# Engineering biomimetic knee menisci with zonal and anisotropic variations

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $434,621

## Abstract

PROJECT SUMMARY
This proposal aims to tissue engineer an anisotropic neo-meniscus that also captures the regional variations
present in the native tissue. Subsequently, allogeneic neo-meniscal constructs will be implanted in a leporine
model to achieve both meniscus repair and replacement. It is hypothesized that: 1) regionally variant,
anisotropic, meniscus-shaped constructs can be engineered by optimizing cell culture and scaffold-free culture
conditions; 2) the strategic temporal application of multi-level stimuli (at cellular-, molecular-, and construct-
levels) will allow for synergisms across the different levels of action to enhance the functional properties of the
maturing neo-menisci; and 3) allogeneic constructs can be successfully implanted in a leporine model. These
hypotheses will be tested via the following three specific aims: 1) To create an anisotropic neo-meniscus with
regional variations mimicking native tissue; 2) to enhance functional and organizational properties of the neo-
meniscus via multi-level exogenous stimulation synergized by temporal coordination; and 3) to develop
surgical fixation techniques and implant the neo-menisci in the rabbit. Previously, the native meniscus was
found to be highly anisotropic and regionally variant both morphologically and biomechanically, motivating our
current tissue engineering approach to mimic these characteristics. Allogeneic leporine cells will be used to
form organizationally and regionally mimetic neo-meniscal constructs in Aim 1; this goal will be accomplished
via the use of novel spatial and temporally variant seeding techniques. The anisotropic and organizational
properties of the engineered neo-meniscus will then be enhanced by manipulating molecular-, cellular-, and
construct-level targets in Aim 2. Specifically, TGF-β1 and hydrostatic pressure will act on the cellular level to
increase matrix production; lysophosphatidic acid and chondroitinase-ABC will be used to align and compact
the matrix at the molecular level; and meniscus-specific mechanical stimulation will direct anisotropy at the
construct level. In this proposal, to avoid the use of primary cells, we will investigate the use of passaged
allogeneic cells toward in vivo repair and replacement of the meniscus (Aim 3). Upon successful demonstration
of repair/replacement in the leporine model, we will determine methods to likewise expand sheep and human
cells for future studies. This approach seeks to address the issue of tissue scarcity and aims to provide a
solution to the complex problem of meniscus repair and replacement.

## Key facts

- **NIH application ID:** 9953950
- **Project number:** 5R01AR071457-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Kyriacos A Athanasiou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $434,621
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9953950

## Citation

> US National Institutes of Health, RePORTER application 9953950, Engineering biomimetic knee menisci with zonal and anisotropic variations (5R01AR071457-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9953950. Licensed CC0.

---

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