# Multiscale models of fibrous interface mechanics

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $101,277

## Abstract

PROJECT SUMMARY
From parent grant: Interfaces between tissues either transfer load (requiring toughness) or provide a smooth
surface (requiring low friction). Fibrous interfaces are very effective at transferring load between tissues, e.g., at
connective tissue-bone interfaces (“entheses”), peritoneal-mesentery interfaces, interfaces between layers of
the vasculature, and the pia mater. These interfaces require toughness to resist high stresses associated with
material mismatches. Surgical repair can lead to smooth interfaces becoming fibrous, (e.g., following hernia
surgery) or to tough interfaces becoming weak (e.g., following tendon- and ligament-to-bone repair). In older
patients with large rotator cuff repairs, for example, where the desired attachment is not reformed, up to 94% of
surgical repairs fail. These challenges arise in part because the features that endow fibrous interfaces with
toughness are not known. We therefore propose to develop a comprehensive modeling and experimental
approach for studying the factors underlying the transition from tough to weak in a fibrous interface. Our previous
work motivates the hypothesis that disorder is a key toughening feature of fibrous attachments. We will focus
initially on the example of tendon attaching to bone, in which microscale disorder underlies the ordered
macroscale, graded transition between the two tissues, as a foundation for studying the general problem of
adhesion throughout the body. We predict that disorder enhances energy absorption by distributing failure
processes and energy absorption over larger volumes of tissue. We propose this as a fundamental mechanism
by which fibrous interfaces in the body transfer load effectively. We will test these ideas through two aims:
(1) Identify and model the mechanisms of fibrous attachment toughening ex vivo. We will model and
experimentally validate how disorder across length scales toughens the tendon-to-bone attachment. Hierarchical
molecular dynamics-to-continuum models, enriched by machine learning, will be validated in vitro, in systems
with nanoscale control of mineral distributions, and ex vivo, in tissue samples of fibrous attachments. (2) Identify
and model the loss of fibrous attachment toughness due to pathologic settings in vivo using murine rotator cuff
tendinopathy models. In both aims, nano- through milli-scale characterization will be performed to define the
mechanisms driving mechanical behavior. We will test the hypothesis that pathology-induced changes at
multiple length scales will predict changes in failure mode. These models and experiments will test the hypothesis
that energy absorption across hierarchies is a fundamental toughening mechanism by which fibrous interfaces
resist injury level loads. Taken together, we believe that these new models of fibrous attachment will enable an
understanding of how the order and complexity of fibrous attachments leads to effective attachment of tissues.

## Key facts

- **NIH application ID:** 10601609
- **Project number:** 3R01AR077793-03S1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Guy M Genin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $101,277
- **Award type:** 3
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10601609

## Citation

> US National Institutes of Health, RePORTER application 10601609, Multiscale models of fibrous interface mechanics (3R01AR077793-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10601609. Licensed CC0.

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