Towards 4D Bioprinting

Towards 4D Printing presents the current state of three-dimensional (3D) bioprinting and its recent offspring, 4D bioprinting. These are attractive approaches to tissue engineering because they hold the promise of building bulky tissue constructs with incorporated vasculature. Starting with the discussion of 3D and 4D printing of inanimate objects, the book presents several 3D bioprinting techniques and points out the challenges imposed by living cells on the bioprinting process. It argues that, in order to fine-tune the bioprinter, one needs a quantitative analysis of the conditions experienced by cells during printing. Once the printing is over, the construct evolves according to mechanisms known from developmental biology. These are described in the book along with computer simulations that aim to predict the outcome of 3D bioprinting. In addition, the book provides the latest information on the principles and applications of 4D bioprinting, such as for medical devices and assistive technology. The last chapter discusses the perspectives of the field. This book provides an up-to date description of the theoretical tools developed for the optimization of 3D bioprinting, presents the morphogenetic mechanisms responsible for the post-printing evolution of the bioprinted construct and describing computational methods for simulating this evolution, and discusses the leap from 3D to 4D bioprinting in the light of the latest developments in the field. Most importantly, Towards 4D Printing explains the importance of theoretical modeling for the progress of 3D and 4D bioprinting. Presents theoretical tools needed for the optimization of the bioprinting process Describes the principles and implementation of computer simulations needed to predict the outcome of 3D bioprinting Analyzes the distinctive features of 4D bioprinting along with its applications and perspectives

Abstract : Tissue engineering and regenerative medicine (TE&RM) has made continuous advancements by extending three-dimensional (3D) printing towards the development and fabrication of biomimetic scaffolds composed of biomimetic natural and synthetic materials. Although several clinical applications of 3D-printed scaffolds made of classical biomaterials have yielded promising results, current basic research trends have shifted towards rendering scaffolds "smart" or dynamically responsive where shape changes are induced by external stimulation (ie. electromagnetic radiation, mechanical stress, heat) or physiological changes in the local microenvironment through pre-designed mechanisms of action. Although a bulk of the research efforts have led to high-impact publications demonstrating the capabilities of these technologies, hardly any studies have been published illustrating the application of these research efforts in a clinical context. Herein, we will discuss current trends and advancements of 3D printable bioinks and highlight the most recent developments (2015-present) of 3D-printed smart materials also commonly referred to as 4D printing/programmable matter. We will conclude with a prospective opinion of this research field where innovation is synonymous with risk-taking. High-risk, high-reward research founded on revolutionary innovations are often disruptive and lead to new paradigms; conclusively the 4D printing can be disruptive, because it has the potential to change the current paradigm by changing the question from "what can we do with these materials/technologies?" to "how can we move the concept/technology forward to achieve what we need". Highlights: Programmable matter needs to translate its potential to be a disruptive technology via high quality applied research. A paradigm shift from "what can we do with these materials?" to "how can we move the concept/technology forward?" is needed. Physiological and biomechanical constraints based on tissue microenvironment are not considered in smart material design. The lack of in-depth follow-up studies have resulted in poor clinical translation of smart material concepts. Global collaborative efforts spur and facilitate development, characterisation and validation of new bioinks.

With a turnover of some 5-15 billion € / year, the additive manufacturing has industrial niches bearers thanks to processes and materials more and more optimized. While some niches still exist on the application of additive techniques in traditional fields (from jewelery to food for example), several trends emerge, using new concepts: collective production, realization of objects at once (without addition Of material), micro-fluidic, 4D printing exploiting programmable materials and materials, bio-printing, etc. There are both opportunities for new markets, promises not envisaged less than 10 years ago, but difficulties in reaching them.

