Organ failure from disease or injury is a major cause of morbidity and mortality for patients. Patients have traditionally been treated with organ transplantation, or artificial support systems that function outside the body (e.g., hemodialysis), but such options suffer from donor shortages, immunocompatibility and rejection issues, and decreased quality of life. This chapter provides an overview of tissue engineering of several important organ systems, including urogenital, liver, lung, gastrointestinal, and pancreatic tissues. Each section provides an insight into the research that has been conducted in the field until now. Although many challenges remain, rapid progress has successfully translated several engineered organs into the clinical setting, while for others, major headway has been made. It is becoming more and more apparent that the future of tissue engineering and regenerative medicine is intimately intertwined and that their clinical translation relies on our increasing knowledge of biomaterials and their interaction with living cells.
The goal of tissue engineering (TE) is to engineer suitable microenvironments for the regeneration of tissues or organs. To accomplish this objective, many engineering technologies have been adopted to create well-defined three-dimensional architectures at physiologically relevant length scales. This chapter reviews microfabrication technologies that are actively employed in various TE applications, including photolithography, soft-lithography, and microfluidics. In addition, strategies to assemble microtissues into hierarchical constructs are also discussed.
This chapter will cover the three main classes of synthetic biomaterial that undergo biodegradation process in vivo and have been utilized in scaffold fabrication. These are namely bioceramics (e.g., calcium phosphate compounds), polymers (e.g., aliphatic polyesters) and biometals (e.g., magnesium alloys). For each class of biomaterials, details will be provided on the degradation mechanism and the specific factors that influence degradation, including microstructural/compositional features of the biomaterials itself, as well as environmental factors. Degradation evaluation methods will be considered including both in vitro and in vivo methodologies.
The burden of cardiovascular pathologies, such as heart failure after myocardial infarction or due to congenital heart defects, is still very high. Existing clinical therapies for these life-threatening conditions cannot regenerate and restore tissue function and provide mainly palliative treatment. This critical drawback has fueled the development of novel technologies aimed to repair or replace damaged heart tissue and correct heart defects. Such strategies, broadly termed “cardiovascular tissue engineering,” are a direct result of collaboration between researchers from various fields, such as material science, engineering, cardiovascular biology, and medicine. This chapter offers an overview of such multidisciplinary strategies, emphasizing the various concepts and major applications. The chapter could be of interest not only from an educational perspective, but also for researchers and medical professionals, offering a fresh view on novel and powerful treatment options based on tissue engineering and regeneration.
The creation or modification of materials using synthetic methods has provided a longstanding approach to customizable biomaterials. The rational design of properties and functionalities is a major advantage of synthetic methodologies, while the bioactivity and resorption are challenges. This chapter will introduce synthetic approaches toward the creation of designer biomaterials, major breakthroughs in the field, and major challenges upcoming. We will take a synthetic/polymeric view of the field of biomaterials. Metals will be left out mostly due to their nonbiological nature.
Cell–material interactions are critical to the success of tissue engineering strategies. Cells interact with and interpret physical and functional parameters of their environment, leading to rapid responses that influence cell form, function, and fate decision-making. Tissue engineering strategies can tune properties of the material interface, such as chemistry (ligand availability, charge), mechanics (stiffness and viscosity), and topography (architecture), to produce scaffolds or devices that are highly biomimetic. Cells sense and respond to these mechanical stimuli from the material through the extracellular matrix and adhesion receptors such as integrins, in a process termed mechanotransduction. In this chapter, we will first discuss the process of how cells adhere to and interact with materials and then how modulation of material properties permits tissue engineers precise control of cell–material interactions and thus cellular responses, including tuneable surfaces to control processes such as cell attachment, signaling, migration, and phenotype. Understanding cell–material interactions will allow for the development of novel tissue engineering strategies for clinically relevant applications, and as tools for investigating important cellular processes.
This chapter gives a general overview on the third edition of the Tissue Engineering book. It comprises the general components of the book as an educational tool and whom it was written for (the readers). The book discusses the tissue engineering origins, limitations, and promises to move the field forward, a field that is inherently interdisciplinary. Furthermore, this chapter defines the attitude tissue engineers in-training need to have to adsorb and apply concepts and principles in their own research. This chapter ends with a detailed recommendation on how to use each chapter, as it possesses many educational tools that will maximize the learning and teaching experience.
This chapter gives a general overview on the basic requirements for designing bioreactors for tissue engineering. It comprises the general components of a bioreactor and discusses the choice of suitable culture parameters for a tissue engineering process. Furthermore, the necessity to mimic physiologic conditions with the help of bioreactor systems in order to achieve sufficient tissue maturation is explained. As cell expansion is a prerequisite for tissue engineering processes, this chapter covers also bioreactors for expansion of cells and the issue of scale-up versus scale-out. Finally, commercially available bioreactor systems for the application of defined mechanical forces for tissue engineering processes are presented and discussed.
The materials that are employed in regenerative medicine and tissue engineering applications often react unfavorably in vivo (induce clotting, promote bacterial infection, stimulate a foreign body immune response). There is a need to develop new materials that generate specific cell responses, but how is this best achieved considering the huge number of materials that could be synthesized? This chapter is a description of how materials discovery can be effectively carried out using both high throughput screening and computational modeling approaches. We define and describe the components of these approaches, highlighting the most important points of consideration, with the aim of providing a starting point for new biomaterial researchers.
