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Uncovering Biological Mechanisms of Immunomodulatory Biomaterials for Encapsulated Cell Therapies

Uncovering Biological Mechanisms of Immunomodulatory Biomaterials for Encapsulated Cell Therapies PDF Author: Amanda L. Facklam
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

Book Description
Biomaterials are used in a variety of therapeutics including vaccines, engineered tissues, and cell therapies. Biomaterials enable a range of functionalities such as localized delivery, sustained release, and responsiveness. In the context of cell therapies, biomaterials can protect encapsulated cells from immune attack while allowing for nutrient and oxygen exchange. While this approach holds greats potential, the immune response to biomaterials remains a major challenge to the field. Upon implantation of a material, the immune system will initiate the foreign body response, a cascade of inflammatory activity resulting in material fibrosis. For encapsulated cell therapies, biomaterial fibrosis can result in diminished cell functionality or even cell death. To address this challenge, it is critical to design biomaterials which can modulate the host immune response to mitigate fibrosis. In this thesis, we characterize the effect of biomaterial properties on immune responses after implantation. First, we describe how physical properties of alginate capsules can affect the success of encapsulated cell therapy. We find that capsules with lower permeability to IgG and higher strength enable longer encapsulated islet cures in diabetic mice. Furthermore, we show that differences in islet cure lengths were largely dependent on differential capsule immune responses. Next, we describe the effects of E9, an anti-fibrotic biomaterial coating, on macrophage behavior. We find that E9 downregulates CD86 surface expression when immobilized on a biomaterial surface. In addition, E9 downregulates the secretion of several cytokines including MCP-1 and VEGF and upregulates the secretion of IL-1[beta] from macrophages. Next, we describe our work identifying the functional protein targets of E9 to gain further insight into its mechanism of action. We find that Macrophage migration inhibitory factor and Thioredoxin bind E9 and may have roles in its anti-fibrotic activity. Through this work, we identify macrophage proteins and signaling pathways involved in the mechanism of action of E9, leading to an improved understanding of the foreign body response. Overall, by characterizing the effect of material properties on immune responses, we enable rational design of next-generation immunomodulatory biomaterials.

Uncovering Biological Mechanisms of Immunomodulatory Biomaterials for Encapsulated Cell Therapies

Uncovering Biological Mechanisms of Immunomodulatory Biomaterials for Encapsulated Cell Therapies PDF Author: Amanda L. Facklam
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

Book Description
Biomaterials are used in a variety of therapeutics including vaccines, engineered tissues, and cell therapies. Biomaterials enable a range of functionalities such as localized delivery, sustained release, and responsiveness. In the context of cell therapies, biomaterials can protect encapsulated cells from immune attack while allowing for nutrient and oxygen exchange. While this approach holds greats potential, the immune response to biomaterials remains a major challenge to the field. Upon implantation of a material, the immune system will initiate the foreign body response, a cascade of inflammatory activity resulting in material fibrosis. For encapsulated cell therapies, biomaterial fibrosis can result in diminished cell functionality or even cell death. To address this challenge, it is critical to design biomaterials which can modulate the host immune response to mitigate fibrosis. In this thesis, we characterize the effect of biomaterial properties on immune responses after implantation. First, we describe how physical properties of alginate capsules can affect the success of encapsulated cell therapy. We find that capsules with lower permeability to IgG and higher strength enable longer encapsulated islet cures in diabetic mice. Furthermore, we show that differences in islet cure lengths were largely dependent on differential capsule immune responses. Next, we describe the effects of E9, an anti-fibrotic biomaterial coating, on macrophage behavior. We find that E9 downregulates CD86 surface expression when immobilized on a biomaterial surface. In addition, E9 downregulates the secretion of several cytokines including MCP-1 and VEGF and upregulates the secretion of IL-1[beta] from macrophages. Next, we describe our work identifying the functional protein targets of E9 to gain further insight into its mechanism of action. We find that Macrophage migration inhibitory factor and Thioredoxin bind E9 and may have roles in its anti-fibrotic activity. Through this work, we identify macrophage proteins and signaling pathways involved in the mechanism of action of E9, leading to an improved understanding of the foreign body response. Overall, by characterizing the effect of material properties on immune responses, we enable rational design of next-generation immunomodulatory biomaterials.

