In Situ Bioprinting of Planar Biomaterials and Tissues

The goal of regenerative medicine is the synthesis of replacement tissue by positioning vital cells in three-dimensional (3D) patterns representing the arrangement, characteristics and functionality of natural tissue. The largest organ in humans - skin - possesses a unique hierarchical structure, comprised of cell populations whose fate and functionality is governed by their position. In severe burn injuries, effective strategies that ensure prompt and effective wound closure are essential for survival. Acellular substitutes require grafting and thus cause additional wounds, while cellular substitutes need long culture times, typically 3 - 4 weeks. In this thesis, a handheld instrument is presented that enables bioprinting of architected planar biomaterials and tissues in an approach that is compatible with in vitro and in vivo applications. Enzymatically, ionically, or light polymerizable biopolymer solutions that may contain skin cells are spatially organized to geometries resembling the skin using a microfabricated printhead and deposited onto a target surface. Homogeneous and architected (i.e., bi-layered and stripe-patterned) sheets are consistently formed and characterized. Cell-laden tissues were studied in vitro. Proof-of-concept experiments in small (murine) and big animal (porcine) wound models demonstrate the compatibility of the approach with in vivo requirements. The presented strategy enables the formation of organized soft tissues in a one-step manner that does not require multi-axis printhead translation or manipulation of printed constructs. With macroscopic and microscopic target surface specificity, in situ bioprinting shows great promises as an alternative bio-fabrication method for making tissue substitutes on arbitrary surfaces.Ph.D.2020-10-30 00:00:0