[PDF] Bioactive And Mechanical Stimuli For Engineering Neocartilage With Native Tissue Like Tensile Properties eBook

Author : Jennifer K. Lee
Publisher :
Page : pages
File Size : 46,97 MB
Release : 2015
Category :
ISBN : 9781339542966

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Tissue engineering aims to recapitulate native tissue function to replace diseased or damaged tissues. Scaffold-free techniques such as the self-assembling process have recently emerged to exploit the natural synthetic ability of cells. Our group, in particular, has used the self-assembling process to engineer various neocartilages including femoral cartilage, the knee meniscus, and the temporomandibular joint disc. For those suffering from degenerative cartilage diseases of the joints, tissue engineered cartilage may prove a viable solution bridging early palliative treatments like microfracture and end-stage irreversible options like total joint replacement. Though we have extensive experience with the self-assembling process, the mechanisms of self-assembly are not well understood. The first global objective of this thesis thus focused on elucidating self-assembly mechanisms, toward developing rational agents to influence the process. The second global objective of this thesis sought to enhance neocartilage tensile properties through the application of novel bioactive stimuli that mimic the osmotic and developmental milieu of articular cartilage. The final objective of this work aimed to engineer--for the first time--articular cartilage with functional native tissue-like tensile stiffness, strength, and anisotropy, through the application of tensile stimulation. To address these objectives, this thesis 1) elucidated the roles of cadherins and integrins in mediating the self-assembling process, 2) explored the effects of controlling the cellular osmotic environment on functional properties of self-assembled articular chondrocytes, 3) evaluated the use of developmentally critical thyroid hormones to increase neocartilage properties, and 4) investigated the application of tensile mechanical stimulation to enhance anisotropy and tensile properties of neocartilage and explored the in vivo stability of tensile properties. The results of this work include a proposed mechanism of self-assembly, mediated by cell-cell and cell-matrix adhesion molecules and with a functional cytoskeletal network. Both integrins and cadherins were found to influence the self-assembling process, with integrin-based self-assembly dominating in the presence of surface-bound collagen molecules. Neocartilage generated in the absence of surface-bound collagen was found to exhibit significantly up-regulated collagen production. Finally, it was shown that both an intact myosin-actin network and mediators of contractility (i.e., Rho kinase) are crucial to facilitating robust self-assembly. This work also demonstrated that recapitulation of the native tissue microenvironment enhanced neocartilage functional properties. Modulation of the osmotic environment via application of a physiologically relevant level of calcium, hyperosmolarity, and a calcium channel agonist were found to beneficially interact, yielding increases in tensile stiffness. Rationally deriving additional stimuli from the development of growth plate cartilage--specifically, thyroid hormones parathyroid hormone, tri-iodothyronine (T3), and thyroxine (T4)--allowed us to engineer neocartilage exhibiting a tensile stiffness nearly 4-times that of untreated control values. T3, however, is known to elicit hypertrophic responses in growth plate chondrocytes, an undesirable phenotype in neocartilage. Sequential application of T3 and PTH in this work resulted in reduced hypertrophic responses while maintaining the enhanced tensile properties. Finally, application of a tensile stimulation regimen, in combination with matrix enhancing agents TGF-[beta]1, chondroitinase-ABC, and lysyl oxidase-like protein 2, resulted in scaffold-free neocartilage with tensile properties that, for the first time, are on par with native tissues. Moreover, this work established that tensile stimulation increases expression of matrix remodeling enzymes, the BMP2/SMAD7 signaling pathway, and cell-matrix interactions via integrins. Function of the calcium channel transient receptor potential vanilloid 4 was found to be responsible for mechanotransduction of tensile stimulation. Finally, implantation of treated neocartilages demonstrated maintenance or increases in functional properties. Collectively, this work elucidated the mechanisms of scaffold-free self-assembly, enabling future work to rationally select agents to beneficially impact this process. Through the application of 1) bioactive stimuli guided by the native osmotic microenvironment and by developmental biology, and 2) a novel tensile stimulation regimen, this thesis achieved tensile properties on par with native articular cartilage. These functional neocartilages can ultimately be used to replace damaged or diseased tissues to restore joint function.

