3D bioprinting of collagen to rebuild components of the human heart.

Collagen is the primary component of the extracellular matrix in the human body. It has proved challenging to fabricate collagen scaffolds capable of replicating the structure and function of tissues and organs. We present a method to 3D-bioprint collagen using freeform reversible embedding of suspended hydrogels (FRESH) to engineer components of the human heart at various scales, from capillaries to the full organ. Control of pH-driven gelation provides 20-micrometer filament resolution, a porous microstructure that enables rapid cellular infiltration and microvascularization, and mechanical strength for fabrication and perfusion of multiscale vasculature and tri-leaflet valves. We found that FRESH 3D-bioprinted hearts accurately reproduce patient-specific anatomical structure as determined by micro-computed tomography. Cardiac ventricles printed with human cardiomyocytes showed synchronized contractions, directional action potential propagation, and wall thickening up to 14% during peak systole.

Ethylene Oxide Sterilization Preserves Bioactivity and Attenuates Burst Release of Encapsulated Glial Cell Line Derived Neurotrophic Factor from Tissue Engineered Nerve Guides For Long Gap Peripheral Nerve Repair.

Synthetic nerve guides are widely utilized to reconstruct peripheral nerve defects that are less than three centimeters. However, there are no clinically available nerve guides that are approved to promote repair over long gaps (>3 cm). Many currently available guides are unable to sustain large defect regeneration either because of limitations in fabrication or short degradation times in vivo. Furthermore, current clinically available nerve guides do not contain neurotrophic factor delivery systems to promote nerve tissue regeneration over long gaps. The purpose of this paper is to describe the manufacturing parameters and sterilization procedures of a 5.2 cm poly(caprolactone) nerve conduit with embedded polymeric microspheres that encapsulate glial cell line-derived neurotrophic factor (GDNF) for implantation into a preclinical rhesus macaque 5 cm median nerve defect model. Nerve conduits were sterilized with room temperature ethylene oxide (RT EtO) and assessed for morphology as well as maintenance of porosity. Release kinetics and bioactivity of GDNF were also assessed in RT EtO sterilized guides. Scanning electron microscopy indicated that RT EtO treatment did not affect morphology and porosity percentage of nerve guides. Furthermore, RT EtO had no effect on GDNF bioactivity based on Schwannoma cell migration studies. RT EtO guides exhibited significantly slowed GDNF release compared to GDNF release from nonsterile guides indicating that EtO treatment may enhance the long-term delivery kinetics of GDNF from polymeric microspheres within the nerve guide.