Despite great scientific and clinical successes, few tissue engineering products have so far made their way to the industrial and commercial phase, depriving patients to benefit from innovative treatments. Producing advanced therapy medicinal products remains a cumbersome process with costs, reproducibility and scalability issues. Automation of production processes should be key to achieve quality controlled and repeatable biomanufacturing. Poietis develops biomanufacturing solutions based on bioprinting technologies for the design and the production of tissues, like the full thickness skin model Poieskinu00ae.The fabrication process follows three main steps: (1) tissue design where the 3D patterns of cells and materials are defined through a proprietary tissue CAD software; (2) tissue biofabrication consisting in the layer-by-layer deposition of collagen, fibroblasts and keratinocytes; (3) tissue maturation during which cell patterns evolve towards the final functional tissue architecture. Biofabrication is performed using the proprietary Next-Generation Bioprinting platform combining microvalve and laser assisted bioprinting. Unit controls is performed using embedded image analysis tools to assess production quality. The Quality-by-Design methology is used to determine CMA (critical material attributes) and CPP (critical process parameters).We demonstrate a control over the 3D cell organization and a relation between the initial 3D cell pattern and the cell reorganization dynamics. The use of the Quality-By-Design methodology enabled to hierarchize the CMA and CPP and consequently incrementaly improve the reproducibility and quality of the produced tissues. The biofabrication strategy described here is generic and can be applied to the design and production of any tissue. The routine production of Poieskinu00ae for in vitro research applications demonstrates the industrial maturity of bioprinting and is a key milestone towards the development of clinical bioprinters for the production of tissue grafts.

With a turnover of some 5-15 billion € / year, the additive manufacturing has industrial niches bearers thanks to processes and materials more and more optimized. While some niches still exist on the application of additive techniques in traditional fields (from jewelery to food for example), several trends emerge, using new concepts: collective production, realization of objects at once (without addition Of material), micro-fluidic, 4D printing exploiting programmable materials and materials, bio-printing, etc. There are both opportunities for new markets, promises not envisaged less than 10 years ago, but difficulties in reaching them.

This book is comprehensive in nature with contributions by leading world experts in 3D bioprinting related to regenerative engineering. It includes history, incorporating the process and methods used in bioprinting. Significant sections will be reserved for the applications of the types of tissues generated by using bioprinting, along with an overview of different technologies used in bioprinting. In addition to equipment, the book also describes the different biomaterials and cells used in these approaches. Overall this is a book that includes both entry-level knowledge and advanced methods and techniques. Applications will emphasize engineering and clinical principles.

This book is comprehensive in nature with contributions by leading world experts in 3D bioprinting related to regenerative engineering. It includes history, incorporating the process and methods used in bioprinting. Significant sections will be reserved for the applications of the types of tissues generated by using bioprinting, along with an overview of different technologies used in bioprinting. In addition to equipment, the book also describes the different biomaterials and cells used in these approaches. Overall this is a book that includes both entry-level knowledge and advanced methods and techniques. Applications will emphasize engineering and clinical principles.

What if structures could build themselves or adapt to fluctuating environments? Skylar Tibbits, Director of the Self-Assembly Lab in the Department of Architecture at MIT, Cambridge, MA, crosses the boundaries between architecture, biology, materials science and the arts, to envision a world where material components can self-assemble to provide adapting structures and optimized fabrication solutions. The book examines the three main ingredients for self-assembly, includes interviews with practitioners involved in the work and presents research projects related to these topics to provide a complete first look at exciting future technologies in construction and self-transforming material products.

3D Printing Technology in Nanomedicine provides an integrated and introductory look into the rapidly evolving field of nanobiotechnology. It demystifies the processes of commercialization and discusses legal and regulatory considerations. With a focus on nanoscale processes and biomedical applications, users will find this to be a comprehensive resource on how 3D printing can be utilized in a range of areas, including the diagnosis and treatment of a variety of human diseases. Examines the emerging market of 3D-printed biomaterials and their clinical applications, with a particular focus on both commercial and premarket tools Examines the promising market of 3D-printed nanoparticles, nanomaterial, biomaterials, composite nanomaterial and their clinical applications in the cardiovascular and chemotherapy realms Develops the concept of integrating different technologies along the hierarchical structure of biological systems

