File Name: introduction to tissue engineering applications and challenges .zip
Tissue engineering is a biomedical engineering discipline that uses a combination of cells , engineering , materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biological tissues. Tissue engineering often involves the use of cells placed on tissue scaffolds in the formation of new viable tissue for a medical purpose but is not limited to applications involving cells and tissue scaffolds. While it was once categorized as a sub-field of biomaterials , having grown in scope and importance it can be considered as a field in its own.
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Now in its fourth edition, Principles of Tissue Engineering has been the definite resource in the field of tissue engineering for more than a decade. As in previous editions, this book creates a comprehensive work that strikes a balance among the diversity of subjects that are related to tissue engineering, including biology, chemistry, material science, and engineering, among others, while also emphasizing those research areas that are likely to be of clinical value in the future. This edition includes greatly expanded focus on stem cells, including induced pluripotent stem iPS cells, stem cell niches, and blood components from stem cells. This research has already produced applications in disease modeling, toxicity testing, drug development, and clinical therapies.
Tissue engineering is a biomedical engineering discipline that uses a combination of cells , engineering , materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biological tissues.
Tissue engineering often involves the use of cells placed on tissue scaffolds in the formation of new viable tissue for a medical purpose but is not limited to applications involving cells and tissue scaffolds.
While it was once categorized as a sub-field of biomaterials , having grown in scope and importance it can be considered as a field in its own. While most definitions of tissue engineering cover a broad range of applications, in practice the term is closely associated with applications that repair or replace portions of or whole tissues i.
Often, the tissues involved require certain mechanical and structural properties for proper functioning. The term has also been applied to efforts to perform specific biochemical functions using cells within an artificially-created support system e.
The term regenerative medicine is often used synonymously with tissue engineering, although those involved in regenerative medicine place more emphasis on the use of stem cells or progenitor cells to produce tissues. A commonly applied definition of tissue engineering, as stated by Langer  and Vacanti,  is "an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve [Biological tissue] function or a whole organ".
Tissue engineering has also been defined as "understanding the principles of tissue growth, and applying this to produce functional replacement tissue for clinical use". Developments in the multidisciplinary field of tissue engineering have yielded a novel set of tissue replacement parts and implementation strategies.
Scientific advances in biomaterials , stem cells, growth and differentiation factors, and biomimetic environments have created unique opportunities to fabricate or improve existing tissues in the laboratory from combinations of engineered extracellular matrices "scaffolds" , cells, and biologically active molecules.
Among the major challenges now facing tissue engineering is the need for more complex functionality, biomechanical stability, and vascularization in laboratory-grown tissues destined for transplantation. In , the NSF published a report entitled "The Emergence of Tissue Engineering as a Research Field", which gives a thorough description of the history of this field. The historic origins of the term are unclear as the definition of the word has changed throughout the past decades.
The term first appeared in a publication that described the organization of an endothelium-like membrane on the surface of a long-implanted, synthetic ophthalmic prosthesis .
The first modern use of the term as recognized today was in by the researcher, physiologist and bioengineer Y. C Fung of the Engineering Research Center. He proposed the joining of the terms tissue in reference to the fundamental relationship between cells and organs and engineering in reference to the field of modification of said tissues.
The term was officially adopted in A rudimentary understanding of the inner workings of human tissues may date back further than most would expect. As early as the Neolithic period, sutures were being used to close wounds and aid in healing. Later on, societies such as ancient Egypt developed better materials for sewing up wounds such as linen sutures. Around BC in ancient India, skin grafts were developed by cutting skin from the buttock and suturing it to wound sites in the ear, nose, or lips.
Ancient Egyptians often would graft skin from corpses onto living humans and even attempted to use honey as a type of antibiotic and grease as a protective barrier to prevent infection. In the 1st and 2nd centuries AD, Gallo-Romans developed wrought iron implants and dental implants could be found in ancient Mayans.
Enlightenment 17th Centuryth Century While these ancient societies had developed techniques that were way ahead of their time, they still lacked a mechanistic understanding of how the body was reacting to these procedures.
This mechanistic approach came along in tandem with the development of the empirical method of science pioneered by Rene Descartes. In the 17th century, Robert Hooke discovered the cell and a letter from Benedict de Spinoza brought forward the idea of the homeostasis between the dynamic processes in the body. Hydra experiments performed by Abraham Trembley in the 18th century began to delve into the regenerative capabilities of cells.
