The Role of Percolation in the Hydrogel-to-Tissue Transition for Cartilage Growth

The encapsulation of living cells in a three-dimensional hydrogel offers tremendous potential for tissue engineering by providing instructive cues to cells and a structural support for new tissue formation. A critical barrier to success is the need to couple the degrading/breaking down of the hydrogel to the synthesis of new tissue in order to maintain mechanical integrity during the transition from hydrogel to tissue.

This project combines computational modeling and experimental studies to identify the underlying fundamental principles that govern tissue growth in a hydrogel. The outcomes from the project will enable hydrogel designs for a wide range of cell populations including those that have poor tissue synthesis capabilities (e.g., older adults), thus enabling a more personalized approach to tissue engineering.

Planned activities include active learning modules for K-12 and undergraduate students, the involvement of these students in research, and unique training opportunities to graduate students at the interface of materials, tissue engineering, and mathematical modeling.

The research goal of this project is to gain fundamental insight into the mechanisms that govern tissue growth in hydrogels. A functional requirement in the process of tissue growth is a seamless transition from hydrogel to tissue that retains mechanical integrity of the three-dimensional (3D) construct. One way to maintain connectivity during the transition is through the co-existence of an interpenetrating network made of hydrogel and tissue, a concept described by the theory of mechanical percolation.

To this end, this project introduces mechanical percolation into a physically-driven multiscale mathematical model to capture the mechanisms responsible for hydrogel degradation and neotissue growth. Applying an integrated experimental and computational approach, the overall research objectives for this project are to (a) demonstrate rational control over the gel-to-tissue transition at the cellular level, (b) build mesoscale heterogeneities to control the mechanical transition from gel-to-tissue, and (c) apply a model-assisted approach to designing hydrogels that achieve a seamless gel-to-tissue transition across different types of donors whose tissue synthesis capabilities vary.

The knowledge gained from this research will fill a critical gap in our current understanding of tissue growth in hydrogels and will aid in the successful translation of hydrogels for use in tissue engineering.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.