There is still unmet demand for effective, safe, and patient-friendly anti-thrombotics to treat deep vein thrombosis (DVT) during pregnancy. Here we first engineer a bioactive amphiphile (TLH) by simultaneously conjugating Tempol and linoleic acid onto low molecular weight heparin (LMWH), which can assemble into multifunctional nanoparticles (TLH NP). In pregnant rats with DVT, TLH NP can target and dissolve thrombi, recanalize vessel occlusion, and eradicate the recurrence of thromboembolism, thereby reversing DVT-mediated intrauterine growth restriction and delayed development of fetuses. Mechanistically, therapeutic effects of TLH NP are realized by inhibiting platelet aggregation, facilitating thrombolysis, reducing local inflammation, attenuating oxidative stress, promoting endothelial repair, and increasing bioavailability. By decorating with a fibrin-binding peptide, targeting efficiency and therapeutic benefits of TLH NP are considerably improved. Importantly, LMWH nanotherapies show no toxicities to the mother and fetus at the dose 10-time higher than the examined therapeutic dosage.
© 2022. The Author(s).

The use of topical immunosuppressants has been anecdotally reported for the treatment of rejection in vascularized composite allotransplantation. The aim of this study was to evaluate the effectiveness of topical tacrolimus and clobetasol in the prevention and treatment of rejection.
Seventy-six hemiface allotransplants, between ACI (RT1) donors and Lewis (RT1) recipients, were performed in 11 groups and treated with topical tacrolimus or clobetasol, or in combination with systemic cyclosporine A and anti-αβ-T-cell receptor antibody for 1 week. Topical treatment increased the survival of the allograft in all groups.
Best outcomes were obtained in the groups treated with systemic therapy and topical tacrolimus. Expression of proinflammatory cytokines interleukin 2, interferon γ, tumor necrosis factor α, and transforming growth factor β correlated with clinical signs of rejection and the final outcomes. Clobetasol application was associated with a marked depletion of lymphocytic populations, and dermal and epidermal atrophy.
Both topical tacrolimus and clobetasol were effective in treating episodes of acute rejection, and the best outcomes were achieved when their application was initiated after systemic immunosuppression. Topical tacrolimus proved to be a preferable adjunct agent to the systemic therapy by preventing both the local and systemic complications.