Evidence map›Paper›PMID 31497383›Full record

ArticlePeerJ2019

Delivery of targeted gene therapies using a hybrid cryogel-coated prosthetic vascular graft.

Cindy Huynh, Ting-Yu Shih, Alexander Mammoo, Amruta Samant, Saif Pathan, David W Nelson, Christiane Ferran, David Mooney, Frank LoGerfo, Leena Pradhan-Nabzdyk

Abstract read
In one paragraph

Article in PeerJ, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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. Review
  2. Article
  3. Review
  4. Article
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

10 authors.

Cindy HuynhDivision of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.
Ting-Yu ShihJohn A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United States of America.
Alexander MammooDivision of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.
Amruta SamantDivision of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.
Saif PathanBioSurfaces, Inc, Ashland, MA, United States of America.
David W NelsonBioSurfaces, Inc, Ashland, MA, United States of America.
Christiane FerranDivision of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.
David MooneyJohn A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United States of America.
Frank LoGerfo *Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.
Leena Pradhan-Nabzdyk *Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.

Funding

HARVARD-LONGWOOD RESEARCH TRAINING IN VASCULAR SURGERYT32HL007734 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FERRAN, CHRISTIANE, LOGERFO, FRANK W · 1993 to 2023
$10.5M
MECHANISMS OF PROSTHETIC ARTERIAL GRAFT FAILURER01HL021796 · NHLBI · NEW ENGLAND DEACONESS HOSPITAL · PI FERRAN, CHRISTIANE, LOGERFO, FRANK W · 1987 to 2020
$9.0M
Genetic Engineering of Vein Bypass Grafts in Vascular and Cardiovascular SurgeryR01HL086741 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BHASIN, MANOJ, FERRAN, CHRISTIANE · 2007 to 2022
$7.4M
Harvard-Longwood Short-Term Research Training in Vascular SurgeryT35HL110843 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI CHRISTIANE FERRAN, FRANK W LOGERFO · 2013 to 2026
$609k
Bioengineering of vein grafts to resist intimal hyperplasiaR21EB024308 · NIBIB · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FERRAN, CHRISTIANE · 2018 to 2019
$481k
NHLBI NIH HHS R01 HL021796NHLBI NIH HHS R01 HL086741NHLBI NIH HHS T32 HL007734NHLBI NIH HHS T35 HL110843NIBIB NIH HHS R21 EB024308
6 · The paper itself

Abstract

objectivesThe success of prosthetic vascular grafts in the management of peripheral arterial disease is frequently limited by the development of anastomotic neointimal hyperplasia (ANIH), with the host response to prosthetic grafts beginning soon after implantation. To address this, we combine a platform of polyethylene terephthalate (PET) fabric with an applied cryogel layer containing biologic agents to create a bioactive prosthetic graft system, with the ability to deliver therapeutics targeting modulators of the ANIH-associated transcriptome response, along with antithrombotic agents.

methodsHybrid graft materials were synthesized by cryopolymerization of methacrylated alginate and heparin onto electrospun (ePET), knitted PET (kPET), or woven PET (wPET). Arg-Gly-Asp (RGD) peptides were added to increase cell adhesion. Scanning electron microscopy (SEM) was used to study the microstructure at 1 day, and 2, 4, and 8 weeks. Physical properties such as swelling ratio, pore connectivity, shape recovery, and stiffness were evaluated. Human aortic endothelial cell (HAoEC) adherence was visualized using confocal microscopy after 24 hours and proliferation was evaluated with a resazurin-based assay for 7 days. Confocal microscopy was used to assess delivery of adeno-associated virus (AAV-GFP) after incubation of hybrid grafts with HAoECs. Heparin activity of the materials was measured using an anti-Xa assay.

resultsSEM demonstrated large interconnected pores throughout the entire structure for all graft types, with minimal degradation of the cryogel after 8 weeks. Hybrid materials showed a trend towards increased shape recovery, increased stiffness, decreased swelling ratio, and no difference in pore connectivity. HAoECs incorporated, adhered, and proliferated over 7 days on all materials. HAoECs were successfully transduced with AAV-GFP from the hybrid graft materials. Anti-Xa assay confirmed continued activity of heparin from all materials for over 7 days.

conclusionsWe have developed a bioactive prosthetic graft system with a cryogel coating capable of delivering biologic agents with antithrombotic activity. By applying the cryogel and selected agents onto PET prior to graft implantation, this study sets the stage for the system to be individualized and tailored to the patient, with bioengineering and targeted gene therapy strategies dovetailing to create an improved prosthetic graft adaptable to emerging knowledge and technologies.

Indexed as

BiomaterialsCryogelIntimal hyperplasiaPeripheral arterial diseasePolymerProsthetic graft materialVascular surgery

Identifiers

PMID31497383
PMCPMC6707340

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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.