During the 19th century, a better understanding of how different metals reacted with the body led to the development of better sutures and a shift towards screw and plate implants in bone fixation. As time progresses and technology advances, there is a constant need for change in the approach researchers take in their studies. Tissue engineering has continued to evolve over centuries. In the beginning people used to look at and use samples directly from human or animal cadavers.
These advances have allowed researchers to generate new tissues in a much more efficient manner. For example, these techniques allow for more personalization which allow for better biocompatibility, decreased immune response, cellular integration, and longevity. There is no doubt that these techniques will continue to evolve, as we have continued to see microfabrication and bioprinting evolve over the past decade.
In , Wichterle and Lim were the first to publish experiments on hydrogels for biomedical applications by using them in contact lens construction.
Work on the field developed slowly over the next two decades, but later found traction when hydrogels were repurposed for drug delivery. In , Charles Hull developed bioprinting by converting a Hewlett-Packard inkjet printer into a device capable of depositing cells in 2D. So far, scientists have been able to print mini organoids and organs-on-chips that have rendered practical insights into the functions of a human body.
Pharmaceutical companies are using these models to test drugs before moving on to animal studies. A team at University of Utah has reportedly printed ears and successfully transplanted those onto children born with defects that left their ears partially developed. Furthermore, hydrogels in conjunction with 3D bioprinting allow researchers to produce different scaffolds which can be used to form new tissues or organs.
Meanwhile, 3-D printing parts of tissues definitely will improve our understanding of the human body, thus accelerating both basic and clinical research. As defined by Langer and Vacanti,  examples of tissue engineering fall into one or more of three categories: "just cells," "cells and scaffold," or "tissue-inducing factors. Cells are one of the main components for the success of tissue engineering approaches. Examples include fibroblasts used for skin repair or renewal,  chondrocytes used for cartilage repair MACI -FDA approved product , and hepatocytes used in liver support systems.
Cells can be used alone or with support matrices for tissue engineering applications. An adequate environment for promoting cell growth, differentiation, and integration with the existing tissue is a critical factor for cell-based building blocks.
Techniques for cell isolation depend on the cell source. Centrifugation and apheresis are techniques used for extracting cells from biofluids e. Trypsin and collagenase are the most common enzymes used for tissue digestion. While trypsin is temperature dependent, collagenase is less sensitive to changes in temperature. Primary cells are those directly isolated from host tissue. These cells provide an ex-vivo model of cell behavior without any genetic, epigenetic, or developmental changes; making them a closer replication of in-vivo conditions than cells derived from other methods.
These are mature cells, often terminally differentiated, meaning that for many cell types proliferation is difficult or impossible. Additionally, the microenvironments these cells exist in are highly specialized, often making replication of these conditions difficult.
Medium from the primary culture is removed, the cells that are desired to be transferred are obtained, and then cultured in a new vessel with fresh growth medium. Secondary cultures are most notably used in any scenario in which a larger quantity of cells than can be found in the primary culture is desired. Secondary cells share the constraints of primary cells see above but have an added risk of contamination when transferring to a new vessel.
Autologous: The donor and the recipient of the cells are the same individual. Cells are harvested, cultured or stored, and then reintroduced to the host. Autologous cell dependence on host cell health and donor site morbidity may be deterrents to their use. Adipose-derived and bone marrow-derived mesenchymal stem cells are commonly autologous in nature, and can be used in a myriad of ways, from helping repair skeletal tissue to replenishing beta cells in diabetic patients.
Allogenic: Cells are obtained from the body of a donor of the same species as the recipient. While there are some ethical constraints to the use of human cells for in vitro studies ie. Xenogenic: These cells are derived isolated cells from alternate species from the recipient. A notable example of xenogenic tissue utilization is cardiovascular implant construction via animal cells.
Chimeric human-animal farming raises ethical concerns around the potential for improved consciousness from implanting human organs in animals.
Syngenic or isogenic: These cells describe those borne from identical genetic code. This imparts an immunologic benefit similar to autologous cell lines see above. Stem cells are undifferentiated cells with the ability to divide in culture and give rise to different forms of specialized cells. Stem cells are divided into "adult" and "embryonic" stem cells according to their source.
