Beta 1 Integrins in Bone Formation During Development and Engineering Integrin-specific Hydrogels for Enhanced Bone Healing PDF Download
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Author: Asha Shekaran
Publisher:
ISBN:
Category : Biocolloids
Languages : en
Pages :
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Book Description
Healing large bone defects remains a clinical challenge. While autografts are the gold standard treatment for large bone defects, they are limited by availability and donor site pain. Growth factor treatments such as BMP therapy provide a promising alternative but are expensive and present clinical safety concerns, primarily due to delivery of BMPs at supraphysiological doses. Integrins are ECM receptors which mediate crucial cell functions such as adhesion and differentiation. Therefore, understanding the role of integrins in bone formation and directing desired interactions may enable modulation of host cell functions for therapeutic applications. In this work, beta 1 integrins were deleted in osteolineage cells of transgenic mice at three different stages of differentiation to elucidate their role in bone development. We also engineered bioartificial PEG-based matrices which target the pro-osteogenic alpha 2 beta 1 integrin to promote bone healing. Conditional deletion of beta 1 integrins in osteochondroprogenitor cells under the Twist 2 promoter resulted in severe pre-natal skeletal mineralization defects and embryonic lethality. Targeted deletion of beta 1 integrins in osterix-expressing osteoprogenitors resulted in growth abnormalities, reduced calvarial mineralization, impaired femur development, and tooth defects. However, mice lacking beta 1 integrins in osteocalcin-expressing osteoblasts and osteocytes displayed only a mild skeletal phenotype, indicating that beta 1 integrins play an important role in early skeletal development, but are not required for mature osteoblast function. PEG hydrogels functionalized with the integrin-specific GFOGER ligand enhanced bone regeneration, induced defect bridging in combination with low doses of rhBMP-2 and stimulated improved bone healing compared collagen sponges, which are the clinical standard delivery vector for BMP-2 therapy. These results suggest that treatment with bioartificial integrin-specific PEG hydrogels may be a promising clinical strategy for bone regeneration in large bone defects.
Author: Asha Shekaran
Publisher:
ISBN:
Category : Biocolloids
Languages : en
Pages :
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Book Description
Healing large bone defects remains a clinical challenge. While autografts are the gold standard treatment for large bone defects, they are limited by availability and donor site pain. Growth factor treatments such as BMP therapy provide a promising alternative but are expensive and present clinical safety concerns, primarily due to delivery of BMPs at supraphysiological doses. Integrins are ECM receptors which mediate crucial cell functions such as adhesion and differentiation. Therefore, understanding the role of integrins in bone formation and directing desired interactions may enable modulation of host cell functions for therapeutic applications. In this work, beta 1 integrins were deleted in osteolineage cells of transgenic mice at three different stages of differentiation to elucidate their role in bone development. We also engineered bioartificial PEG-based matrices which target the pro-osteogenic alpha 2 beta 1 integrin to promote bone healing. Conditional deletion of beta 1 integrins in osteochondroprogenitor cells under the Twist 2 promoter resulted in severe pre-natal skeletal mineralization defects and embryonic lethality. Targeted deletion of beta 1 integrins in osterix-expressing osteoprogenitors resulted in growth abnormalities, reduced calvarial mineralization, impaired femur development, and tooth defects. However, mice lacking beta 1 integrins in osteocalcin-expressing osteoblasts and osteocytes displayed only a mild skeletal phenotype, indicating that beta 1 integrins play an important role in early skeletal development, but are not required for mature osteoblast function. PEG hydrogels functionalized with the integrin-specific GFOGER ligand enhanced bone regeneration, induced defect bridging in combination with low doses of rhBMP-2 and stimulated improved bone healing compared collagen sponges, which are the clinical standard delivery vector for BMP-2 therapy. These results suggest that treatment with bioartificial integrin-specific PEG hydrogels may be a promising clinical strategy for bone regeneration in large bone defects.
