# Magneto-patterned cartilage constructs for improved osteochondral integration

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2021 · $46,036

## Abstract

Abstract
Articular cartilage has a poor healing capacity, and so, any damage to the joint surface often progresses to
osteoarthritis (OA), a debilitating joint disease. For patients with symptomatic knee OA, total knee replacement
(TKR) is by far the most common clinical solution. However, TKR is an invasive and end stage procedure, and
there is a growing market for alternate treatments to restore the structure and function of articular cartilage to
ideally prevent OA, or at least delay the time to TKR. While native tissue grafts can be easily press-fit in vivo,
their supply is limited and autologous harvest can lead to pain, motivating tissue engineering (TE) strategies.
To date, most of the work in the field of cartilage TE has focused on producing functional tissues, but has
ignored the integration of these tissues in vivo, limiting the function and durability of cartilage repair. In this
proposal, we seek to engineer cartilage tissues that permit endogenous marrow cell entry in vivo, and
subsequently control the fate of these cells to enhance mineralized matrix deposition between the construct
and underlying bone, ultimately improving construct anchorage. To permit marrow cell infiltration into our
cartilage constructs, a novel magneto-patterning method will be implemented in Aim 1 to mimic the cell
distribution of native cartilage in the engineered constructs. This high-to-low cell distribution will lead to a cell
and matrix-sparse region at the bottom of the constructs, whereby a secondary cell source—the endogenous
marrow cells, can infiltrate. We will create cell gradients in hydrogels using the aforementioned magneto-
patterning approach, which eliminates the need for cell-bound magnetic tags, and instead transiently increases
the magnetic susceptibility of the hydrogel precursor solution to manipulate cell position under a magnetic field.
The magneto-patterned constructs will be cultured in vitro, and we will assess the depth-dependent matrix
accumulation in these cartilage constructs via histological, biochemical, and mechanical measures. To promote
cartilaginous and mineralized matrix interdigitation, we will exploit the force required to press-fit an engineered
construct into a cartilage defect to locally deliver bone-promoting agents (BPAs) at the osteochondral interface.
For this, in Aim 2, magneto-responsive press-activated microcapsules containing BPAs—Triiodothyronine and
β-glycerophosphate—will be patterned in the cell-sparse region of the engineered constructs. Within the cell
laden constructs, the microcapsules will retain their contents throughout the pre-culture period, until they are
press-activated upon in vivo implantation to ensure local `on demand' delivery of the BPAs. Finally, in Aim 3,
the magneto-patterned constructs with opposing populations of mesenchymal stromal cells and press-
activated microcapsules, will be implanted into a minipig trochlear cartilage defect model. Fluorochrome
labeling, micro computed tomog...

## Key facts

- **NIH application ID:** 10140536
- **Project number:** 1F31AR077395-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Hannah Marie Zlotnick
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-02-08 → 2024-02-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140536

## Citation

> US National Institutes of Health, RePORTER application 10140536, Magneto-patterned cartilage constructs for improved osteochondral integration (1F31AR077395-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10140536. Licensed CC0.

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