PROJECT SUMMARY This Idaho INBRE team science administrative supplement titled, “Establishing a developmentally inspired biomaterial platform to direct stem cell tenogenesis” fits the Idaho INBRE-4 parent grant scientific theme of Cell Signaling. Tendons are strong, collagenous musculoskeletal tissues that transfer mechanical forces from muscle to bone. There is a clinical need for novel regenerative therapies to treat tendon injuries as healing is limited and injuries are associated with long-term loss of function. Three interdisciplinary investigators will work as a team to leverage their individual expertise to design a biomaterial polymer platform to control tenogenesis. Our team includes experts in the areas of tendon development and mesenchymal stem cell (MSC) differentiation (Dr. Schiele – Biomedical Engineering), polymeric hydrogels and biomaterials (Dr. Bernards – Chemical Engineering), and peptide synthesis and organic chemistry (Dr. Waynant – Chemistry). There is a limited understanding of the biochemical and mechanical factors that regulate tenogenesis. Normal embryonic and postnatal tendon development will inform our tenogenic strategy. By leveraging the strengths of the team, we will advance a novel hydrogel platform and knowledge of tenogenic regulators. We will determine the combination of developmentally identified biochemical and mechanical factors that regulate tenogenesis and deliver those factors with a novel biomaterial platform. We hypothesize that developmental factors can be rationally designed into a new class of zwitterionic cross-linked polyampholyte hydrogels to direct MSC into functional tendon cells. The project has two specific aims. Specific Aim 1 develops our team and defines the roles that peptides mimicking the developmentally identified cell-cell junction proteins (cadherin-11 and N- cadherin) and extracellular matrix proteins (fibronection and collagen) have on the induction of stem cell tenogenesis. These signals will be delivered from polyampholyte hydrogels synthesized with novel zwitterionic cross-linkers, which are designed to control the presentation of the desired cell signaling peptides. Specific Aim 2 expands this family of zwitterionic cross-linkers to finetune the mechanical properties of the polyampholyte hydrogels to match specific stages of tendon development. This will determine how the tissue elastic modulus and biochemical signaling together control tenogenesis. To meet Idaho INBRE goals, this team science project also provides opportunities for undergraduate and graduate students to design and test this biomaterial platform, which further enhances the pipeline of well-trained biomedical researchers. The combined results from this team effort will be a family of tunable zwitterionic cross-linker species that are incorporated into polyampholyte hydrogels designed to deliver biochemical and mechanical developmental factors that regulate tenogenesis. We anticipate this will represent a significa...