3D and 4D Printing of Polymer Nanocomposite Materials: Processing, Applications, and Challenges covers advanced 3D and 4D printing processes and the latest developments in novel polymer-based printing materials, thus enabling the reader to understand and benefit from the advantages of this groundbreaking technology. The book presents processes, materials selection, and printability issues, along with sections on the preparation of polymer composite materials for 3D and 4D printing. Across the book, advanced printing techniques are covered and discussed thoroughly, including fused deposition modeling (FDM), selective laser sintering (SLS), selective laser melting (SLM), electron beam melting (EBM), inkjet 3D printing (3DP), stereolithography (SLA), and 3D plotting. Finally, major applications areas are discussed, including electronic, aerospace, construction and biomedical applications, with detailed information on the design, fabrication and processing methods required in each case. Provides a thorough, clear understanding of polymer preparation techniques and 3D and 4D printing processes, with a view to specific applications Examines synthesis, formation methodology, the dispersion of fillers, characterization, properties, and performance of polymer nanocomposites Explores the possibilities of 4D printing, covering the usage of stimuli responsive hydrogels and shape memory polymers

This book offers readers a comprehensive introduction to the techniques and application of 3D printing in cardiovascular medicine. To do so, it addresses the history, concepts, and methods of 3D printing, choice of printing materials for clinical purposes, personalized planning of cardiac surgery and transcatheter interventions with patient-specific models, enhancement of patient-physician communication, simulation of endovascular procedures, and advances in 3D bio-printing. The book particularly focuses on the application of 3D printing to improve the efficacy and safety of cardiac interventions, and to promote the realization of precision medical care. The book gathers contributions by an international team of experts in the field of cardiovascular medicine, who combine the latest findings with their own practical experience in using 3D printing to support the diagnosis and treatment of a wide range of cardiovascular diseases. They present in-depth discussions in the fields of congenital heart disease, valvular disease, coronary artery disease, cardiomyopathy, left atrial appendage occlusion, cardiac tumors and vascular diseases.

3D and 4D Printing of Polymer Nanocomposite Materials: Processing, Applications, and Challenges covers advanced 3D and 4D printing processes and the latest developments in novel polymer-based printing materials, thus enabling the reader to understand and benefit from the advantages of this groundbreaking technology. The book presents processes, materials selection, and printability issues, along with sections on the preparation of polymer composite materials for 3D and 4D printing. Across the book, advanced printing techniques are covered and discussed thoroughly, including fused deposition modeling (FDM), selective laser sintering (SLS), selective laser melting (SLM), electron beam melting (EBM), inkjet 3D printing (3DP), stereolithography (SLA), and 3D plotting. Finally, major applications areas are discussed, including electronic, aerospace, construction and biomedical applications, with detailed information on the design, fabrication and processing methods required in each case. Provides a thorough, clear understanding of polymer preparation techniques and 3D and 4D printing processes, with a view to specific applications Examines synthesis, formation methodology, the dispersion of fillers, characterization, properties, and performance of polymer nanocomposites Explores the possibilities of 4D printing, covering the usage of stimuli responsive hydrogels and shape memory polymers

In 1984, additive manufacturing represented a new methodology for manipulating matter, consisting of harnessing materials and/or energy to create three-dimensional physical objects. Today, additive manufacturing technologies represent a market of around 5 billion euros per year, with an annual growth between 20 and 30%. Different processes, materials and dimensions (from nanometer to decameter) within additive manufacturing techniques have led to 70,000 publications on this topic and to several thousand patents with applications as wide-ranging as domestic uses. Volume 1 of this series of books presents these different technologies with illustrative industrial examples. In addition to the strengths of 3D methods, this book also covers their weaknesses and the developments envisaged in terms of incremental innovations to overcome them.

