# Lower Extremity Bypass Graft With Physiologic Longitudinal Pre-Stretch

> **NIH NIH P20** · UNIVERSITY OF NEBRASKA OMAHA · 2024 · $240,732

## Abstract

PROJECT SUMMARY – Lower Extremity Bypass Graft With Physiologic Longitudinal Pre-Stretch
Despite years of improvements and refinements in technologies and pharmacological adjuncts, failure rates
remain high for lower extremity prosthetic grafts, particularly when grafts cross the knee joint. Though much work
has been done focusing on pathological processes associated with infrainguinal synthetic graft failure, the
underlying mechanisms remain incompletely understood. The main artery of the lower extremity, the
femoropopliteal artery (FPA), demonstrates significantly different structural features and mechanical properties
compared to other arteries. The specialized arrangement of its extracellular matrix components creates
longitudinal tension, also known as longitudinal pre-stretch (LPS). In young arteries that are pre-stretched in situ
like a rubber band under tension, LPS prevents arterial buckling during limb movement, but in older FPAs, LPS
is significantly reduced, which results in more severe bending, kinking, high intramural stresses, and disturbed
flow in the bent limb, promoting deleterious cellular and biochemical responses that may culminate in both
primary disease development and reconstruction failure. While reduced LPS in PAD patients likely cannot be
restored, it can be engineered into bypass grafts used to treat them. We have developed a method of
manufacturing nanofibrillar elastomeric bypass (NEB) graft fabrics with nonlinear compliance that can be tuned
to match that of blood vessels. By electrospinning biomedical grade elastomers, we made fabrics that can
produce low resistance to physiological deformations while protecting the material from overstretching at
elevated loads. Our preliminary data using a swine model demonstrate that the NEB graft fabric maintains its
compliance, undergoes rapid endothelialization, and gets quickly incorporated into the arterial wall. In this
application, we propose to decouple longitudinal and circumferential compliances of our material to fully mimic
the complexity of human FPA biomechanics, and test the hypothesis that FPA-tuned NEB grafts with LPS
produce less tortuosity, improved hemodynamics, and better in vivo healing responses compared with
grafts without LPS. This hypothesis will be tested through three specific aims, whereby we will first optimize
the manufacturing method and develop an empirical framework for making compliant anisotropic grafts. Second,
we will develop NEB grafts tuned to healthy human FPAs and test them for their mechanical properties, suture
retention, water permeability, burst strength, cytotoxicity, platelet adhesion characteristics, implantability,
biomechanics, and flow characteristics using in silico and in vitro methods. Lastly, we will test the performance
of pre-stretched and non-pre-stretched NEB grafts in a preclinical swine model. This project will demonstrate
whether incorporating LPS into lower extremity bypass grafts to reduce bending and tortuosity of...

## Key facts

- **NIH application ID:** 10770980
- **Project number:** 1P20GM152301-01
- **Recipient organization:** UNIVERSITY OF NEBRASKA OMAHA
- **Principal Investigator:** Kaspars Maleckis
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $240,732
- **Award type:** 1
- **Project period:** 2024-02-15 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10770980

## Citation

> US National Institutes of Health, RePORTER application 10770980, Lower Extremity Bypass Graft With Physiologic Longitudinal Pre-Stretch (1P20GM152301-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10770980. Licensed CC0.

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