3D Bioprinting for Organ Regeneration
TL;DR: An overview of recent advances in 3D biop printing technology, as well as design concepts of bioinks suitable for the bioprinting process, focusing more specifically on vasculature, neural networks, the heart and liver are provided.
Abstract: Regenerative medicine holds the promise of engineering functional tissues or organs to heal or replace abnormal and necrotic tissues/organs, offering hope for filling the gap between organ shortage and transplantation needs. Three-dimensional (3D) bioprinting is evolving into an unparalleled biomanufacturing technology due to its high-integration potential for patient-specific designs, precise and rapid manufacturing capabilities with high resolution, and unprecedented versatility. It enables precise control over multiple compositions, spatial distributions, and architectural accuracy/complexity, therefore achieving effective recapitulation of microstructure, architecture, mechanical properties, and biological functions of target tissues and organs. Here we provide an overview of recent advances in 3D bioprinting technology, as well as design concepts of bioinks suitable for the bioprinting process. We focus on the applications of this technology for engineering living organs, focusing more specifically on vasculature, neural networks, the heart and liver. We conclude with current challenges and the technical perspective for further development of 3D organ bioprinting.
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01 Jan 2009
TL;DR: Organ printing can be defined as layer-by-layer additive robotic biofabrication of three-dimensional functional living macrotissues and organ constructs using tissue spheroids as building blocks.
Abstract: Organ printing can be defined as layer-by-layer additive robotic biofabrication of three-dimensional functional living macrotissues and organ constructs using tissue spheroids as building blocks. The microtissues and tissue spheroids are living materials with certain measurable, evolving and potentially controllable composition, material and biological properties. Closely placed tissue spheroids undergo tissue fusion - a process that represents a fundamental biological and biophysical principle of developmental biology-inspired directed tissue self-assembly. It is possible to engineer small segments of an intraorgan branched vascular tree by using solid and lumenized vascular tissue spheroids. Organ printing could dramatically enhance and transform the field of tissue engineering by enabling large-scale industrial robotic biofabrication of living human organ constructs with "built-in" perfusable intraorgan branched vascular tree. Thus, organ printing is a new emerging enabling technology paradigm which represents a developmental biology-inspired alternative to classic biodegradable solid scaffold-based approaches in tissue engineering.
942 citations
TL;DR: Recent advances in the nanomaterial-enabled wearable sensors including temperature, electrophysiological, strain, tactile, electrochemical, and environmental sensors are presented in this review.
Abstract: Highly sensitive wearable sensors that can be conformably attached to human skin or integrated with textiles to monitor the physiological parameters of human body or the surrounding environment have garnered tremendous interest. Owing to the large surface area and outstanding material properties, nanomaterials are promising building blocks for wearable sensors. Recent advances in the nanomaterial-enabled wearable sensors including temperature, electrophysiological, strain, tactile, electrochemical, and environmental sensors are presented in this review. Integration of multiple sensors for multimodal sensing and integration with other components into wearable systems are summarized. Representative applications of nanomaterial-enabled wearable sensors for healthcare, including continuous health monitoring, daily and sports activity tracking, and multifunctional electronic skin are highlighted. Finally, challenges, opportunities, and future perspectives in the field of nanomaterial-enabled wearable sensors are discussed.
377 citations
TL;DR: The current status and contemporary issues of 3D bioprinting pertaining to the eleven organ systems of the human body including skeletal, muscular, nervous, lymphatic, endocrine, reproductive, integumentary, respiratory, digestive, urinary, and circulatory systems were critically reviewed.
370 citations
Cites background or methods from "3D Bioprinting for Organ Regenerati..."
...Automation, high precision, geometrical freedom and control (macro-morphology, pore size, porosity, interconnectivity), customizability, printability of wide range of materials, ability to incorporate and precise spatiotemporal placement of proteins, growth factors, drugs, DNA, and other biochemical cues along with the cells [5], wide range of cell density and possibility of cell density gradient, reproducibility, and repeatability are some of the many advantages of this technology....
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...Cell-laden bioinks were bioprinted using thermal DOD [96, 97], piezoelectric DOD [98, 99], and electrostatic DOD [100] inkjet bioprinting methods with a post-printing cell viability of N80% [5, 101]....
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...Microvalve bioprinting had been used to print several types of cells including HFF-1 fibroblasts and HaCaT keratinocytes [91], primary bladder smooth muscle cells (SMCs) [123, 124], and human alveolar epithelial type II cell line A54956 and the EA.hy926hybrid human cell line [125], with a post-printing cell viability of N80% [125]....
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TL;DR: This review summarizes the newest achievements and challenges of additive manufacturing in the field of pharmaceutical and biomedical research that have been published since 2015.
