Regulated turnover of extracellular matrix (ECM) is an important component of tissue homeostasis. In recent years, the enzymes that participate in, and control ECM turnover have been the focus of research that touches on development, tissue remodeling, inflammation and disease. This volume in the Biology of Extracellular Matrix series provides a review of the known classes of proteases that degrade ECM both outside and inside the cell. The specific EMC proteases that are discussed include cathepsins, bacterial collagenases, matrix metalloproteinases, meprins, serine proteases, and elastases. The volume also discusses the domains responsible for specific biochemical characteristics of the proteases and the physical interactions that occur when the protease interacts with substrate. The topics covered in this volume provide an important context for understanding the role that matrix-degrading proteases play in normal tissue remodeling and in diseases such as cancer and lung disease.

The Second Edition of Connective Tissue and Its Heritable Disorders: Molecular, Genetic, and Medical Aspects is the definitive reference text in its field, with over 40% more pages on the nature, diagnosis, and treatment of disease than its predecessor. Collecting new research on disorders detailed in the first edition as well as on those previously excluded, editors Peter Royce and Beat Steinmann provide the most up-to-date clinical and scientific information for medical specialists treating affected individuals. Features of this revised and updated volume include detailed reviews of the clinical diagnosis, mode of inheritance, risk of recurrence, and prenatal diagnosis of each inherited connective tissue disorder; a thorough description of the morphology of connective tissues; a completely updated and revised section on the biology of the extracellular matrix; and the addition of syndromes such as craniosyntosis, and disorders of sulfate metabolism.

Regulated turnover of extracellular matrix (ECM) is an important component of tissue homeostasis. In recent years, the enzymes that participate in, and control ECM turnover have been the focus of research that touches on development, tissue remodeling, inflammation and disease. This volume in the Biology of Extracellular Matrix series provides a review of the known classes of proteases that degrade ECM both outside and inside the cell. The specific EMC proteases that are discussed include cathepsins, bacterial collagenases, matrix metalloproteinases, meprins, serine proteases, and elastases. The volume also discusses the domains responsible for specific biochemical characteristics of the proteases and the physical interactions that occur when the protease interacts with substrate. The topics covered in this volume provide an important context for understanding the role that matrix-degrading proteases play in normal tissue remodeling and in diseases such as cancer and lung disease.

In the ten-year interval since the first edition of this volume went to press, our knowledge of extracellular matrix (ECM) function and structure has enor mously increased. Extracellular matrix and cell-matrix interaction are now routine topics in the meetings and annual reviews sponsored by cell biology societies. Research in molecular biology has so advanced the number of known matrix molecules and the topic of gene structure and regulation that we won dered how best to incorporate the new material. For example, we deliberated over the inclusion of chapters on molecular genetics. We decided that with judicious editing we could present the recent findings in molecular biology within the same cell biology framework that was used for the first edition, using three broad headings: what is extracellular matrix, how is it made, and what does it do for cells? Maintaining control over the review of literature on the subject of ECM was not always an easy task, but we felt it was essential to production of a highly readable volume, one compact enough to serve the the student as an introduction and the investigator as a quick update on graduate the important recent discoveries. The first edition of this volume enjoyed con hope the reader finds this edition equally useful. siderable success; we D. Hay Elizabeth vii Contents Introductory Remarks 1 Elizabeth D. Hay PART I. WHAT IS EXTRACELLULAR MATRIX? Chapter 1 Collagen T. F. Linsenmayer 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2. The Collagen Molecule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2. 1. Triple-Helical Domain(s) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Knowledge of the extracellular matrix (ECM) is essential to understand cellular differentiation, tissue development, and tissue remodeling. This volume of the series “Biology of Extracellular Matrix” provides a timely overview of the structure, regulation, and function of the major macromolecules that make up the extracellular matrix. It covers topics such as collagen types and assembly of collagen-containing suprastructures, basement membrane, fibronectin and other cell-adhesive glycoproteins, proteoglycans, microfibrils, elastin, fibulins and matricellular proteins, such as thrombospondin. It also explores the concept that ECM components together with their cell surface receptors can be viewed as intricate nano-devices that allow cells to physically organize their 3-D-environment. Further, the role of the ECM in human disease and pathogenesis is discussed as well as the use of model organisms in elucidating ECM function.

The extracellular matrix (ECM) is where cells live. It is composed of collagen and elastic fibers, glycosaminoglycans and proteoglycans, and several glycoproteins. In most tissues, fibril-forming collagen type I is the major constituent of ECM.The function of the ECM goes beyond providing mechanical support to cells and tissues. As cells are embedded into the ECM and interact with its components through their surface receptors, cell–ECM interaction plays a key role in influencing different cell activities, such as cell proliferation and migration. The ECM also sequesters and releases growth factors affecting important cellular pathways. Overall, the ECM strongly influences and affects cell behavior and tissue homeostasis. ECM is a highly dynamic structural network that continuously undergoes controlled remodeling mediated by matrix-degrading enzymes, the matrix metalloproteinases (MMPs), under normal conditions. Quantitative and qualitative deregulation of ECM remodeling and, especially, of collagen turnover, is responsible for the alteration of ECM composition and structure, associated with the development and progression of several pathological conditions, such as organ fibrosis (determined by the abnormal accumulation of ECM components) and tumor invasion. The understanding of the diverse biological roles and properties of the ECM components is pivotal to the development of new therapeutic tools for disease treatment.

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

Looking at the area of the extracellular matrix of connective tissue, including the results and concepts which have recently been generated, this text describes the structural characteristics of extracellular molecules and discusses the interaction between the cell and the extracellular matrix.