal leading to defective vessel and connective tissue formation with degradation of unstable collagen molecules.90-91,34, 63, 108,109

The investigators will collect a robust set of clinical outcomes including clinician evaluation and Wound Healing Score to measure soft tissue healing. Biomarkers of soft tissue wound healing will be used to measure biochemical healing pathways as well. As a precursor to collagen, procollagen I and III are widely used biomarkers of collagen production in wound healing research. The investigators will assess these levels at baseline and at 3 to 5weeks post-operatively to evaluate the effect of vitamin C on collagen production. In addition, the antioxidant effects of vitamin C are critical during the ordered phases of wound healing, from the inflammatory phase (including the initial hemostatic cascade) to the proliferative phase. Antioxidant depletion during these phases results in imbalanced proteolytic enzyme cascades (including matrix metalloproteinases or MMPs) with resulting tissue destruction as well as an over-exuberant inflammatory milieu. Further, the antioxidant deficit resulting from vitamin C deficiency results in diminished monocyte and neutrophil chemotaxis and diminished bacteriocidal oxidative burst capabilities. Thus, the investigators will additionally measure the effects of vitamin C supplementation on proteolytic enzyme pathways (MMPs) and systemic markers of infection and inflammation (neutrophil count, c-reactive protein level, interleukins (IL) 1 and 6). Finally, the investigators will use indicators of oxidative stress at baseline and 6 weeks to measure the effects of vitamin C supplementation on antioxidant capacity (TBARS and TEAC). 2. Compare the effects of supplemental vitamin C to placebo on bone repair, measured by a) biomarkers of bone repair (alkaline phosphatase, TRACP 5b, osteocalcin, RANKL, osteoprotegerin, and carboxy terminal collagen crosslinks) and b) clinical outcomes (radiologic imaging and pain).