Manufacturing of a tissue-engineered product (TEP) is an essential part of the road from “lab to patient,” with its own set of challenges which are different from those covered in other chapters of this book. In manufacturing, TEP quality is the main consideration, and this is also reflected in the regulatory framework facilitating the commercial manufacturing of these products, ensuring their safety and efficacy for patients. This regulatory framework specifies most of the technical demands that the manufacturing process needs to meet, which are often underdeveloped when the TEP enters preclinical phases. Thus, a certain amount of process development is still needed, and existing strategies allow to do this efficiently and effectively. Besides quality, there are other important considerations such as process scalability and manufacturing cost. From these perspectives, a lot of attention is being devoted in recent years to next-generation processes which are automated, utilize single-use equipment, and rely on mathematical process models for efficient process development and effective process monitoring and control.
The success of engineered tissues after their implantation strongly depends on the rapid establishment of an efficient vascular network throughout the implant, ensuring its long-term viability and functionality. Tremendous effort has been dedicated to exploring ways to promote the neo-vascularization of three-dimensional (3D) engineered tissue implants. Here, we present an overview of different relevant approaches. This chapter includes the description of in vitro strategies used to promote vascular ingrowth from the host tissue as well as methods to increase cellular viability within 3D constructs or ways to produce a vascular network before implantation. We further present ex vivo and in vivo techniques for the assessment of vascular growth and engraftment of the implants. Finally, we discuss the limitations of the current approaches and potential future directions.
The mechanism by which cells receive and respond to stimuli is known as cell signaling. By understanding the fundamentals of cell signaling, tissue engineers can better direct cell behavior. This chapter outlines the paradigm of cell signaling, from signal initiation to signal transduction to gene activation. The main types of signals, receptors, and the machinery for gene activation are described and specific signaling cascades relevant to tissue engineering are outlined. For example, the G-protein–coupled receptors and the receptor tyrosine kinases are detailed, as are the TGF-β superfamily, Wnt signaling, Rho kinase signaling, NF-κB signaling, and vitamin D signaling. The complexity of cellular signaling is underlined with examples of where it deviates from the classical descriptions of these pathways. Throughout this chapter, various means for tissue engineers to exploit these pathways to direct cell behavior are revealed. And finally, a future perspective about how tissue engineering will continue to benefit from advances in cell signaling is given.
In pathologies where there is large skin loss and damage like burns and chronic ulcers, successful treatment is dependent on prompt excision followed by early wound coverage to increase survival rates. The field of skin engineering for the treatment of such acute and chronic wounds has expanded over the last 30 years due to increased knowledge gained and technical advances in the areas of molecular and cellular biology. This chapter focuses on skin biology, keratinocyte culture, and grafting, the latter of which has led to the production of epidermal replacements and the need for a dermal layer for permanent wound closure. Subsequently, the development of dermal template products and cultured skin substitutes are discussed with emphasis being placed on their biological relevance to wound healing. The clinical application of keratinocyte stem cells and the potential use of other adult stem cells in skin tissue engineering are also discussed.
The formation of functional organs and tissues during embryonic development is a complex process involving multiple cell types derived from ectoderm, mesoderm, endoderm, and the neural crest. These cell types interact via diverse mechanisms. Examples of such mechanisms are direct cell–cell contacts and paracrine signaling by morphogenic gradients. Cell behavior during organogenesis is dynamic and is dependent on cell movements of a subset of cells. Other cells revert their phenotype by a process called epithelial-to-mesenchyme transition and may become migratory. To obtain functional organs, cells respond to environmental signals like pulsatile blood flow by activation of adaptive signaling mechanisms, which direct tissue architecture. The timely, proper dosing and sequential integration of all these elements during organogenesis specifies cell types and shapes the organ's form and function in the embryo. Tissue engineering relies on reiteration of these developmental processes and aims to combine this knowledge with typical engineering disciplines to generate functional substitutes to replace lost or worn out tissue. This process is known as developmental (re)engineering.
This chapter discusses mammalian extracellular matrix (ECM) as a biologic scaffold material for tissue engineering applications. ECM has been used as a surgically implantable bioscaffold for the reconstruction of injured or missing tissues. Biologic scaffolds composed of ECM alter the default mammalian injury response and promote constructive and functional tissue remodeling. This chapter reviews ECM bioscaffold preparation and mechanisms of action. Commercially available ECM bioscaffolds and recent clinical applications are also discussed.
This chapter deals with the tissue engineering aspects of the mesenchymal tissues—cartilage and bone. It includes a brief description of the tissue types and their embryonal origin. Tissue structures including cell and extracellular matrix components are described in detail. The disease aspect of hyaline cartilage with emphasis on cartilage injuries and the tissue engineering approach to cartilage regeneration with the autologous chondrocyte implantation technique is described in depth. Bone fracture healing and biomaterials for bone repair is also described in depth. The future aspects of tissue regeneration techniques with potential cell types including stem cells as well as new promising scaffold techniques are described.
The nervous system is the most important system of the body and damaging this system could be lethal for humans. Restoring the function of a damaged nervous system has always been a challenge due to the complexity of this system and its limited ability of regeneration. Furthermore, several obstacles exist in the repair process of the nervous system. In the central nervous system (CNS) limited clearance of myelin and formation of inhibitory glial scars make regeneration difficult. There is no effective clinical treatment for damages in the CNS while current treatments focus on stabilization and prevention of further damage and consequently on rehabilitation and preparation of prosthetics and mechanical aids. In peripheral nervous system (PNS) damages, the management may be a nerve autograft or allograft while shortage of donors for nerves makes the situation difficult. Size inequality between the donor nerve and the recipient, danger of neuroma formation, and occurrence of infectious diseases are other problems associated with PNS, while indeed complete recovery of function is still not common. Several studies have illustrated that implying tissue engineering strategies for neural repair may lead to considerable improvements in damaged nervous tissues.
