Bioprinting is a rapidly developing technology for the precise design and manufacture of tissues in various biological systems or organs.Coaxial extrusion bioprinting,an emergent branch,has demonstrated a strong poten...Bioprinting is a rapidly developing technology for the precise design and manufacture of tissues in various biological systems or organs.Coaxial extrusion bioprinting,an emergent branch,has demonstrated a strong potential to enhance bioprinting's engineering versatility.Coaxial bioprinting assists in the fabrication of complex tissue constructs,by enabling concentric deposition of biomaterials.The fabricated tissue constructs started with simple,tubular vasculature but have been substantially developed to integrate complex cell composition and self-assembly,ECM patterning,controlled release,and multi-material gradient profiles.This review article begins with a brief overview of coaxial printing history,followed by an introduction of crucial engineering components.Afterward,we review the recent progress and untapped potential in each specific organ or biological system,and demonstrate how coaxial bioprinting facilitates the creation of tissue constructs.Ultimately,we conclude that this growing technology will contribute significantly to capabilities in the fields of in vitro modeling,pharmaceutical development,and clinical regenerative medicine.展开更多
The current methods of generating human cerebral organoids rely excessively on the use of Matrigel or other external extracellular matrices(ECM)for cell micro-environmental modulation.Matrigel embedding is problematic...The current methods of generating human cerebral organoids rely excessively on the use of Matrigel or other external extracellular matrices(ECM)for cell micro-environmental modulation.Matrigel embedding is problematic for long-term culture and clinical applications due to high inconsistency and other limitations.In this study,we developed a novel microwell culture platform based on 3D printing.This platform,without using Matrigel or external signaling molecules(i.e.,SMAD and Wnt inhibitors),successfully generated matured human cerebral organoids with robust formation of high-level features(i.e.,wrinkling/folding,lumens,neuronal layers).The formation and timing were comparable or superior to the current Matrigel methods,yet with improved consistency.The effect of microwell geometries(curvature and resolution)and coating materials(i.e.,mPEG,Lipidure,BSA)was studied,showing that mPEG outperformed all other coating materials,while curved-bottom microwells outperformed flat-bottom ones.In addition,high-resolution printing outperformed low-resolution printing by creating faithful,isotropically-shaped microwells.The trend of these effects was consistent across all developmental characteristics,including EB formation efficiency and sphericity,organoid size,wrinkling index,lumen size and thickness,and neuronal layer thickness.Overall,the microwell device that was mPEG-coated,high-resolution printed,and bottom curved demonstrated the highest efficacy in promoting organoid development.This platform provided a promising strategy for generating uniform and mature human cerebral organoids as an alternative to Matrigel/ECM-embedding methods.展开更多
基金We thank Utah State University's College of Engineering Undergraduate Research Program(EURP)for supporting Andrew Kjar and Bailey McFarland.
文摘Bioprinting is a rapidly developing technology for the precise design and manufacture of tissues in various biological systems or organs.Coaxial extrusion bioprinting,an emergent branch,has demonstrated a strong potential to enhance bioprinting's engineering versatility.Coaxial bioprinting assists in the fabrication of complex tissue constructs,by enabling concentric deposition of biomaterials.The fabricated tissue constructs started with simple,tubular vasculature but have been substantially developed to integrate complex cell composition and self-assembly,ECM patterning,controlled release,and multi-material gradient profiles.This review article begins with a brief overview of coaxial printing history,followed by an introduction of crucial engineering components.Afterward,we review the recent progress and untapped potential in each specific organ or biological system,and demonstrate how coaxial bioprinting facilitates the creation of tissue constructs.Ultimately,we conclude that this growing technology will contribute significantly to capabilities in the fields of in vitro modeling,pharmaceutical development,and clinical regenerative medicine.
基金We thank Hemdeep Patel from the ResinWorks3D company for providing us the high-resolution 3D printed mold devices as a gift.We also thank Angela Clyde for the initial discussion on device design.We thank Utah State University’s College of Engineering Undergraduate Research Program(EURP)for supporting Andrew Kjar.We also thank Utah State University Research Catalyst(RC)program for supporting Cheng Chen.
文摘The current methods of generating human cerebral organoids rely excessively on the use of Matrigel or other external extracellular matrices(ECM)for cell micro-environmental modulation.Matrigel embedding is problematic for long-term culture and clinical applications due to high inconsistency and other limitations.In this study,we developed a novel microwell culture platform based on 3D printing.This platform,without using Matrigel or external signaling molecules(i.e.,SMAD and Wnt inhibitors),successfully generated matured human cerebral organoids with robust formation of high-level features(i.e.,wrinkling/folding,lumens,neuronal layers).The formation and timing were comparable or superior to the current Matrigel methods,yet with improved consistency.The effect of microwell geometries(curvature and resolution)and coating materials(i.e.,mPEG,Lipidure,BSA)was studied,showing that mPEG outperformed all other coating materials,while curved-bottom microwells outperformed flat-bottom ones.In addition,high-resolution printing outperformed low-resolution printing by creating faithful,isotropically-shaped microwells.The trend of these effects was consistent across all developmental characteristics,including EB formation efficiency and sphericity,organoid size,wrinkling index,lumen size and thickness,and neuronal layer thickness.Overall,the microwell device that was mPEG-coated,high-resolution printed,and bottom curved demonstrated the highest efficacy in promoting organoid development.This platform provided a promising strategy for generating uniform and mature human cerebral organoids as an alternative to Matrigel/ECM-embedding methods.