Extracellular Matrix-Based Microfabrication to Generate Advanced Models of Human Tissue Function

Abstract

Additive manufacturing has been adopted in tissue engineering for generating biological scaffolds with complex geometry. However, there are still critical gaps to be filled in the field. For example, currently available skin models are incapable of conferring adhesive strength between dermis and epidermis. Meanwhile, inclusion of contiguous muscle in complex cardiac tissues recapitulating chambered structure of the heart has not yet been achieved, and most engineered cardiac tissues are too small to accommodate the sizes of medical devices to serve as a testbed. Here we take advantage of current understanding of extracellular matrix (ECM)-cell interactions in combination with engineering strategies to address these issues. In the first study, a 3D model of the dermoepidermal junction (DEJ) was created using a layer-by-layer approach with physiologically-relevant ECM components. The model is amenable to lap shear testing and capable of discerning the difference between wild-type and patient-derived keratinocytes, making it applicable for associated therapeutics. The other two studies in this work capitalize on the ability of 3D bioprinting to produce complex structures with soft biomaterials as well as in situ differentiation of stem cells to advance the functionality of macroscale cardiac tissues. An optimized bioink was developed to support stem cell proliferation and cardiac differentiation. The resultant human chambered muscle pumps (hChaMPs) exhibit contiguous muscle layers with electromechanical coupling and measurable pressure-volume dynamics. A similar approach was used to generate centimeter-scale cardiac disks with soft sensors to map device intervention. In the future, these models will be valuable for disease modeling and device testing while propelling the possibility of regenerative medicine.