# Preclinical optimization and design for manufacturability of immunoregulatory tissue-engineered vascular grafts

> **NIH NIH R61** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $389,314

## Abstract

SUMMARY
 Despite the emergence of a few companies in recent years based on the clinical translation of small diameter
tissue-engineered vascular grafts (TEVGs), the gold standard for arterial bypass in the clinic continues to be
autologous vein or artery grafts. Our group has developed, with previous NIH funding, TEVGs based on the
documented pro-regenerative immunoregulatory potency of mesenchymal stem/stromal cells (MSCs) and
tubular, biodegradable scaffolds. MSCs are immunoregulatory in that they both recruit host neutrophils and
macrophages via secreted factors and modulate the recruited cells to a tolerant and pro-regenerative phenotype.
We have also demonstrated that MSCs can stimulate the production of new functional vascular extracellular
matrix both in-vitro and in-vivo and that MSCs play an acute antithrombogenic role in our TEVGs.
 Our published work has rigorously tested the ability of human-derived MSCs to induce remodeling of TEVG
constructs when implanted as rat aortic interposition grafts. In very recent unpublished work (embargoed pending
IP protection), we have also successfully tested in the same rat model cell-free TEVG strategies based on
immunoregulatory factors secreted by MSCs. These have included the use of cytokine- and MSC secreted
factor-loaded microspheres and MSC-derived extracellular vesicles (EVs) loaded into TEVG scaffolds.
 We define our TEVG strategies in terms of feasible combinations of “payload” (MSCs, cytokine-loaded
microspheres, MSC secreted factor-loaded microspheres, and MSC-derived EVs) loaded into three different
types of scaffolds (poly(ester urethane)urea (PEUU), lyophilized silk fibroin (LyoGel), and bilayered porous silk).
We have also begun to scale-up the fabrication processes of these TEVG configurations in anticipation of
eventual large animal testing and have demonstrated success with a sheep implant pilot study in anticipation of
this proposal submission.
 Our proposed milestone-driven project is ideal for this two-phase Catalyze grant mechanism and successful
completion will lead to significant progress toward the clinical translation of our TEVG technology. The R61
phase has two objectives with milestones that will allow us to fully evaluate, in our well-established and relatively
high-throughput rat model, all feasible TEVG configurations. The primary outcome of the R61 Phase will be to
identify the best combination(s) of immunoregulatory payload and scaffold for a TEVG construct that can most
optimally remodel in-vivo into a native-like artery. The R33 phase has five objectives with milestones that will
first demonstrate successful fabrication of scaled-up versions of the TEVG configurations that meet the
milestones of the R61 phase, and then perform large animal testing of the best (up to four) configuration(s). The
outcome of this phase will be to identify the optimal TEVG configuration to move forward toward clinical testing
and commercialization, and also to address design for manufac...

## Key facts

- **NIH application ID:** 10234197
- **Project number:** 5R61HL154102-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** David Alan Vorp
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $389,314
- **Award type:** 5
- **Project period:** 2020-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234197

## Citation

> US National Institutes of Health, RePORTER application 10234197, Preclinical optimization and design for manufacturability of immunoregulatory tissue-engineered vascular grafts (5R61HL154102-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10234197. Licensed CC0.

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