While there is still a large ethical debate related to the use of embryonic stem cells, it is thought that another alternative source-- induced pluripotent stem cells —may be useful for the repair of diseased or damaged tissues, or may be used to grow new organs.
Totipotent cells are stem cells which can divide into further stem cells or differentiate into any cell type in the body, including extra-embryonic tissue. Pluripotent cells are stem cells which can differentiate into any cell type in the body except extra-embryonic tissue. As of November , a popular method is to use modified retroviruses to introduce specific genes into the genome of adult cells to induce them to an embryonic stem cell-like state. Multipotent stem cells can be differentiated into any cell within the same class, such as blood or bone.
A common example of multipotent cells is Mesenchymal stem cells MSCs. Scaffolds are materials that have been engineered to cause desirable cellular interactions to contribute to the formation of new functional tissues for medical purposes. Cells are often 'seeded' into these structures capable of supporting three-dimensional tissue formation.
Scaffolds mimic the extracellular matrix of the native tissue, recapitulating the in vivo milieu and allowing cells to influence their own microenvironments. They usually serve at least one of the following purposes: allow cell attachment and migration, deliver and retain cells and biochemical factors, enable diffusion of vital cell nutrients and expressed products, exert certain mechanical and biological influences to modify the behaviour of the cell phase.
In , an interdisciplinary team led by the thoracic surgeon Thorsten Walles implanted the first bioartificial transplant that provides an innate vascular network for post-transplant graft supply successfully into a patient awaiting tracheal reconstruction. To achieve the goal of tissue reconstruction, scaffolds must meet some specific requirements. High porosity and adequate pore size are necessary to facilitate cell seeding and diffusion throughout the whole structure of both cells and nutrients.
Biodegradability is often an essential factor since scaffolds should preferably be absorbed by the surrounding tissues without the necessity of surgical removal.
The rate at which degradation occurs has to coincide as much as possible with the rate of tissue formation: this means that while cells are fabricating their own natural matrix structure around themselves, the scaffold is able to provide structural integrity within the body and eventually it will break down leaving the newly formed tissue which will take over the mechanical load.
Injectability is also important for clinical uses. Recent research on organ printing is showing how crucial a good control of the 3D environment is to ensure reproducibility of experiments and offer better results. Material selection is an essential aspect of producing a scaffold.
The materials utilized can be natural or synthetic and can be biodegradable or non-biodegradable. The material needed for each application is different, and dependent the desired mechanical properties of the material. Tissue engineering of bone, for example, will require a much more rigid scaffold compared to a scaffold for skin regeneration.
There are a few versatile synthetic materials used for many different scaffold applications. One of these commonly used materials is polylactic acid PLA , a synthetic polymer.
PLA - polylactic acid. This is a polyester which degrades within the human body to form lactic acid , a naturally occurring chemical which is easily removed from the body. This tunability, along with its biocompatibility, makes it an extremely useful material for scaffold creation.
Metrics details. The dynamic nature of modern warfare, including threats and injuries faced by soldiers, necessitates the development of countermeasures that address a wide variety of injuries. Tissue engineering has emerged as a field with the potential to provide contemporary solutions. In this review, discussions focus on the applications of stem cells in tissue engineering to address health risks frequently faced by combatants at war. Human development depends intimately on stem cells, the mysterious precursor to every kind of cell in the body that, with proper instruction, can grow and differentiate into any new tissue or organ. Recent reports have suggested the greater therapeutic effects of the anti-inflammatory, trophic, paracrine and immune-modulatory functions associated with these cells, which induce them to restore normal healing and tissue regeneration by modulating immune reactions, regulating inflammation, and suppressing fibrosis. Therefore, the use of stem cells holds significant promise for the treatment of many battlefield injuries and their complications.
Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. DOI: Birla Published Engineering. Introduction to Tissue Engineering: Applications and Challenges makes tissue engineering more accessible to undergraduate and graduate students alike. It provides a systematic and logical eight-step process for tissue fabrication.
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Introduction to Tissue Engineering: Presents medical applications of stem cells in tissue engineering. Deals with the Request Full-text Paper PDF. To read the.
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Introduction to Tissue Engineering: Applications and Challenges. Author(s). Ravi Birla. First published May Print ISBN |Online.