Author : Le W. Huwe
Publisher :
Page : pages
File Size : 20,82 MB
Release : 2017
Category :
ISBN : 9780355149418

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Articular cartilage degeneration, due to injury and osteoarthritis, is an irreversible disease condition with existing treatment options. Damaged cartilage in the patellofemoral and temporomandibular joints are met with unsatisfactory treatment options that often fail to halt the disease progression. Tissue engineering aims to solve this unmet need by engineering a functional replacement tissue as well as by promoting a healthy regenerative environment within the damaged joint. A key component in engineering neocartilage with such properties is the cell source. Costal chondrocytes of the rib cage have recently been recognized for their ability to form robust cartilage implants. However, clinical translation of this cell source is still hindered because mechanical properties of the engineered implants need to be improved, and treatment with the engineered implant needs to be demonstrated in an appropriate preclinical model. Toward translating tissue engineering technologies to clinical applications, the global objectives of this research are: 1) to engineer biomimetic cartilage implants from costal chondrocytes, through the development of mechanical stimulation techniques, and 2) to evaluate the safety and efficacy of engineered cartilage implants orthotopically in a relevant large animal model. To address these objectives, this research 1) confirmed costal chondrocytes, of non-articular cartilage origin, to be appropriate for use in articular joints, 2) designed and developed compressive stimulation regimens that improved the compressive properties of neocartilage, 3) designed and developed tensile stimulation regimens that enhanced the tensile properties and anisotropy of neocartilage, and 4) investigated the safety and efficacy of neocartilage in healing an orthotopic defect in a minipig model. Costal chondrocytes were confirmed to be suitable for articular cartilage tissue engineering. Costal cartilage is densely populated with chondrocytes, rendering a good donor source of cells. Neocartilage derived from passaged costal chondrocytes, through the self-assembling process, were cohesive and robust. When compared to the native articular cartilage of the patellofemoral joint for their potential as a replacement tissue, the implants exhibited 45% of native cartilage salient properties. These results indicated that costal chondrocytes are suitable for articular cartilage tissue engineering, with the potential for further improvement with mechanical stimulation. Neocartilage derived from costal chondrocytes was shown for the first time to respond to mechanical stimulation, in particular, the passive axial compressive stimulation. During the self-assembling process, neocartilage in the matrix synthesis phase and maturation phase are amenable to passive axial compression, providing flexibly in the timing of the stimulation. When compressive magnitude was examined, 3.3 kPa and 5 kPa were found efficacious in improving neocartilage compressive properties. Stimulation with a higher magnitude was found ineffective. Neocartilage tensile properties were improved through the application of a bioactive regimen (TGF-[beta]1, chondroitinase ABC, and lysyl oxidase like 2). This work demonstrated that mechanical and bioactive stimuli are both critical in creating mechanically robust neocartilage from costal chondrocytes. Further improvements in tensile properties were achieved with tensile stimulation. A beneficial tensile stimulation regimen has not been achieved in prior studies; this work showed for the first time that tensile stimulation, especially continuous tensile stimulation, was highly effective in creating neocartilage with native tissue-like tensile properties. Anisotropy was also achieved with this stimulation. Therefore, this research contributed significantly toward overcoming two of the major challenges posed by cartilage tissue engineering. The examination of this regimen in a human chondrocyte-derived neocartilage also showed that tensile stimulation was beneficial toward neocartilage development and mechanical robustness, demonstrating the translation potential of this stimulation regimen. Finally, robust neocartilage implants, derived from costal chondrocytes and improved through mechanical and bioactive stimuli, showed safety and efficacy when examined orthotopically in a large animal model. A novel surgical technique, called the intra-laminar fenestrated technique, was successfully developed and implemented to model TMJ disc thinning in vivo. Neocartilage implants, of allogeneic origin, did not provoke any adverse immunological response from the host. They were effective in promoting repair tissue formation in the defect and integration between implant and native tissue, resulting in closing and healing of the defect. Overall, this research made strides in bringing tissue engineered neocartilage implants from a clinically relevant cell source toward a translational pathway. The successful engineering of implants and demonstrated treatment of an orthotopic defect established the foundational work for future preclinical studies. With further research, scaffold-free tissue engineered implants could significantly widen clinical treatment options for patients suffering from patellofemoral and temporomandibular joint degeneration.