Recent Advancements of Immunomodulatory Biomaterials in Cell Therapy and Tissue Engineering

Recent Advancements of Immunomodulatory Biomaterials in Cell Therapy and Tissue Engineering PDF Author: Sudip Mukherjee
Publisher: Springer
ISBN: 9783031508431
Category : Technology & Engineering
Languages : en
Pages : 0

Book Description
This book presents the recent developments in immunomodulatory biomaterials for cell-based therapies in various diseases, including diabetes, cancer, cardiovascular disease, and bone regeneration. The authors first cover the fundamentals of conventional immunology and immunomodulation, before focusing on the history, advantages, and challenges of cell therapies. Biological cell therapy has gained immense attention for various diseases due to unique advantages it has over chemical drugs regarding cost, ease of production, toxicity, and therapeutic efficacy. However, these cell-based therapies need an inert delivery system that can locally deliver cells and minimally elicit foreign body response. The book discusses the foreign body response to the immunomodulatory biomaterials as well as the current and future strategies for potential mitigation of considerable immune responses toward immunomodulatory biomaterials and devices.

Immunomodulatory Biomaterials

Immunomodulatory Biomaterials PDF Author: Stephen F. Badylak
Publisher: Woodhead Publishing
ISBN: 0128214562
Category : Technology & Engineering
Languages : en
Pages : 296

Book Description
Biomaterials have existed for millennia as mechanical replacement structures following disease or injury. Biomaterial design has changed markedly from structural support with an "inert immune profile as the primary objective to designs that elicit an integrative local tissue response and a pro-repair immune cell phenotype. Immunomodulatory Biomaterials: Regulating the Immune Response with Biomaterials to Affect Clinical Outcome offers a single, comprehensive reference on biomaterials for modulation of the host response, for materials scientists, tissue engineers and those working in regenerative medicine. This book details methods, materials and strategies designed to regulate the host immune response following surgical implantation and thus facilitate specific local cell infiltration and tissue deposition. There has been a dramatic transformation in our understanding of the role of the immune system, both innate and adaptive; these changes include recognition of the plasticity of immune cells, especially macrophages, cross-talk between the immune system and stem cells, and the necessity for in situ transition between inflammatory and regulatory immune cell phenotypes. The exploitation of these findings and the design and manufacture of new biomaterials is occurring at an astounding pace. There is currently no book directed at the interdisciplinary principles guiding the design, manufacture, testing, and clinical translation of biomaterials that proactively regulate the host tissue immune response. The challenge for academia, industry, and regulatory agencies to encourage innovation while assuring safety and maximizing efficacy has never been greater. Given the highly interdisciplinary requirements for the design, manufacture and use of immunomodulatory biomaterials, this book will prove a useful single resource across disciplines. - Holistically covers the design, manufacture, testing, and clinical translation of biomaterials that proactively regulate the host tissue immune response - Provides a single reference for understanding and utilizing the host response in biomaterials design - An international collaboration of leading researchers in the field offering a novel insight into this fast-growing area

Cell Microencapsulation

Cell Microencapsulation PDF Author: Emmanuel C. Opara
Publisher: Humana
ISBN: 9781493963621
Category : Science
Languages : en
Pages : 0

Book Description
This volume provides a unique forum to review cell microencapsulation in a broad sense by exploring various cell types that have been encapsulated for different purposes, different approaches and devices used for microencapsulation, the biomaterials used in cell microencapsulation, the challenges to the technology, and the current status of its application in different clinical situations. This book is divided in five sections: Section I is an introductory part that discusses historical developments of the technology and its current challenges, as well as the various applications of cell microencapsulation; Section II discusses the main approaches and devices currently used in cell microencapsulation; Section III presents an overview of the various polymeric materials currently in use for cell microencapsulation and the enabling technologies to either monitor or enhance encapsulated cell function; Section IV gives specific examples of the methods used to encapsulate various cell types; and Section V provides an overview of the different clinical situations in which cell microencapsulation has been applied. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Thorough and practical, Cell Microencapsulation: Methods and Protocols is a valuable reference for researchers, engineers, clinicians, and other healthcare professionals, as well as food technologists who will find detailed descriptions of methods for the microencapsulation of specific cell types and their current of potential clinical and industrial applications. This volume also includes detailed information about the design and manufacture of different devices including large-scale production devices for use in cell microencapsulation.

