# Seamless Healing of Avascular Meniscus Tears by Stem Cell Recruitment

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $349,942

## Abstract

Project summary
Meniscus injuries are extremely common with approximately one million patients undergoing treatment
annually in the U.S. alone. Importantly, meniscal disorders inevitably lead to osteoarthritis (OA), which is the
leading cause of disability in this country. As a multiphase fibrocartilage, the outer third of meniscus is a
vascularized and collagen-rich fibrous tissue with fibroblast-like cells, whereas the inner third is avascular
cartilaginous tissue with rounded chondrocyte-like cells. The middle zone is intermediate fibrocartilaginous
tissue with a mixture of fibroblast-like cells and chondrocyte-like cells. Upon injury or defect, the outer zone of
meniscus can reliably be repaired and expected to functionally heal. However, tears in the inner avascular
region are hard to heal due to poor intrinsic healing capacity based on its highly differentiated cell type,
specialized extracellular matrix and lack of blood supply. Despite many attempts to induce functional healing
of avascular meniscus, no therapy currently exists that reliably results in seamless healing of inner-zone
meniscus tears. Although delivery of stem/progenitor cells showed promise for improved avascular meniscus
repair, cell delivery-based approaches have suffered from several translational barriers. Our preliminary study
produced novel data showing that meniscus tears in the avascular zone can be healed by timely controlled
recruitment and step-wise fibrochondrogenic differentiation of synovial mesenchymal stem/progenitor cells
(MSCs). The recruitment and step-wise differentiation was successfully regulated by a single injection of
CTGF-loaded bio-glue mixed with PLGA µS-encapsulating TGFβ3. Accordingly, the overall objective of the
proposed projects is to establish a novel and efficient clinically relevant strategy for seamless healing of
avascular meniscus tears by recruiting endogenous stem/progenitor cells. Our overarching hypothesis is that
temporal control of stem cell recruitment into bio-glue and step-wise fibrocartilaginous differentiation leads to
seamless healing of avascular meniscus tears. We here propose 1) to determine effective compositions of an
injectable and adhesive hydrogel to guide avascular meniscus healing, 2) to determine effective doses and
release rates of growth factors to enhance avascular meniscus healing in vitro, and 3) to enhance avascular
meniscus healing by endogenous stem/progenitor cells in vivo. The expected outcome of the proposed
studies will serve as an important foundation to develop a translational tool to improve treatment for avascular
meniscus tears and defects, thus benefiting millions of patients with meniscus injuries and in turn lowering the
incidence of osteoarthritis.

## Key facts

- **NIH application ID:** 9953949
- **Project number:** 5R01AR071316-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Chang Hun Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $349,942
- **Award type:** 5
- **Project period:** 2017-09-06 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9953949

## Citation

> US National Institutes of Health, RePORTER application 9953949, Seamless Healing of Avascular Meniscus Tears by Stem Cell Recruitment (5R01AR071316-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9953949. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*