# Cell Cycle-Mediated Optimization of Cartilage Tissue Development

> **NIH NIH R21** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $137,110

## Abstract

PROJECT SUMMARY
 An estimated 27 million Americans age ≥25 have osteoarthritis (OA) and this number is projected to
escalate to more than 65 million by 2029 at a direct cost estimated at $28.6 billion. Reducing the incidence and
effects of OA through effective treatment of cartilage defects would be a significant socioeconomic benefit. As
the supply of suitable cartilage grafts is unable to meet clinical demand, the development of tissue engineered
osteochondral grafts with mechanically functional properties would have a significant clinical impact.
 Examination of engineered cartilage tissues at a multi-scale level suggests local variable ECM content
at the single cell level, where cells, for example, exhibiting intense metachromatic staining for ECM are
juxtaposed to others with relatively little metachromatic staining. We speculate that this intrinsic cell-to-cell
variability in ECM production capacity undermines or limits the peak tissue properties attainable by the whole
cell population, and may also impact engineered cartilage integrative repair potential.
 This proposal will test the following hypotheses: H1) Cell cycle priming leads to coordinated cell tissue
elaboration capacity, thereby expediting development and peak magnitude of functional tissue properties by
decreasing local spatial inhomogeneity in engineered cartilage derived from clinically-relevant chondrocytes.
H2) Cell cycle priming is mediated in part by primary cilia that increase in incidence post synchronization. H3)
Repair of full thickness osteochondral defects with engineered cartilage constructs derived from initially (cell
cycle) synchronized chondrocytes will be superior to non-synchronized (control) chondrocytes due to the
unprecedented acceleration of functional tissue development associated with cell cycle priming that leads to
cartilage grafts that better approximate the cartilage associated with clinical osteochondral allografts.
 The corresponding aims will study human and canine chondrocytes in vitro (Specific Aim 1) and
engineered canine cartilage constructs in vivo with a full-thickness ostechondral focal defect repair model in
the dog (Specific Aim 2).
 This NIH R21 application will explore the potential for cell cycle priming as a novel platform technology
for functional tissue engineering and generation of tissues with native mechanical properties in 6 weeks or
less. We will determine if the functional benefits of cell synchronization on 3D cartilage tissue formation are
derived from the reduction of cell-to-cell variability and homogenization of cell ECM output. While the concept
of cell synchronization is well-established in cell biology, its application for engineering cartilage, as
demonstrated by our preliminary data, represents an innovation.

## Key facts

- **NIH application ID:** 9896522
- **Project number:** 1R21AR075245-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Clark T. Hung
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $137,110
- **Award type:** 1
- **Project period:** 2020-03-19 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896522

## Citation

> US National Institutes of Health, RePORTER application 9896522, Cell Cycle-Mediated Optimization of Cartilage Tissue Development (1R21AR075245-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9896522. Licensed CC0.

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