Spatial Control of Cell Behavior via Interfacial Bioorthogonal Chemistry

University Of Delaware, Newark DE

Investigators

Abstract

Spatial Control of Stem Cell Behavior via Interfacial Bioorthogonal Chemistry (NSF DMR, Biomaterials Program # DMR-1506613) Non-technical: Tissue engineering holds promise for creating off-the-shelf, implantable tissues or organs for the betterment of human health. Successful engineering of functional tissues requires the environment in which the cells originally reside in vivo be recreated ex vivo. In this project, a biomimetic scaffold will be created by combining a gelatinous material exhibiting desired spatial gradients with synthetic fibers displaying biochemical signals in a repetitive fashion. The individual components and the integrated scaffold will be produced using a novel process that takes advantage of an ultrafast, highly efficient coupling reaction. Such a process permits the spatial control of scaffold properties without having to rely on external, potentially toxic triggers or templates, thereby enabling facile incorporation of the patient's cells in the scaffold in 3D. The cell-populated scaffold will be mechanically stimulated to enhance tissue growth. The ultimate goal is to create tissues with the correct organization and proper functions. This work will enable the production of sophisticated materials to improve the quality of life for patients suffering from various diseases, thus justifying the public support. The PIs outreach and education efforts will help maintain the United States' global competitiveness. In addition to course development, student training, effort will be dedicated to the engaging and empowering of pre-service, early childhood teachers who will inspire the next generation scientists. Technical: This award to the University of Delaware (UD) aims to develop synthetic matrices with anisotropic features and spatial gradients to control the behavior of 3D encapsulated mesenchymal stem cells (MSCs) for the engineering of mechanically active soft tissues. The PIs will accomplish this goal by integrating a hyaluronic acid (HA)-based hydrogel with synthetic fibers produced de novo using designed monomers. The HA hydrogel will exhibit spatial variations of matrix stiffness and ligand density while the synthetic fibers will mimic the structure and the function of fibrous proteins found in the native extracellular matrix. Both the gel and the fiber components will be produced via a novel interfacial polymerization process that takes advantage of the rapid, bioorthogonal and highly efficient cycloaddition reaction between s-tetrazine (Tz) and trans-cyclooctene (TCO). The PIs will evaluate the potential of the synthetic matrix, combined with a dynamic culture device, in guiding the spatial differentiation of MSCs. The ultimate goal is to produce a multilayered construct with anisotropic features that reflect the microstructure of the targeted tissue. The proposed research program will provide a fertile training ground for undergraduate and graduate students, thus contributing to the continued growth of the biomedical engineering program at UD. The research project will also provide a platform for engaging and empowering early childhood teachers.