Advanced Healthcare Materials

Advanced Healthcare Materials PDF Author: Ashutosh Tiwari
Publisher: John Wiley & Sons
ISBN: 1118773683
Category : Technology & Engineering
Languages : en
Pages : 421

Book Description
Offers a comprehensive and interdisciplinary view of cutting-edge research on advanced materials for healthcare technology and applications Advanced healthcare materials are attracting strong interest in fundamental as well as applied medical science and technology. This book summarizes the current state of knowledge in the field of advanced materials for functional therapeutics, point-of-care diagnostics, translational materials, and up-and-coming bioengineering devices. Advanced Healthcare Materials highlights the key features that enable the design of stimuli-responsive smart nanoparticles, novel biomaterials, and nano/micro devices for either diagnosis or therapy, or both, called theranostics. It also presents the latest advancements in healthcare materials and medical technology. The senior researchers from global knowledge centers have written topics including: State-of-the-art of biomaterials for human health Micro- and nanoparticles and their application in biosensors The role of immunoassays Stimuli-responsive smart nanoparticles Diagnosis and treatment of cancer Advanced materials for biomedical application and drug delivery Nanoparticles for diagnosis and/or treatment of Alzheimers disease Hierarchical modelling of elastic behavior of human dental tissue Biodegradable porous hydrogels Hydrogels in tissue engineering, drug delivery, and wound care Modified natural zeolites Supramolecular hydrogels based on cyclodextrin poly(pseudo)rotaxane Polyhydroxyalkanoate-based biomaterials Biomimetic molecularly imprinted polymers

Bone Tissue Engineering

Bone Tissue Engineering PDF Author: Jeffrey O. Hollinger
Publisher: CRC Press
ISBN: 1135501912
Category : Medical
Languages : en
Pages : 500

Book Description
Focusing on bone biology, Bone Tissue Engineering integrates basic sciences with tissue engineering. It includes contributions from world-renowned researchers and clinicians who discuss key topics such as different models and approaches to bone tissue engineering, as well as exciting clinical applications for patients. Divided into four sections, t

Cardiac Regeneration

Cardiac Regeneration PDF Author: Masaki Ieda
Publisher: Springer
ISBN: 3319561065
Category : Medical
Languages : en
Pages : 274

Book Description
This Volume of the series Cardiac and Vascular Biology offers a comprehensive and exciting, state-of-the-art work on the current options and potentials of cardiac regeneration and repair. Several techniques and approaches have been developed for heart failure repair: direct injection of cells, programming of scar tissue into functional myocardium, and tissue-engineered heart muscle support. The book introduces the rationale for these different approaches in cell-based heart regeneration and discusses the most important considerations for clinical translation. Expert authors discuss when, why, and how heart muscle can be salvaged. The book represents a valuable resource for stem cell researchers, cardiologists, bioengineers, and biomedical scientists studying cardiac function and regeneration.

Mesenchymal Stem Cell Derived Exosomes

Mesenchymal Stem Cell Derived Exosomes PDF Author: Yaoliang Tang
Publisher: Academic Press
ISBN: 0128004975
Category : Science
Languages : en
Pages : 287

Book Description
Mesenchymal stem cell-derived exosomes are at the forefront of research in two of the most high profile and funded scientific areas – cardiovascular research and stem cells. Mesenchymal Stem Cell Derived Exosomes provides insight into the biofunction and molecular mechanisms, practical tools for research, and a look toward the clinical applications of this exciting phenomenon which is emerging as an effective diagnostic. Primarily focused on the cardiovascular applications where there have been the greatest advancements toward the clinic, this is the first compendium for clinical and biomedical researchers who are interested in integrating MSC-derived exosomes as a diagnostic and therapeutic tool. - Introduces the MSC-exosome mediated cell-cell communication - Covers the major functional benefits in current MSC-derived exosome studies - Discusses strategies for the use of MSC-derived exosomes in cardiovascular therapies

Therapeutic Oligonucleotides

Therapeutic Oligonucleotides PDF Author: Jens Kurreck
Publisher: Royal Society of Chemistry
ISBN: 0854041168
Category : Medical
Languages : en
Pages : 362

Book Description
This book provides a compelling overall update on current status of RNA interference

Mucosal Vaccines

Mucosal Vaccines PDF Author: Hiroshi Kiyono
Publisher: Elsevier
ISBN: 0080537057
Category : Medical
Languages : en
Pages : 501

Book Description
This comprehensive, authoritative treatise covers all aspects of mucosal vaccines including their development, mechanisms of action, molecular/cellular aspects, and practical applications. The contributing authors and editors of this one-of-a-kind book are very well known in their respective fields. Mucosal Vaccines is organized in a unique format in which basic, clinical, and practical aspects of the mucosal immune system for vaccine development are described and discussed. This project is endorsed by the Society for Mucosal Immunology. - Provides the latest views on mucosal vaccines - Applies basic principles to the development of new vaccines - Links basic, clinical, and practical aspects of mucosal vaccines to different infectious diseases - Unique and user-friendly organization