# Ice-free Cryopreservation with Nanowarming for Banking of Viable Meniscal Transplants

> **NIH NIH P20** · CLEMSON UNIVERSITY · 2024 · $220,769

## Abstract

SUMMARY
Nearly a million Americans suffer from meniscus tears every year, and 80% of patients who undergo partial or
total meniscus removal subsequently develop pain, transient effusion, and knee osteoarthritis. Currently,
meniscal allograft transplantation (MAT) with human cadaver tissues is considered medically necessary for
treatments with symptomatic post meniscectomy knees with major meniscus loss. Although MAT enables
favorable outcomes in the long term, the challenge of donor-recipient size-matching strongly limits broad
implementation of MAT since ineffective preservation techniques restrict the number of available fresh grafts.
Our ultimate, long-term objective is to maintain cell viability, tissue structure and biomechanical integrity of
meniscal allografts for the purpose of long-term storage, thereby overcoming the size-matching challenge. Our
previous studies have demonstrated that ice-free cryopreservation by vitrification combined with nanowarming
is a promising preservation method for preserving living cells and matrix structure in large avascular tissues.
However, this method has encountered critical challenges when applied to meniscal tissues, the major hurdle
being the transport limitation of cryoprotectant (CPA) molecules in the meniscus. The large and complex
meniscal structure and ECM composition prevents uniform distribution of CPA throughout the tissue, thereby
causing ice crystal formation during cooling, which damages living cells and tissue structure. To overcome the
CPA transport limitation, two critical knowledge gaps need to be filled: 1) location-specific mass transport
mechanism of CPA molecules in the whole meniscus, 2) location-specific effects of CPA concentration and
exposure time (CPA toxicity) on meniscal viability. Herein, we hypothesize that meniscal allografts loaded with
adequate and toxically tolerable CPAs can be preserved without the loss of viability and functionality by
vitrification integrated with nanowarming compared to conventionally cryopreserved allografts. Specifically, we
aim to 1) determine location-specific porcine meniscal structure- and composition-dependent CPA transport
properties in the whole porcine meniscus, 2) investigate location-specific effects of CPA concentration and
exposure time on meniscal viability and optimize both parameters to achieve optimal viability after vitrification,
and 3) evaluate in vivo functionality of vitrified meniscal allografts in a 4-month preclinical transplant study using
a porcine model. Collectively, these aims will demonstrate our concept that the vitrification method can be used
to preserve living cells and tissue structures in meniscal allografts in a pig model. Future work will combine the
developed methodologies and our computational model to optimize viability of human meniscal allografts after
CPA addition and vitrification to identify the optimal CPA loading and vitrification protocol for each donor graft.
Further, by incorporating patient-spe...

## Key facts

- **NIH application ID:** 10912648
- **Project number:** 5P20GM121342-07
- **Recipient organization:** CLEMSON UNIVERSITY
- **Principal Investigator:** Shangping Wang
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $220,769
- **Award type:** 5
- **Project period:** 2018-09-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912648

## Citation

> US National Institutes of Health, RePORTER application 10912648, Ice-free Cryopreservation with Nanowarming for Banking of Viable Meniscal Transplants (5P20GM121342-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10912648. Licensed CC0.

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