(80e) Controlling Spatiotemporal Properties of Hydrogels to Improve Tissue Engineering

Photopolymerizable hydrogels are promising scaffolds for cell encapsulation and tissue engineering owing to their ease of formation, ability to incorporate numerous chemistries including degradable sequences, tunable mechanical properties, and ability to print three-dimensional structures. A functional requirement for degradable hydrogels used in tissue engineering is a seamless transition from hydrogel to tissue that retains mechanical integrity of the three-dimensional construct. We recently discovered heterogeneities across multiple length-scales that can explain how tissue grows when cells are encapsulated in a hydrogel. Due to cell-inhibition of radical-mediated polymerization, microscale heterogeneities emerge in the form of reduced hydrogel cross-linking surrounding cells. This means that hydrogel near cells degrades more quickly than the bulk hydrogel and creates a scenario where voids provide space for neotissue to form and connect. Mesoscale heterogeneities emerge in the form of cell clusters. Microtissue forms in the clusters due to the microscale heterogeneities and depending on their spatial distribution can form a percolated neotissue network. These heterogeneities offer a novel mechanism to achieve a successful gel-to-tissue mechanical transition first at the microscale and then at the mesoscale. For load-bearing tissues such as cartilage and bone, an additional challenge is that the scaffold must also support the mechanical forces that are prevalent in vivo. However, soft hydrogels are necessary to support cells and tissue growth. To overcome these disparate requirements, we have combined 3D printing using digital projection lithography to create 3D stiff scaffolds that are then infilled with a cell-laden soft hydrogel. This talk will highlight some of our efforts in developing these hybrid scaffolds for tissue engineering of cartilage, the osteochondral (i.e., bone-cartilage) interface, and the physis (i.e., growth plate).