Tissue Engineering Resource Center: TR&D1

SUMMARY Stimulus responsive materials with dynamic mechanical properties and reporter functions hold great promise in biomimicry, tissue engineering, disease models and delivery vehicles. On-demand stiffening hydrogel matrices, for instance, allow for control over the lineage commitment of stem and progenitor cells as well as fabrication of in vitro fibrosis models of heart, lung and liver. Similarly, gradual softening of the matrices enables the investigation of anti-fibrotic cell responses, matrix remodeling and resolution of the disease states. Responsive matrices also find use as cell nanocoating to bring mammalian cells to a bionic state and provide cytoprotection under harsh conditions during 3D bioprinting and injection-based cell transplantation. Yet, the challenge of combining tunable stimulus responsiveness, mechanics, bioactivity, and degradation for optimal cell-matrix interactions and host responses remain a challenge. In the current TRD1, we studied composites of silk protein with other biopolymers such as gelatin, alginate and hyaluronic acid involving their chemical modification for responsiveness, tunable mechanics and degradation rates. These materials were utilized as cytoprotective capsules for mammalian cells against hydrodynamic forces during capillary flow as well as for gel systems with reporter functions for oxygen levels. The renewal of TRD1 will focus on translation of these material formats into in vitro and in vivo practices. These directions will include: (a) scaffold materials for engineering specific tissues and disease states such as fibrosis, (b) preservation of cell viability and function during 3D printing and injection- based cell delivery, and (c) reporter matrices in the form of subcutaneous tattoos or microneedles for real time monitoring of physiological conditions. The overall goal is to adjust the reversible chemistry and dynamic mechanics of the matrices developed in current TRD1 for specific applications in TRD2 and TRD3. We plan to use a range of human cell lineages to test cell-material interactions and fabricate tissue models for in vitro assessment of material function and properties. The outcomes from the renewal will be new approaches to medical intervention for future clinical tests.