3D printing is forecast to revolutionise the pharmaceutical sector, changing the face of medicine development, manufacture and use. Potential applications range from pre-clinical drug development and dosage form design through to the fabrication of functionalised implants and regenerative medicine. Within clinical pharmacy practice, printing technologies may finally lead to the concept of personalised medicines becoming a reality. This volume aims to be the definitive resource for anyone thinking of developing or using 3D printing technologies in the pharmaceutical sector, with a strong focus on the translation of printing technologies to a clinical setting. This text brings together leading experts to provide extensive information on an array of 3D printing techniques, reviewing the current printing technologies in the pharmaceutical manufacturing supply chain, in particular, highlighting the state-of-the-art applications in medicine and discussing modern drug product manufacture from a regulatory perspective. This book is a highly valuable resource for a range of demographics, including academic researchers and the pharmaceutical industry, providing a comprehensive inventory detailing the current and future applications of 3D printing in pharmaceuticals. Abdul W. Basit is Professor of Pharmaceutics at the UCL School of Pharmacy, University College London. Abdul’s research sits at the interface between pharmaceutical science and gastroenterology, forging links between basic science and clinical outcomes. He leads a large and multidisciplinary research group, and the goal of his work is to further the understanding of gastrointestinal physiology by fundamental research. So far, this knowledge has been translated into the design of new technologies and improved disease treatments, many of which are currently in late-stage clinical trials. He has published over 350 papers, book chapters and abstracts and delivered more than 250 invited research presentations. Abdul is also a serial entrepreneur and has filed 25 patents and founded 3 pharmaceutical companies (Kuecept, Intract Pharma, FabRx). Abdul is a frequent speaker at international conferences, serves as a consultant to many pharmaceutical companies and is on the advisory boards of scientific journals, healthcare organisations and charitable bodies. He is the European Editor of the International Journal of Pharmaceutics. Abdul was the recipient of the Young Investigator Award in Pharmaceutics and Pharmaceutical Technology from the American Association of Pharmaceutical Scientists (AAPS) and is the only non-North American scientist to receive this award. He was also the recipient of the Academy of Pharmaceutical Sciences (APS) award. Simon Gaisford holds a Chair in Pharmaceutics and is Head of the Department of Pharmaceutics at the UCL School of Pharmacy, University College London. He has published 110 papers, 8 book chapters and 4 authored books. His research is focused on novel technologies for manufacturing medicines, particularly using ink-jet printing and 3D printing, and he is an expert in the physico-chemical characterisation of compounds and formulations with thermal methods and calorimetry.

3D Printing in Medicine examines the emerging market of 3D-printed biomaterials and its clinical applications. With a particular focus on both commercial and premarket tools, the book looks at their applications within medicine and the future outlook for the field. The book begins with a discussion of the fundamentals of 3D printing, including topics such as materials, and hardware. Chapters go on to cover applications within medicine such as computational analysis of 3D printed constructs, personalized 3D printing and 3D cell and organ printing. The concluding chapters in the book review the applications of 3D printing in diagnostics, drug development, 3D-printed disease models and 3D printers for surgical practice. With a strong focus on the translation of 3D printing technology to a clinical setting, this book is a valuable resource for scientists and engineers working in biomaterial, biomedical, and nanotechnology based industries and academia. Provides a comprehensive and authoritative overview of all the medical applications of 3D printing biomaterials and technologies Focuses on the emerging market of 3D printed biomaterials in clinical applications Reviews both commercial and under development materials, tools, their applications, and future evolution

Essentials of 3D Biofabrication and Translation discusses the techniques that are making bioprinting a viable alternative in regenerative medicine. The book runs the gamut of topics related to the subject, including hydrogels and polymers, nanotechnology, toxicity testing, and drug screening platforms, also introducing current applications in the cardiac, skeletal, and nervous systems, and organ construction. Leaders in clinical medicine and translational science provide a global perspective of the transformative nature of this field, including the use of cells, biomaterials, and macromolecules to create basic building blocks of tissues and organs, all of which are driving the field of biofabrication to transform regenerative medicine. Provides a new and versatile method to fabricating living tissue Discusses future applications for 3D bioprinting technologies, including use in the cardiac, skeletal, and nervous systems, and organ construction Describes current approaches and future challenges for translational science Runs the gamut of topics related to the subject, from hydrogels and polymers to nanotechnology, toxicity testing, and drug screening platforms

