# Stratified and mechanically-tough biomaterial implant to improve tendon-to-bone enthesis regeneration

> **NIH NIH R56** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $382,265

## Abstract

ABSTRACT
Rotator cuff tears are common and occur most commonly as partial-width injuries within the fibrocartilage
interface (enthesis) linking tendon to bone. Surgical reattachment of tendon to bone forms a narrow
fibrovascular scar rather than regenerates a continuous fibrocartilage enthesis. The resultant sharp boundary
between mechanically mismatched tendon and bone leads to strain concentrations and high rates of re-failure
at the enthesis. The objective of this proposal is to guide functional regeneration of the structure, composition,
and mechanical performance of the injured tendon-to-bone enthesis using an innovative biomaterial therapy.
Local implantation of MSCs at the injury site during surgical repair is an attractive option to accelerate enthesis
regeneration. However it is essential to develop a biomaterial carrier to improve retention of bioactive MSCs at
the injury site and to provide an optimized microenvironment to spatially-regulate MSC differentiation and
fibrocartilage remodeling. We have generated rigorous proof-of-principle data for an innovative biomaterial that
contains porous mineralized (bone) and anisotropic (tendon) scaffold compartments linked with a continuous
gelatin hydrogel interface. This hydrogel interface inhibits formation of strain concentrations that typically form
between biomaterials with mismatched mechanical properties under load. The hydrogel interface also provides
a depot to locally pattern morphogens to accelerate MSC fibrocartilage differentiation and matrix remodeling.
To address our objective we will first demonstrate a mechanically-optimized hydrogel insertion increases
biomaterial toughness and locally promotes fibrocartilage differentiation. We will subsequently establish a
fibrocartilage-optimized biomolecule patterning strategy to accelerate enthesis-specific MSC differentiation and
matrix remodeling. We will ultimately evaluate functional regeneration of the rat rotator cuff enthesis using an
optimized biomaterial-MSC construct. We will use in vitro cyclic strain bioreactor studies to optimize MSC-
biomaterial interactions as well as a rigorous in vivo rat rotator cuff injury model to benchmark the quality and
kinetics of enthesis regeneration via cellular, tissue morphology, and mechanical metrics. This project
addresses critical gaps in knowledge and will validate an innovative biomaterial paradigm to accelerate
musculoskeletal enthesis regeneration.

## Key facts

- **NIH application ID:** 10250667
- **Project number:** 1R56AR077858-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Brendan A. Harley
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,265
- **Award type:** 1
- **Project period:** 2020-09-18 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10250667

## Citation

> US National Institutes of Health, RePORTER application 10250667, Stratified and mechanically-tough biomaterial implant to improve tendon-to-bone enthesis regeneration (1R56AR077858-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10250667. Licensed CC0.

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