# Incorporation of Dexamethasone Delivery within Engineered Cartilage

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $475,156

## Abstract

PROJECT SUMMARY
 The ability to resurface larger defects (>2cm2 up to a hemicondyle) with mature hyaline articular
cartilage and address the underlying bone deficit in a single procedure makes osteochondral allograft
transplantation an attractive option. The appropriate size and surface contour can be matched when the graft is
obtained from an appropriately selected organ donor. Mature chondrocytes can survive for many years post-
transplantation without immunosuppressive therapy. As there is insufficient supply of suitable cartilage grafts to
meet the clinical demand, the development of tissue engineered osteochondral grafts and strategies to
promote their successful application in the joint would have significant clinical impact for treatment of localized
cartilage lesions (of focus in this proposal) and whole joint surfaces (to be addressed in the future).
 Data from animal studies and early clinical trials suggest that early inhibition of the intra-articular
inflammatory response (e.g., 4 weeks) posttraumatic injury of the knee may improve clinical outcomes.
Research from our team portrays dexamethasone (dex), a synthetic glucocorticoid that has pro-anabolic and
anti-catabolic effects in cartilage tissue engineering systems, as a critical element for cultivating cartilage
tissues with native properties, as well as for providing chondroprotection to inflammatory cytokines. As these
factors are likely to impact the clinical success of cartilage tissue engineering strategies, and dex is FDA-
approved and used clinically to reduce pain and inflammation, we sought to develop a strategy to make these
tissue culture findings more clinically relevant. From our perspective, an ideal method would retain the benefits
of dex on engineered cartilage without the requirement for its exogenous supplementation, as clinical injections
of steroids in the joint have been associated with negative side effects.
 In this new R01 grant, we propose the incorporation of dex-supplemented, poly(lactide-co-glycolide)
(PLGA) microspheres into cell-seeded hydrogel constructs as a means for dex delivery from within engineered
cartilage. We present preliminary data demonstrating that dex release internally from PLGA microspheres
incorporated in chondrocyte-seeded hydrogel constructs promotes growth of mechanically functional cartilage
tissue and confers cytokine protection in a manner akin to that observed with dex externally supplemented in
culture media. In vivo efficacy of dex-microspheres has been confirmed by our team for adipose tissue
engineering applications. With localized dex delivery, these benefits were achievable using concentrations that
are orders of magnitude lower than adopted for clinical administration by injection. To build on this promising
finding and to further realize the potential for clinical translation of this strategy for cell-based cartilage repair,
we pose the following global hypothesis: Incorporation of polymer microspheres that release dex f...

## Key facts

- **NIH application ID:** 10130376
- **Project number:** 5R01AR068133-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Clark T. Hung
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $475,156
- **Award type:** 5
- **Project period:** 2016-05-16 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130376

## Citation

> US National Institutes of Health, RePORTER application 10130376, Incorporation of Dexamethasone Delivery within Engineered Cartilage (5R01AR068133-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10130376. Licensed CC0.

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