# Multiscale models of fibrous interface mechanics

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $474,719

## Abstract

PROJECT SUMMARY
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 global 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:** 10222575
- **Project number:** 5R01AR077793-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Guy M Genin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $474,719
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10222575

## Citation

> US National Institutes of Health, RePORTER application 10222575, Multiscale models of fibrous interface mechanics (5R01AR077793-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10222575. Licensed CC0.

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