Author: Catherine Diane Reyes
Publisher:
ISBN:
Category : Biomedical materials
Languages : en
Pages :
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Book Description
Cell adhesion to the extracellular matrix through cell-surface integrin receptors is essential to development, wound healing, and tissue remodeling and therefore represents a central theme in the design of bioactive surfaces that successfully interface with the body. This is especially significant in the areas of integrative implant coatings since adhesion triggers signals that regulate cell cycle progression and differentiation in multiple cellular systems. The interactions of osteoblasts with their surrounding extracellular matrix are essential for skeletal development and homeostasis and the maintenance of the mature osteoblastic phenotype. Our objective was to engineer integrin-specific bioactive surfaces that support osteoblastic differentiation and promote osseointegration by mimicking these interactions. We target two specific integrins essential to osteoblast differentiation the type I collagen receptor alpha2beta1 and the fibronectin receptor alpha5beta1. The central hypothesis of this project was that the controlled presentation of type I collagen and fibronectin binding domains onto well-defined substrates would result in integrin-specific bioadhesive surfaces that support osteoblastic differentiation, matrix mineralization, and osseointegration. We have demonstrated that these biomimetic peptides enhance bone formation and mechanical osseointegration on titanium implants in a rat tibia cortical bone model. We have also shown that the presentation of multiple integrin-binding ligands synergize to enhance intracellular signaling and proliferation. Finally, we demonstrate the advantage of the short biomimetic peptides over the native ECM proteins. This research is significant because it addresses current orthopaedic implant limitations by specifically targeting cellular responses that are critical to osteoblastic differentiation and bone formation. This biomolecular approach provides a versatile and robust strategy for developing bioactive surfaces that enhance bone repair and osseointegration of orthopaedic implants.
Author: Meredith A. Myers
Publisher:
ISBN:
Category : Cell adhesion
Languages : en
Pages :
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Book Description
Osseointegration, or the direct integration of an implant into bone tissue, is necessary for implant success. Titanium is commonly used clinically in dental and orthopaedic implants because of its passivating oxide layer, which facilitates osseointegration, and its mechanical properties such as a modulus of elasticity similar to bone. Diverse studies have shown that surface microtopography, chemistry, and surface energy affect osteoblast behavior. The problem with these studies is that they access the average behavior of a culture in response to a substrate and not the behavior of individual cells. The objective of this study was to develop a method for correlating the behavior of individual cells with the characteristics of the surface underneath them. More specifically, this work developed a method to correlate integrin beta-1 (©3¡2©60́9©30́Œ©2℗ư©3¡2â2́Ơš©30́(©2℗ø1) expression with the surface characteristics under individual cells. Integrins are cell surface receptors that bind to specific proteins in the extracellular matrix adsorbed on the implant surface. Previous work has shown that expression of certain integrins is increased when osteoblasts on titanium substrates develop a more differentiated phenotype, and that integrin ©3¡2©60́9©30́Œ©2℗ư©3¡2â2́Ơš©30́(©2℗ø1 is necessary for osteoblast response to roughness on titanium substrates. This study used molecular beacons specific to integrin ©3¡2©60́9©30́Œ©2℗ư©3¡2â2́Ơš©30́(©2℗ø1 to quantify integrin ©3¡2©60́9©30́Œ©2℗ư©3¡2â2́Ơš©30́(©2℗ø1 expression of MG63 cells cultured on titanium disks. A template was designed to coordinate the location of cells using fluorescence microscopy and scanning electron microscopy (SEM) in reference to laser etchings on the disks. After live cell imaging, cells were fixed, dried, and critical point dried for focused ion beam (FIB) milling. Transmission electron microscopy (TEM) sections of cells identified with high and low integrin ©3¡2©60́9©30́Œ©2℗ư©3¡2â2́Ơš©30́(©2℗ø1 molecular beacon intensity were milled, and cells with high and low integrin ©3¡2©60́9©30́Œ©2℗ư©3¡2â2́Ơš©30́(©2℗ø1 molecular beacon intensity were also serial sectioned. While our TEM results were inconclusive, SEM images from serial sectioning showed contact points between the cell body and the substrate, consistent with previous results. Cells cultured on pretreatment (PT) or sandblasted acid etched (SLA) titanium surfaces were also serial sectioned, showing that cells on SLA surfaces have more regions of contact between the cells and the substrate than cells on PT surfaces. This work is significant as it is the first study to develop a method to correlate individual cell behavior with the substrate surface characteristics under the individual cells. Previous studies have reported the average cell behavior in response to their substrates, while this work allows for the study of substrate surface characteristics that positively affect integrin ©3¡2©60́9©30́Œ©2℗ư©3¡2â2́Ơš©30́(©2℗ø1 expression in individual cells. Further optimization of the fluorescence imaging process and FIB milling process could be done, and the method developed in this study could be used in future studies to investigate surface characteristics after using other fluorescent analyses of cell behavior, such as immunocytochemistry.
