Evidence map›Paper›PMID 35915321›Full record

ArticlePharmaceutical research2022

Tacrolimus-Eluting Disk within the Allograft Enables Vascularized Composite Allograft Survival with Site-Specific Immunosuppression without Systemic Toxicity.

Firuz G Feturi, Jignesh V Unadkat, Wensheng Zhang, Mohamed El Hag, Yong Wang, Chiaki Komatsu, Damian Grybowski, Zhaoxiang Zhang, Vasil Erbas, Huseyin Sahin and 8 more

Abstract read
PubMed Publisher
In one paragraph

Article in Pharmaceutical research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Hand transplantation: can we balance the risks and benefits?The Journal of hand surgery, European volume · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 3 countries.

Firuz G FeturiDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 7220 Salk Hall, 3501 Terrace Street, Pittsburgh, PA, 15261, USA.
Jignesh V UnadkatDepartment of Plastic and Reconstructive Surgery, School of Medicine, University of Pittsburgh, Scaife Hall, Suite 6B, 3550 Terrace Street, Scaife Hall, Suite 6B, Pittsburgh, PA, 15261, USA.
Wensheng ZhangDepartment of Plastic and Reconstructive Surgery, School of Medicine, University of Pittsburgh, Scaife Hall, Suite 6B, 3550 Terrace Street, Scaife Hall, Suite 6B, Pittsburgh, PA, 15261, USA.
Mohamed El HagDepartment of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Yong WangDepartment of Plastic and Reconstructive Surgery, School of Medicine, University of Pittsburgh, Scaife Hall, Suite 6B, 3550 Terrace Street, Scaife Hall, Suite 6B, Pittsburgh, PA, 15261, USA.
Chiaki KomatsuDepartment of Plastic and Reconstructive Surgery, School of Medicine, University of Pittsburgh, Scaife Hall, Suite 6B, 3550 Terrace Street, Scaife Hall, Suite 6B, Pittsburgh, PA, 15261, USA.
Damian GrybowskiDepartment of Plastic and Reconstructive Surgery, School of Medicine, University of Pittsburgh, Scaife Hall, Suite 6B, 3550 Terrace Street, Scaife Hall, Suite 6B, Pittsburgh, PA, 15261, USA.
Zhaoxiang ZhangDepartment of Plastic and Reconstructive Surgery, School of Medicine, University of Pittsburgh, Scaife Hall, Suite 6B, 3550 Terrace Street, Scaife Hall, Suite 6B, Pittsburgh, PA, 15261, USA.
Vasil ErbasDepartment of Plastic, Reconstructive and Aesthetic Surgery, Medical Park Gaziantep Hospital, Gaziantep, Turkey.
Huseyin SahinPrivate Cagsu Hospital, Duzce, Turkey.
Sean McclaineDepartment of Plastic and Reconstructive Surgery, School of Medicine, University of Pittsburgh, Scaife Hall, Suite 6B, 3550 Terrace Street, Scaife Hall, Suite 6B, Pittsburgh, PA, 15261, USA.
Sinan OksuzDepartment of Plastic, Reconstructive and Aesthetic Surgery, School of Medicine, Gulhane Military Medical Academy, Ankara, Turkey.
Jan PlockDivision of Plastic and Hand Surgery, University Hospital Zurich, Zurich, Switzerland.
Vijay S GorantlaDepartments of Surgery, Ophthalmology and Bioengineering, Wake Forest School of Medicine, Wake Forest Institute of Regenerative Medicine, Winston Salem, NC, USA.
Kia M WashingtonDepartment of Plastic and Reconstructive Surgery, School of Medicine, University of Pittsburgh, Scaife Hall, Suite 6B, 3550 Terrace Street, Scaife Hall, Suite 6B, Pittsburgh, PA, 15261, USA.
Mario G SolariDepartment of Plastic and Reconstructive Surgery, School of Medicine, University of Pittsburgh, Scaife Hall, Suite 6B, 3550 Terrace Street, Scaife Hall, Suite 6B, Pittsburgh, PA, 15261, USA.
Raman Venkataramanan *Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 7220 Salk Hall, 3501 Terrace Street, Pittsburgh, PA, 15261, USA. rv@pitt.edu.
Alexander M Spiess *Department of Plastic and Reconstructive Surgery, School of Medicine, University of Pittsburgh, Scaife Hall, Suite 6B, 3550 Terrace Street, Scaife Hall, Suite 6B, Pittsburgh, PA, 15261, USA. spiessam@upmc.edu.
University of Pittsburgh · USMedical Park Gaziantep Hospital · TRTurkish Armed Forces · TRUniversity Hospital of Zurich · CHWake Forest University · US

Funding

Department of Plastic and Reconstructive Surgery and Department of Pharmaceutical Sciences, University of Pittsburgh xxxxx
6 · The paper itself

Abstract

aimWidespread clinical application of vascularized composite allotransplantation (VCA) has been limited by the need for lifelong systemic immunosuppression to prevent rejection. Our goal was to develop a site-specific immunosuppressive strategy that promotes VCA allograft survival and minimizes the risk of systemic side effects.

methodsTacrolimus loaded polycaprolactone (TAC-PCL) disks were prepared and tested for their efficacy in sustaining VCA allograft survival via site-specific immunosuppression. Brown Norway-to-Lewis rat hind limb transplantations were performed; animals received one TAC disk either in the transplanted (DTx) or in the contralateral non-transplanted (DnonTx) limbs. In another group, animals received DTx and lymphadenectomy on Tx side. Blood and allograft levels of TAC were measured using LC-MS/MS. Systemic toxicity was evaluated.

resultsAnimals that received DTx achieved long-term allograft survival (> 200 days) without signs of metabolic and infectious complications. In these animals, TAC blood levels were low but stable between 2 to 5 ng/mL for nearly 100 days. High concentrations of TAC were achieved in the allografts and the draining lymph nodes (DLN). Animals that underwent lymphadenectomy rejected their allograft by 175 days. Animals that received DnonTx rejected their allografts by day 70.

conclusionControlled delivery of TAC directly within the allograft (with a single TAC disk) effectively inhibits rejection and prolongs VCA allograft survival, while mitigating the complications of systemic immunosuppression. There was a survival benefit of delivering TAC within the allograft as compared to a remote site. We believe this approach of local drug delivery has significant implications for drug administration in transplantation.

Indexed as

Composite Tissue AllograftsTacrolimusAllograftsAnimalsChromatography, LiquidGraft SurvivalImmunosuppression TherapyImmunosuppressive AgentsRatsRats, Inbred BNRats, Inbred LewTandem Mass SpectrometryImmunosuppressive AgentsTacrolimusdrug-eluting biomaterialsrejectionsite specific immunosuppressiontacrolimusvascularized composite allografts

Identifiers

PMID35915321
OpenAlexW4289333458

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.