Author : Valentina Di Felice
Publisher : Frontiers Media SA
Page : 92 pages
File Size : 34,9 MB
Release : 2016-05-18
Category : Physiology
ISBN : 2889198413

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Tissue engineering is an innovative, multidisciplinary approach which combines (bio)materials, cells and growth factors with the aim to obtain neo-organogenesis to repair or replenish damaged tissues and organs. The generation of engineered tissues and organs (e. g. skin and bladder) has entered into the clinical practice in response to the chronic lack of organ donors. In particular, for the skeletal and cardiac muscles the translational potential of tissue engineering approaches has clearly been shown, even though the construction of this tissue lags behind others given the hierarchical, highly organized architecture of striated muscles. Cardiovascular disease is the leading cause of death in the developed world, where the yearly incidence of Acute MI (AMI) is approx 2 million cases in Europe. Recovery from AMI and reperfusion is still less than ideal. Stem cell therapy may represent a valid treatment. However, delivery of stem cells alone to infarcted myocardium provides no structural support while the myocardium heals, and the injected stem cells do not properly integrate into the myocardium because they are not subjected to the mechanical forces that are known to drive myocardial cellular physiology. On the other hand, there are many clinical cases where the loss of skeletal muscle due to a traumatic injury, an aggressive tumour or prolonged denervation may be cured by the regeneration of this tissue. In vivo, stem or progenitor cells are sheltered in a specialized microenvironment (niche), which regulates their survival, proliferation and differentiation. The goal of this research topic is to highlight the available knowledge on biomaterials and bioactive molecules or a combination of them, which can be used successfully to differentiate stem or progenitor cells into beating cardiomyocytes or organized skeletal muscle in vivo. Innovations compared to the on-going trials may be: 1) the successful delivery of stem cells using sutural scaffolds instead of intracoronary or intramuscular injections; 2) protocols to use a limited number of autologous or allogeneic stem cells; 3) methods to drive their differentiation by modifying the chemical-physical properties of scaffolds or biomaterials, incorporating small molecules (i.e. miRNA) or growth factors; 4) methods to tailor the scaffolds to the elastic properties of the muscle; 5) studies which suggest how to realize scaffolds that optimize tissue functional integration, through the combination of the most up-to-date manufacturing technologies and use of bio-polymers with customized degradation properties.

Author : Anwarul Hasan
Publisher : John Wiley & Sons
Page : 762 pages
File Size : 26,88 MB
Release : 2017-06-19
Category : Science
ISBN : 3527338632

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A comprehensive overview of the latest achievements, trends, and the current state of the art of this important and rapidly expanding field. Clearly and logically structured, the first part of the book explores the fundamentals of tissue engineering, providing a separate chapter on each of the basic topics, including biomaterials stem cells, biosensors and bioreactors. The second part then follows a more applied approach, discussing various applications of tissue engineering, such as the replacement or repairing of skins, cartilages, livers and blood vessels, to trachea, lungs and cardiac tissues, to musculoskeletal tissue engineering used for bones and ligaments as well as pancreas, kidney and neural tissue engineering for the brain. The book concludes with a look at future technological advances. An invaluable reading for entrants to the field in biomedical engineering as well as expert researchers and developers in industry.