Abstract: Growing demand for customized pharmaceutics and medical devices makes the impact of additive manufacturing increased rapidly in recent years. The 3D printing has become one of the most revolutionary and powerful tool serving as a technology of precise manufacturing of individually developed dosage forms, tissue engineering and disease modeling. The current achievements include multifunctional drug delivery systems with accelerated release characteristic, adjustable and personalized dosage forms, implants and phantoms corresponding to specific patient anatomy as well as cell-based materials for regenerative medicine. This review summarizes the newest achievements and challenges of additive manufacturing in the field of pharmaceutical and biomedical research that have been published since 2015. Currently developed techniques of 3D printing are briefly described while comprehensive analysis of extrusion-based methods as the most intensively investigated is provided. The issue of printlets attributes, i.e. shape and size is described with regard to personalized dosage forms and medical devices manufacturing. The undeniable benefits of 3D printing are highlighted, however a critical view resulting from the limitations and challenges of the additive manufacturing is also included. The regulatory issue is pointed as well.
367 citations
TL;DR: Three-dimensional printing has significant potential as a fabrication method in creating scaffolds for tissue engineering, including the ability to create complex geometries, porosities, co-culture of multiple cells, and incorporate growth factors.
Abstract: Three-dimensional printing has significant potential as a fabrication method in creating scaffolds for tissue engineering. The applications of 3D printing in the field of regenerative medicine and tissue engineering are limited by the variety of biomaterials that can be used in this technology. Many researchers have developed novel biomaterials and compositions to enable their use in 3D printing methods. The advantages of fabricating scaffolds using 3D printing are numerous, including the ability to create complex geometries, porosities, co-culture of multiple cells, and incorporate growth factors. In this review, recently-developed biomaterials for different tissues are discussed. Biomaterials used in 3D printing are categorized into ceramics, polymers, and composites. Due to the nature of 3D printing methods, most of the ceramics are combined with polymers to enhance their printability. Polymer-based biomaterials are 3D printed mostly using extrusion-based printing and have a broader range of applications in regenerative medicine. The goal of tissue engineering is to fabricate functional and viable organs and, to achieve this, multiple biomaterials and fabrication methods need to be researched.
347 citations
Cites background or methods from "3D Bioprinting for Organ Regenerati..."
...Compared to inkjet 3D printing, extrusion-based 3D printing enables a continuous flow f the biomaterials resulting in an ease of operation and wider selection of biomaterials, including polymers, decellula z d matrices, cell-lad n hydrogels, spheroids, and aggregates [8]....
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...extrusion-based 3D printing enables a continuous flow of the biomaterials resulting in an ease of operation and wider selection of biomaterials, including polymers, decellularized matrices, cell-laden hydrogels, spheroids, and aggregates [8]....
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References
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TL;DR: This review will provide a comprehensive overview of general properties of alginate and its hydrogels, their biomedical applications, and suggest new perspectives for future studies with these polymers.
5,372 citations
TL;DR: 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation and developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.
Abstract: Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.
4,841 citations
TL;DR: The emerging principles of vascular growth provide exciting new perspectives, the translation of which might overcome the current limitations of pro- and antiangiogenic medicine.
2,278 citations
TL;DR: Some of the 'design principles' for recreating the interwoven set of biochemical and mechanical cues in the cellular microenvironment are discussed, and the methods for implementing them are discussed.
Abstract: The emergence of tissue engineering raises new possibilities for the study of complex physiological and pathophysiological processes in vitro. Many tools are now available to create 3D tissue models in vitro, but the blueprints for what to make have been slower to arrive. We discuss here some of the 'design principles' for recreating the interwoven set of biochemical and mechanical cues in the cellular microenvironment, and the methods for implementing them. We emphasize applications that involve epithelial tissues for which 3D models could explain mechanisms of disease or aid in drug development.
2,182 citations
TL;DR: The continuous generation of monolithic polymeric parts up to tens of centimeters in size with feature resolution below 100 micrometers is demonstrated and critical control parameters are delineated and shown that complex solid parts can be drawn out of the resin at rates of hundreds of millimeters per hour.
Abstract: Additive manufacturing processes such as 3D printing use time-consuming, stepwise layer-by-layer approaches to object fabrication. We demonstrate the continuous generation of monolithic polymeric parts up to tens of centimeters in size with feature resolution below 100 micrometers. Continuous liquid interface production is achieved with an oxygen-permeable window below the ultraviolet image projection plane, which creates a "dead zone" (persistent liquid interface) where photopolymerization is inhibited between the window and the polymerizing part. We delineate critical control parameters and show that complex solid parts can be drawn out of the resin at rates of hundreds of millimeters per hour. These print speeds allow parts to be produced in minutes instead of hours.
1,787 citations