# Regenerating Hyaline Cartilage Using Nanofibrous Hollow Microspheres and Synergizing TGF-beta and HIF

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $264,275

## Abstract

Traumatized and diseased joint cartilage is the leading cause of disability, afflicting 33% of the adult
population. State-of-the-art treatments for destroyed joint cartilage are seriously limited. Tissue engineering
has this far failed to regenerate high-quality cartilage and prevent subsequent cartilage hypertrophy and
degeneration. We have developed biodegradable nanofibrous hollow microspheres (NF-HMS) as a novel
injectable carrier for chondrocytes and successfully regenerated high-quality cartilage. To circumvent both
the shortage of autologous chondrocytes and the regulatory barriers to cell-based therapies, we propose to
regenerate cartilage and suppress hypertrophy and degeneration by injecting the novel NF-HMS
microcarrier that delivers key biological molecules to activate endogenous bone marrow stromal cells
(BMSCs) for hyaline cartilage regeneration and suppress. First, we will mechanistically determine whether
HIF-1, HIF-2, or both promote chondrogenesis and prevent hypertrophy/degeneration. Second, we will
develop TGF- and the HIF stabilizer releasing NF-HMS to facilitate the chondrogenic differentiation of
human and rabbit BMSCs using in vitro and a subcutaneous implantation model. Third, we will use the novel
injectable NF-HMS carrier to synergize TGF- and HIF activities of endogenous BMSCs in order to
regenerate and maintain high-quality cartilage in a rabbit osteochondral repair model. By accomplishing
these specific aims, we will substantially deepen our understanding of the key factors that affect
chondrogenesis, cartilage regeneration, and prevention of hypertrophy and cartilage degeneration, leading
to a novel cartilage repair therapy without using exogenous or exogenously manipulated cells. The
understandings and strategies developed in this project can also be utilized to engineer other tissues.
1

## Key facts

- **NIH application ID:** 10268987
- **Project number:** 5R01AR075770-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** PETER X MA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $264,275
- **Award type:** 5
- **Project period:** 2020-09-23 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10268987

## Citation

> US National Institutes of Health, RePORTER application 10268987, Regenerating Hyaline Cartilage Using Nanofibrous Hollow Microspheres and Synergizing TGF-beta and HIF (5R01AR075770-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10268987. Licensed CC0.

---

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