Author: Jeffrey O. Hollinger
Publisher: CRC Press
ISBN: 1135501912
Category : Medical
Languages : en
Pages : 500
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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
Author: Gregory H. Hudalla
Publisher: Royal Society of Chemistry
ISBN: 1849738335
Category : Medical
Languages : en
Pages : 422
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Book Description
Mimicking the Extracellular Matrix approaches this topic from both basic science and practical engineering perspectives. Suitable for undergraduates, postgraduates, and academics, this text aims to unify the current knowledge of ECM biology and matrix-mimicking biomaterials.
Author: William R Wagner
Publisher: Academic Press
ISBN: 0128161388
Category : Technology & Engineering
Languages : en
Pages : 1612
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Book Description
The revised edition of the renowned and bestselling title is the most comprehensive single text on all aspects of biomaterials science from principles to applications. Biomaterials Science, fourth edition, provides a balanced, insightful approach to both the learning of the science and technology of biomaterials and acts as the key reference for practitioners who are involved in the applications of materials in medicine.This new edition incorporates key updates to reflect the latest relevant research in the field, particularly in the applications section, which includes the latest in topics such as nanotechnology, robotic implantation, and biomaterials utilized in cancer research detection and therapy. Other additions include regenerative engineering, 3D printing, personalized medicine and organs on a chip. Translation from the lab to commercial products is emphasized with new content dedicated to medical device development, global issues related to translation, and issues of quality assurance and reimbursement. In response to customer feedback, the new edition also features consolidation of redundant material to ensure clarity and focus. Biomaterials Science, 4th edition is an important update to the best-selling text, vital to the biomaterials’ community. The most comprehensive coverage of principles and applications of all classes of biomaterials Edited and contributed by the best-known figures in the biomaterials field today; fully endorsed and supported by the Society for Biomaterials Fully revised and updated to address issues of translation, nanotechnology, additive manufacturing, organs on chip, precision medicine and much more. Online chapter exercises available for most chapters
Author: Mario Barbosa
Publisher: Woodhead Publishing
ISBN: 008100852X
Category : Technology & Engineering
Languages : en
Pages : 392
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Book Description
Peptides and Proteins as Biomaterials for Tissue Regeneration and Repair highlights the various important considerations that go into biomaterial development, both in terms of fundamentals and applications. After covering a general introduction to protein and cell interactions with biomaterials, the book discusses proteins in biomaterials that mimic the extracellular matrix (ECM). The properties, fabrication and application of peptide biomaterials and protein-based biomaterials are discussed in addition to in vivo and in vitro studies. This book is a valuable resource for researchers, scientists and advanced students interested in biomaterials science, chemistry, molecular biology and nanotechnology. Presents an all-inclusive and authoritative coverage of the important role which protein and peptides play as biomaterials for tissue regeneration Explores protein and peptides from the fundamentals, to processing and applications Written by an international group of leading biomaterials researchers
Author: Alessandro Rozim Zorzi
Publisher: BoD – Books on Demand
ISBN: 9535125389
Category : Medical
Languages : en
Pages : 388
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Book Description
Advanced Techniques in Bone Regeneration is a book that brings together over 15 chapters, written by leading practitioners and researchers, of the latest advances in the area, including surgical techniques, new discoveries, and promising methods involving biomaterials and tissue engineering. This book is intended for all who work in the treatment of disorders involving problems with the regeneration of bone tissue, are doctors or dentists, as well as are researchers and teachers involved in this exciting field of scientific knowledge.
Author: Tiago G. Fernandes
Publisher: Academic Press
ISBN: 0128166703
Category : Science
Languages : en
Pages : 284
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Book Description
Engineering Strategies for Regenerative Medicine considers how engineering strategies can be applied to accelerate advances in regenerative medicine. The book provides relevant and up-to-date content on key topics, including the interdisciplinary integration of different aspects of stem cell biology and technology, diverse technologies, and their applications. By providing massive amounts of data on each individual, recent scientific advances are rapidly accelerating medicine. Cellular, molecular and genetic parameters from biological samples combined with clinical information can now provide valuable data to scientists, clinicians and ultimately patients, leading to the development of precision medicine. Equally noteworthy are the contributions of stem cell biology, bioengineering and tissue engineering that unravel the mechanisms of disease, regeneration and development. Considers how engineering strategies can accelerate novel advances in regenerative medicine Takes an interdisciplinary approach, integrating different aspects of research, technology and application Provides up-to-date coverage on this rapidly developing area of medicine Presents insights from an experienced and cross-disciplinary group of researchers and practitioners with close links to industry
Author: Francesco Cellesi
Publisher: Frontiers Media SA
ISBN: 2889660222
Category : Science
Languages : en
Pages : 180
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Book Description
This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.
