43. Incorporation of Nitroglycerin into Acellular Dermal Matrix Hydrogel to Improve Perfusion to Skin Envelope in Implant-based Breast Reconstruction

PURPOSE: Mastectomy skin flap necrosis with implant-based breast reconstruction can be devastating resulting in additional procedures, implant infection and loss. Topical delivery of nitroglycerin (NTG) has been shown clinically to improve skin flap perfusion, decreasing rates of skin necrosis but meaningful transcutaneous delivery is limited to the first three post-operative days. Reactive vasodilatation and arteriogenesis within the skin flap can take 1-2 weeks necessitating sustained delivery to further improve outcomes. To improve the control and duration of NTG delivery, we investigate the utility of an injectable, ADM derived hydrogel as a vehicle for local sustained delivery of NTG in our murine model of ADM-assisted breast reconstruction. METHODS: C57BL/6 mice were randomly assigned to 50µg (n=6) and 100µg NTG dose groups (n=6). Dorsal subcutaneous pockets were created bilaterally, and ADM samples were implanted into each. Dermal hydrogels were then injected into the surgical pocket, with one side receiving the NTG loaded gel and contralateral side receiving a control hydrogel without NTG. Using laser Doppler imaging, skin perfusion was measured at implant sites pre- and post-operatively, daily through post-operative day (POD) 4, and again at POD 7, 14, and 21. At POD 21, ADM samples were harvested for histological analysis. RESULTS: Following elevation of the skin flaps, skin perfusion over the ADM implant decreased by 5.5% over pre-operative levels for the control group while 50µg and 100µg NTG loaded gels led to increases in skin perfusion of 19.5% and 8.7% respectively Skin perfusion peaked at POD 2 for all 3 groups with the 50µg NTG group showing a 65.9% increase over pre-op levels, the 100µg NTG group showing a 37.9% increase and the control group showing a 32.8% increase. 50µg NTG persisted in perfusion levels greater than 0µg controls over the critical 7 day post-operative period (33.1% at POD 1 and 56.6% at POD 7). However, perfusion in the higher 100µg NTG group remained similar (26.3% at POD 1 and 13.5% at POD 7) to the control group (16.9% at POD 1 and 34.6% at POD 7) during this time. Histology showed mononuclear and vascular invasion of all ADMs and normal overlying epithelial morphology. CONCLUSIONS: This model demonstrated that an ADM/hydrogel construct can serve as a delivery agent for NTG resulting in sustained skin perfusion in excess of the recovering vasculature of the post-operative skin flap. The 7 day release kinetics bridged the duration of relative skin flap hypoxia until recovery was complete which could improve clinical skin flap viability. Dose delivery curves, systemic effect analysis, larger animal models and use after radiation will provide more information to the clinical applicability of this technology.