Abstract: Despite the tremendous potential of bioprinting techniques toward the fabrication of highly complex biological structures and the flourishing progress in 3D bioprinting, the most critical challenge of the current approaches is the printing of hollow tubular structures. In this work, an advanced 4D biofabrication approach, based on printing of shape‐morphing biopolymer hydrogels, is developed for the fabrication of hollow self‐folding tubes with unprecedented control over their diameters and architectures at high resolution. The versatility of the approach is demonstrated by employing two different biopolymers (alginate and hyaluronic acid) and mouse bone marrow stromal cells. Harnessing the printing and postprinting parameters allows attaining average internal tube diameters as low as 20 μm, which is not yet achievable by other existing bioprinting/biofabrication approaches and is comparable to the diameters of the smallest blood vessels. The proposed 4D biofabrication process does not pose any negative effect on the viability of the printed cells, and the self‐folded hydrogel‐based tubes support cell survival for at least 7 d without any decrease in cell viability. Consequently, the presented 4D biofabrication strategy allows the production of dynamically reconfigurable architectures with tunable functionality and responsiveness, governed by the selection of suitable materials and cells. Abstract : An advanced 4D biofabrication approach, based on shape‐morphing biopolymer hydrogels, is presented for the fabrication of hollow self‐folding tubes with unprecedented control over their diameters and architectures at high resolution. The approach paves new avenues for the creation of tailored cell‐laden shape‐morphing architectures for tissue engineering and regenerative medicine applications.

Advanced 3D-Printed Systems and Nanosystems for Drug Delivery and Tissue Engineering explores the intricacies of nanostructures and 3D printed systems in terms of their design as drug delivery or tissue engineering devices, their further evaluations and diverse applications. The book highlights the most recent advances in both nanosystems and 3D-printed systems for both drug delivery and tissue engineering applications. It discusses the convergence of biofabrication with nanotechnology, constructing a directional customizable biomaterial arrangement for promoting tissue regeneration, combined with the potential for controlled bioactive delivery. These discussions provide a new viewpoint for both biomaterials scientists and pharmaceutical scientists. Shows how nanotechnology and 3D printing are being used to create systems which are intelligent, biomimetic and customizable to the patient Explores the current generation of nanostructured 3D printed medical devices Assesses the major challenges of using 3D printed nanosystems for the manufacture of new pharmaceuticals

3D Bioprinting: Fundamentals, Principles and Applications provides the latest information on the fundamentals, principles, physics, and applications of 3D bioprinting. It contains descriptions of the various bioprinting processes and technologies used in additive biomanufacturing of tissue constructs, tissues, and organs using living cells. The increasing availability and decreasing costs of 3D printing technologies are driving its use to meet medical needs, and this book provides an overview of these technologies and their integration. Each chapter discusses current limitations on the relevant technology, giving future perspectives. Professor Ozbolat has pulled together expertise from the fields of bioprinting, tissue engineering, tissue fabrication, and 3D printing in his inclusive table of contents. Topics covered include raw materials, processes, machine technology, products, applications, and limitations. The information in this book will help bioengineers, tissue and manufacturing engineers, and medical doctors understand the features of each bioprinting process, as well as bioink and bioprinter types. In addition, the book presents tactics that can be used to select the appropriate process for a given application, such as tissue engineering and regenerative medicine, transplantation, clinics, or pharmaceutics. Describes all aspects of the bioprinting process, from bioink processing through design for bioprinting, bioprinting techniques, bioprinter technologies, organ printing, applications, and future trends Provides a detailed description of each bioprinting technique with an in-depth understanding of its process modeling, underlying physics and characteristics, suitable bioink and cell types printed, and major accomplishments achieved thus far Explains organ printing technology in detail with a step-by-step roadmap for the 3D bioprinting of organs from isolating stem cells to the post-transplantation of organs Presents tactics that can be used to select the appropriate process for a given application, such as tissue engineering and regenerative medicine, transplantation, clinics, or pharmaceutics

3D Printing Applications in Cardiovascular Medicine addresses the rapidly growing field of additive fabrication within the medical field, in particular, focusing on cardiovascular medicine. To date, 3D printing of hearts and vascular systems has been largely reserved to anatomic reconstruction with no additional functionalities. However, 3D printing allows for functional, physiologic and bio-engineering of products to enhance diagnosis and treatment of cardiovascular disease. This book contains the state-of-the-art technologies and studies that demonstrate the utility of 3D printing for these purposes. Addresses the novel technology and cardiac and vascular application of 3D printing Features case studies and tips for applying 3D technology into clinical practice Includes an accompanying website that provides 3D examples from cardiovascular clinicians, imagers, computer science and engineering experts