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

将活细胞封装在三维水凝胶中，通过为细胞提供指导性线索和新组织形成的结构支持，为组织工程提供了巨大的潜力。成功的关键障碍是需要将水凝胶的降解/分解与新组织的合成相结合，以便在从水凝胶到组织的转变期间保持机械完整性。该项目结合了计算建模和实验研究，以确定管理水凝胶中组织生长的基本原则。该项目的成果将使水凝胶设计能够用于广泛的细胞群，包括那些组织合成能力差的细胞群（例如，老年人），从而实现更个性化的组织工程方法。计划中的活动包括K-12和本科生的主动学习模块，这些学生参与研究，以及在材料，组织工程和数学建模界面上为研究生提供独特的培训机会。 该项目的研究目标是获得对水凝胶中组织生长机制的基本见解。组织生长过程中的功能要求是从水凝胶到组织的无缝过渡，其保持三维（3D）构造的机械完整性。在过渡期间保持连通性的一种方法是通过由水凝胶和组织制成的互穿网络的共存，这是机械渗透理论描述的概念。为此，该项目将机械渗滤引入物理驱动的多尺度数学模型，以捕获负责水凝胶降解和新组织生长的机制。应用综合的实验和计算方法，该项目的总体研究目标是（a）在细胞水平上证明对凝胶到组织转变的合理控制，（B）建立介观尺度的非均匀性以控制从凝胶到组织的机械转变，和（c）应用模型辅助方法来设计水凝胶，其实现无缝的凝胶-不同类型供体之间的组织过渡，其组织合成能力不同。从这项研究中获得的知识将填补我们目前对水凝胶中组织生长的理解的关键空白，并将有助于成功地将水凝胶转化为用于组织工程的水凝胶。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

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.