Enoxaparin does not affect network formation of adipose tissue-derived microvascular fragments

Dermal substitutes are frequently used for the initial coverage of extensive skin defects. The seeding of these implants with adipose tissue-derived microvascular fragments (ad-MVF) has recently been shown to accelerate their vascularization and incorporation. In the present study we analyzed whether these processes are affected by a thromboprophylactic therapy with the low molecular weight heparin (LMWH) enoxaparin (enox). Green fluorescent protein (GFP)⁺ ad-MVF were isolated from enox- (8 mg/kg s.c.) and vehicle-treated (0.9% NaCl s.c.) (C57BL/6-Tg(CAG-EGFP)1Osb/J mice and seeded onto Integra matrices. Subsequently, these were implanted into full-thickness skin defects within dorsal skinfold chambers of enox- and vehicle-treated C57BL/6 wild-type mice. Repetitive stereomicroscopy and intravital fluorescence microscopy over 2 weeks as well as histological and immunohistochemical analyses on day 14 revealed that enox does not inhibit the reassembly of ad-MVF into new microvascular networks. In addition, treatment with the anticoagulative compound did not promote implant-induced hemorrhage formation. Accordingly, Integra matrices in enox- and vehicle-treated animals exhibited a comparable final microvessel density, fraction of GFP⁺ blood vessels originating from seeded ad-MVF, collagen fiber content, and epithelialization. These novel findings demonstrate that the seeding of dermal substitutes with ad-MVF may be applied also during thromboprophylactic therapy without affecting implant vascularization and bleeding risk.