ArticlePloS one2019
Graft-implanted, enzyme responsive, tacrolimus-eluting hydrogel enables long-term survival of orthotopic porcine limb vascularized composite allografts: A proof of concept study.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- A systematic review of treatment strategies to combat acute and chronic rejection episodes in vascularized composite allotransplantation.Frontiers in immunology · 2026Pooled it
- Experimental Swine Models for Vascularized Composite Allotransplantation and Immunosuppression: A Systematic Review and Case Report of a Novel Heterotopic Hemifacial Swine Model.Transplant international : official journal of the European Society for Organ Transplantation · 2025Pooled it
- The Transformative Journey of Vascularized Composite Allotransplantation: Advances, Challenges, and Future Directions.Transplantation direct · 2026Article
- A Systematic Review of the Clinical Application of Topical Tacrolimus in Vascularized Composite Allotransplantation.Plastic and reconstructive surgery. Global open · 2026Article
- Systematic review of emerging technologies in vascularized composite allotransplantation.Frontiers in transplantation · 2026Review
- A Precisely Controlled Long-Acting Immunosuppression Platform Enables Prolonged Survival of Vascularized Composite Allografts.bioRxiv : the preprint server for biology · 2025Article
- A mechanically resilient soft hydrogel improves drug delivery for treating post-traumatic osteoarthritis in physically active joints.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Lymph Node Inclusion in a Modified Osteomyocutaneous Allograft for Vascularized Composite Allotransplantation: Establishment and Feasibility Assessment in a Pig Model.Plastic and reconstructive surgery. Global open · 2024Article
- A local drug delivery system prolongs graft survival by dampening T cell infiltration and neutrophil extracellular trap formation in vascularized composite allografts.Frontiers in immunology · 2024Article
- Implantable Immunosuppressant Delivery to Prevent Rejection in Transplantation.International journal of molecular sciences · 2022Review
- Local delivery strategies to restore immune homeostasis in the context of inflammation.Advanced drug delivery reviews · 2021Review
- Local FK506 implants in non-human primates to prevent early acute rejection in vascularized composite allografts.Annals of translational medicine · 2021Article
- Large Animal Models of Vascularized Composite Allotransplantation: A Review of Immune Strategies to Improve Allograft Outcomes.Frontiers in immunology · 2021Review
- Emerging strategies for tissue engineering in vascularized composite allotransplantation: A review.Journal of tissue engineeringReview
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCurrently, patients receiving vascularized composite allotransplantation (VCA) grafts must take long-term systemic immunosuppressive therapy to prevent immunologic rejection. The morbidity and mortality associated with these medications is the single greatest barrier to more patients being able to receive these life-enhancing transplants. In contrast to solid organs, VCA, exemplified by hand or face transplants, allow visual diagnosis of clinical acute rejection (AR), directed biopsy and targeted graft therapies. Local immunosuppression in VCA could reduce systemic drug exposure and limit adverse effects. This proof of concept study evaluated, in a large animal forelimb VCA model, the efficacy and tolerability of a novel graft-implanted enzyme-responsive, tacrolimus (TAC)-eluting hydrogel platform, in achieving long-term graft survival.
methodsOrthotopic forelimb VCA were performed in single haplotype mismatched mini-swine. Controls (n = 2) received no treatment. Two groups received TAC hydrogel: high dose (n = 4, 91 mg TAC) and low dose (n = 4, 49 mg TAC). The goal was to find a dose that was tolerable and resulted in long-term graft survival. Limbs were evaluated for clinical and histopathological signs of AR. TAC levels were measured in serial blood and skin tissue samples. Tolerability of the dose was evaluated by monitoring animal feeding behavior and weight.
resultsControl limbs underwent Banff Grade IV AR by post-operative day six. Low dose TAC hydrogel treatment resulted in long-term graft survival time to onset of Grade IV AR ranging from 56 days to 93 days. High dose TAC hydrogel also resulted in long-term graft survival (24 to 42 days), but was not well tolerated.
conclusionGraft-implanted TAC-loaded hydrogel delays the onset of Grade IV AR of mismatched porcine forelimb VCA grafts, resulting in long term graft survival and demonstrates dose-dependent tolerability.
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