TNP-470 reduces collagen and macrophage accumulation in expanded polytetrafluoroethylene tube implants

TNP-470 is a potent angiogenic inhibitor that has been demonstrated to decrease the rate of cutaneous wound healing. This study investigated the effect that TNP-470 has upon collagen growth and macrophage infiltration into expanded polytetrafluoroethylene (e-PTFE) tube implants.

e-PTFE tubes (1.0 cm in length) were implanted into the dorsum of male Swiss-Webster mice (8-10 weeks old). TNP-470 was administered subcutaneously in doses of 0.5, 1.0, or 5.0 mg/kg for determination of hydroxyproline accumulation on day 18 after implantation. Additionally, TNP-470 was administered at 5.0 mg/kg for determination of macrophage infiltration on days 4, 8, 13, and 18 after implantation.

Administration of TNP-470 at doses of 1.0 and 5.0 mg/kg on days 0, 2, and 4 significantly (P < 0.05) decreased hydroxyproline accumulation in e-PTFE implants on day 18 after implantation. Administration of 0.5 mg/kg of TNP-470 yielded no significant difference vs the vehicle control (P < 0.81). Additionally, administration of TNP-470 at 5.0 mg/kg on days 0, 2, and 4 significantly (P < 0.05) decreased macrophage infiltration into e-PTFE implants on day 4 after implantation. There was also a significantly (P < 0.05) increased percentage of macrophages in the e-PTFE implants on day 13 after wounding. No significant differences were observed between the experimental and control groups on days 8 and 18.

Administration of TNP-470 significantly decreases hydroxyproline accumulation in e-PTFE implants. These data suggest that while TNP-470 is administered, macrophage infiltration is impaired; however, upon discontinuing administration, macrophage infiltration increases. Possible mechanisms to account for these findings are discussed.