Author : Kishor Kumar Sadasivuni
Publisher : Elsevier
Page : 546 pages
File Size : 47,20 MB
Release : 2016-09-10
Category : Science
ISBN : 0081009747

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Biopolymer Composites in Electronics examines the current state-of-the-art in the electronic application based on biopolymer composites. Covering the synthesis, dispersion of fillers, characterization and fabrication of the composite materials, the book will help materials scientists and engineers address the challenges posed by the increased use of biopolymeric materials in electronic applications. The influence of preparation techniques on the generation of micro, meso, and nanoscale fillers, and the effect of filler size and dispersion on various biopolymers are discussed in detail. Applications covered include sensors, actuators, optics, fuel cells, photovoltaics, dielectrics, electromagnetic shielding, piezoelectrics, flexible displays, and microwave absorbers. In addition, characterization techniques are discussed and compared, enabling scientists and engineers to make the correct choice of technique. This book is a ‘one-stop’ reference for researchers, covering the entire state-of-the-art in biopolymer electronics. Written by a collection of expert worldwide contributors from industry, academia, government, and private research institutions, it is an outstanding reference for researchers in the field of biopolymer composites for advanced technologies. Enables researchers to keep up with the rapid development of biopolymer electronics, which offer light, flexible, and more cost-effective alternatives to conventional materials of solar cells, light-emitting diodes, and transistors Includes thorough coverage of the physics and chemistry behind biopolymer composites, helping readers to become rapidly acquainted with the fiel Provides in-depth information on the range of biopolymer applications in electronics, from printed flexible conductors and novel semiconductor components, to intelligent labels, large area displays, and solar panels

Author : Kyriacos A. Athanasiou
Publisher : CRC Press
Page : 442 pages
File Size : 35,32 MB
Release : 2013-03-21
Category : Medical
ISBN : 143985324X

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Well-known for their inability to heal, articular cartilage injuries often degenerate inexorably to disastrous impairment. Multitudes of treatments have been devised for this problem, but no satisfactory long-term solutions have been established. Written by world-class experts, Articular Cartilage covers the latest research and advancements related to biology, development, pathology, clinical applications, and tissue engineering. This book is useful for rheumatologists, orthopaedic surgeons, cartilage biologists, and cartilage engineers as well as for professionals working in the orthopaedic and other musculoskeletal industries. This book also belongs in the library of primary care physicians, gerontologists, physical therapists, kinesiologists, and chiropractors. Written at a level that allows accessibility to a wide audience, it provides an interdisciplinary approach that encompasses the breadth and depth of basic science, bioengineering, translational science, and detailed methodologic approaches. The authors examine the major events and signaling molecules that lead to development of articular cartilage from precursor cells, and the changes in cartilage as it matures and ages. They focus on the epidemiology, etiopathogenesis, and therapeutic approaches for cartilage injury and the major arthritides that affect cartilage and the synovial joints such as osteoarthritis, rheumatoid arthritis, and gout. They supply an up-to-date overview of the field of tissue engineering as applied to articular cartilage repair. They examine a number of methods used to assess structure, composition, biology, and biomechanical function. Each chapter contains extensive references to enhance additional study. The book’s comprehensive focus on multiple aspects of articular cartilage sets it apart from other tissue engineering or developmental biology-based books available. It includes important discussions and perspectives on many of the remaining challenges and opportunities in the development and translation of new approaches for treating diseases of articular cartilage. It also provides detailed working protocols for many of the methods used to study articular cartilage, coverage of current treatment options, and business and regulatory aspects of the development of cartilage products. It provides a deeper understanding that will help with the development of new products and clinical applications.

