Whereas current meniscal tissue-engineering approaches largely model the tissue using small strain approximations, this supplement aims to design tissue-engineered neomenisci based on optimization of hyperelastic parameters. Hyperelasticity accounts for the mechanical behavior of elastic materials at large or finite deformations, hereby defined as greater than 10% strain. This degree of deformation is commonly observed in physiological environments. For example, the medial posterior horn has been reported to undergo 40% strain under normal loading conditions, well beyond the threshold for small strain approximations. In this proposal, we will use computational and experimental methods to investigate tissue-engineered meniscus performance under large deformations, a key metric to assess translatability. We will examine several mechanical models to develop a quantitative and physiologically relevant characterization profile for native meniscus fibrocartilage (Aim 1). We will then optimize a regimen of exogenous stimuli and evaluate their effect on hyperelastic parameters, with particular interest in anisotropic changes (Aim 2). These parameters are central to establishing our design criteria for engineered neomenisci. Together, these aims represent an exceedingly novel approach to tissue-engineering and will drive the development of a mechanically robust meniscus regenerative treatment option.

Public Health Relevance

This supplement complements the parent grant and is an original proposal not previously reviewed by the Study Section. It has been prepared by the candidate, Dr. Gabriela Espinosa, in consultation with the parent grant?s PI, Dr. Kyriacos Athanasiou. The proposed work utilizes hyperelastic theory to develop physiologically relevant design criteria for engineered knee meniscus tissue, which will improve the outcomes of the parent grant, while also fulfilling Dr. Espinosa?s Individual Development Plan (IDP). Specifically, the proposed project offers opportunities to apply her strong foundation and extensive training in biomechanics while delving into new areas such as orthopaedics, tissue-engineering, and translational medicine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
3R01AR071457-04S1
Application #
9940622
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wang, Fei
Project Start
2019-09-30
Project End
2022-06-30
Budget Start
2019-09-30
Budget End
2020-06-30
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92617