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

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $261,665

## Abstract

ABSTRACT
Rotator cuff tears are common and primarily initiate at the stratified 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 and repair of the structure, composition, and
mechanical performance of the injured tendon-to-bone enthesis using an innovative stratified biomaterial.
Intraoperative 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 and
regenerative activity of bioactive MSCs across the injury site. We will evaluate the design of an innovative
stratified biomaterial to provide mechanical and trophic stimuli to promote MSC retention and enthesis
regeneration. We have generated rigorous proof-of-principle data for a collagen biomaterial that contains bone-
and tendon-mimetic scaffold compartments linked with a continuous hydrogel interface. We will show the
hydrogel interface inhibits strain concentrations that typically form between biomaterials with mismatched
mechanical properties under load. Further, the hydrogel interface provides a site to accelerate fibrocartilage-
like differentiation and remodeling in response to trophic factors produced in adjacent tendon- and bone-
mimetic scaffold compartments. Taken together, we hypothesize inclusion of a continuous hydrogel zone
linking tendon- and bone-specific scaffold compartments provides mechanical and trophic advantages to
accelerate regenerative potency versus monolithic and conventional stratified biomaterials. To address our
hypothesis we will first determine if and how a mechanically-optimized hydrogel insertion both increases
mechanical performance and supports fibrocartilage differentiation in vitro (Aim 1). We will subsequently
demonstrate trophic factors produced across the stratified biomaterial accelerate enthesis-specific MSC
differentiation and matrix remodeling in vitro (Aim 2). We will ultimately evaluate functional repair and
regeneration of the rat rotator cuff enthesis using an enthesis biomaterial-MSC construct in vivo (Aim 3). We
will use in vitro cyclic strain bioreactor studies to optimize MSC-biomaterial interactions, then a tiered set of in
vivo rat rotator cuff injury models to benchmark the quality and kinetics of enthesis regeneration via cellular,
tissue morphology, and mechanical metrics. This project will provide essential insight to aid clinical translation
of a biomaterial therapy to improve musculoskeletal enthesis regeneration.

## Key facts

- **NIH application ID:** 10130723
- **Project number:** 1R01AR077858-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Brendan A. Harley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $261,665
- **Award type:** 1
- **Project period:** 2021-09-27 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130723

## Citation

> US National Institutes of Health, RePORTER application 10130723, Stratified and mechanically-tough biomaterial implant to improve tendon-to-bone enthesis regeneration (1R01AR077858-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10130723. Licensed CC0.

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