Author : Kyriacos A. Athanasiou
Publisher : Morgan & Claypool Publishers
Page : 183 pages
File Size : 32,84 MB
Release : 2010
Category : Medical
ISBN : 1598298755

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Cartilage injuries in children and adolescents are increasingly observed, with roughly 20% of knee injuries in adolescents requiring surgery. In the US alone, costs of osteoarthritis (OA) are in excess of $65 billion per year (both medical costs and lost wages). Comorbidities are common with OA and are also costly to manage. Articular cartilage's low friction and high capacity to bear load makes it critical in the movement of one bone against another, and its lack of a sustained natural healing response has necessitated a plethora of therapies. Tissue engineering is an emerging technology at the threshold of translation to clinical use. Replacement cartilage can be constructed in the laboratory to recapitulate the functional requirements of native tissues. This book outlines the biomechanical and biochemical characteristics of articular cartilage in both normal and pathological states, through development and aging. It also provides a historical perspective of past and current cartilage treatments and previous tissue engineering efforts. Methods and standards for evaluating the function of engineered tissues are discussed, and current cartilage products are presented with an analysis on the United States Food and Drug Administration regulatory pathways that products must follow to market. This book was written to serve as a reference for researchers seeking to learn about articular cartilage, for undergraduate and graduate level courses, and as a compendium of articular cartilage tissue engineering design criteria. Table of Contents: Hyaline Articular Cartilage / Cartilage Aging and Pathology / In Vitro / Bioreactors / Future Directions

Author : Aleksandr Ovsianikov
Publisher : Springer
Page : 0 pages
File Size : 18,3 MB
Release : 2018-06-08
Category : Science
ISBN : 9783319454436

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This volume provides an in-depth introduction to 3D printing and biofabrication and covers the recent advances in additive manufacturing for tissue engineering. The book is divided into two parts, the first part on 3D printing discusses conventional approaches in additive manufacturing aimed at fabrication of structures, which are seeded with cells in a subsequent step. The second part on biofabrication presents processes which integrate living cells into the fabrication process.

Author : Kyriacos A. Athanasiou
Publisher : CRC Press
Page : 442 pages
File Size : 45,69 MB
Release : 2017-01-06
Category : Medical
ISBN : 1351722328

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Well-known for their inability to heal, articular cartilage injuries often degenerate inexorably to disastrous impairment. Multitudes of treatments have been devised for this problem, but no satisfactory long-term solutions have been established. Written by world-class experts, Articular Cartilage covers the latest research and advancements related to biology, development, pathology, clinical applications, and tissue engineering. This book is useful for rheumatologists, orthopaedic surgeons, cartilage biologists, and cartilage engineers as well as for professionals working in the orthopaedic and other musculoskeletal industries. This book also belongs in the library of primary care physicians, gerontologists, physical therapists, kinesiologists, and chiropractors. Written at a level that allows accessibility to a wide audience, it provides an interdisciplinary approach that encompasses the breadth and depth of basic science, bioengineering, translational science, and detailed methodologic approaches. The authors examine the major events and signaling molecules that lead to development of articular cartilage from precursor cells, and the changes in cartilage as it matures and ages. They focus on the epidemiology, etiopathogenesis, and therapeutic approaches for cartilage injury and the major arthritides that affect cartilage and the synovial joints such as osteoarthritis, rheumatoid arthritis, and gout. They supply an up-to-date overview of the field of tissue engineering as applied to articular cartilage repair. They examine a number of methods used to assess structure, composition, biology, and biomechanical function. Each chapter contains extensive references to enhance additional study. The book’s comprehensive focus on multiple aspects of articular cartilage sets it apart from other tissue engineering or developmental biology-based books available. It includes important discussions and perspectives on many of the remaining challenges and opportunities in the development and translation of new approaches for treating diseases of articular cartilage. It also provides detailed working protocols for many of the methods used to study articular cartilage, coverage of current treatment options, and business and regulatory aspects of the development of cartilage products. It provides a deeper understanding that will help with the development of new products and clinical applications.

Author : Farshid Guilak
Publisher : Springer Science & Business Media
Page : 434 pages
File Size : 25,57 MB
Release : 2003-07-09
Category : Science
ISBN : 0387955534

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-Softcover reprint of a successful hardcover reference (370 copies sold) -Price to be accessible to the rapidly increasing population of students and investigators in the field of tissue engineering -Chapters written by well-known researchers discuss issues in functional tissue engineering as well as provide guidelines and a summary of the current state of technology