Integrin-specific Surfaces to Promote Bone Formation and Osseointegration PDF Download
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Author: Andres Garcia
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Author: Andres Garcia
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Author: Catherine Diane Reyes
Publisher:
ISBN:
Category : Biomedical materials
Languages : en
Pages :
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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: Asha Shekaran
Publisher:
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Category : Biocolloids
Languages : en
Pages :
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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: Ethan Major Lotz
Publisher:
ISBN:
Category :
Languages : en
Pages : 208
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In cases of compromised bone remodeling like osteoporosis, insufficient osseointegration occurs and results in implant failure. Implant retention relies on proper secondary fixation, which is developed during bone remodeling. This process is disrupted in metastatic bone diseases like osteoporosis. Osteoporosis is characterized low bone mass and bone strength resulting from either accelerated osteoclast-mediated bone resorption or impaired osteoblast-mediated bone formation. These two processes are not independent phenomena. In fact, osteoporosis can be viewed as a breakdown of the cellular communication connecting bone resorption to bone formation. Because bone remodeling occurs at temporally generated specific anatomical sites and at different times, local regulators that control cross-talk among the cells of the BRU are important. Previous studies show Ti implant surface characteristics like roughness, hydrophilicity, and chemistry influence the osteoblastic differentiation of human M.S. Cs and maturation of OBs. Furthermore, microstructured Ti surfaces modulate the production of factors shown to be important in the reciprocal communication necessary for the maintenance of healthy bone remodeling. Semaphorin signaling proteins are known to couple the communication of osteoblasts to osteoclasts and are capable of stimulating bone formation or bone resorption depending on certain cues. Implant surface properties can be optimized to exploit these effects to favor rapid osseointegration in patients with osteoporosis.
Author: Jeffrey O. Hollinger
Publisher: CRC Press
ISBN: 1135501912
Category : Medical
Languages : en
Pages : 500
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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: Meredith A. Myers
Publisher:
ISBN:
Category : Cell adhesion
Languages : en
Pages :
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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: 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: Kevin Healy
Publisher: Elsevier
ISBN: 0081006926
Category : Technology & Engineering
Languages : en
Pages : 4865
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Book Description
Comprehensive Biomaterials II, Second Edition, Seven Volume Set brings together the myriad facets of biomaterials into one expertly-written series of edited volumes. Articles address the current status of nearly all biomaterials in the field, their strengths and weaknesses, their future prospects, appropriate analytical methods and testing, device applications and performance, emerging candidate materials as competitors and disruptive technologies, research and development, regulatory management, commercial aspects, and applications, including medical applications. Detailed coverage is given to both new and emerging areas and the latest research in more traditional areas of the field. Particular attention is given to those areas in which major recent developments have taken place. This new edition, with 75% new or updated articles, will provide biomedical scientists in industry, government, academia, and research organizations with an accurate perspective on the field in a manner that is both accessible and thorough. Reviews the current status of nearly all biomaterials in the field by analyzing their strengths and weaknesses, performance, and future prospects Covers all significant emerging technologies in areas such as 3D printing of tissues, organs and scaffolds, cell encapsulation; multimodal delivery, cancer/vaccine - biomaterial applications, neural interface understanding, materials used for in situ imaging, and infection prevention and treatment Effectively describes the many modern aspects of biomaterials from basic science, to clinical applications
Author: Mitsuhiro Ebara
Publisher: Springer
ISBN: 4431544003
Category : Technology & Engineering
Languages : en
Pages : 380
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Book Description
This book provides comprehensive coverage of smart biomaterials and their potential applications, a field that is developing at a very rapid pace. Because smart biomaterials are an emerging class of biomaterials that respond to small changes in external stimuli with large discontinuous changes in their physical properties, they have been designed to act as an “on–off” switch for, among others, bio separation, immunoanalysis, drug delivery technologies, gene therapy, diagnostics, bio sensors and artificial muscles. After an introduction to the topic and the history of smart biomaterials, the author gives the reader an in-depth look at the properties, mechanics, and characterization of smart biomaterials including hydrogels, particles, assemblies, surfaces, fibers and conjugates. Information on the wide range of applications for these materials follows, including drug delivery, tissue engineering, diagnostics, biosensors, bio separation and actuators. In addition, recent advances in shape memory biomaterials as active components of medical devices are also presented.
Author: Yuangang Liu
Publisher: Frontiers Media SA
ISBN: 2832515061
Category : Science
Languages : en
Pages : 257
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