The Characterization of Hyaluronic Acid and Polyethylene Glycol Hydrogels for Neural Tissue Engineering PDF Download
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Author: Emily Rose Aurand
Publisher:
ISBN:
Category :
Languages : en
Pages : 172
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Book Description
Neural tissue engineering through the use of biomaterials holds great promise for treating a wide variety of neurological disorders. The customizable nature of hydrogels provides the opportunity to mimic the brain's unique extracellular matrix (ECM). Hydrogels can be used to recreate this ECM environment to support neural cells in vitro, through 3D culturing, or during transplantation procedures. To be effective, hydrogels must be characterized chemically, physically, and mechanically, and the biocompatibility of these materials with neural cells and brain tissue must be defined. Twenty-five hydrogels were created from ratios of hyaluronic acid (HA) and poly(ethylene glycol) (PEG). Hydrogels were assessed for the properties of polymerization, degradation, and compressive modulus, and the cytocompatibility with encapsulated neural progenitor cells (NPC) from fetal and adult sources. The physical and mechanical properties of the hydrogels were found to be dependent on the polymer concentration. Additionally, the compressive moduli of the hydrogels were comparable to rodent brain tissue, indicating that the hydrogel formulations developed were physiologically relevant. Subsequently, NPC derived from fetal and adult rats (fNPC and aNPC, respectively) were encapsulated within the hydrogels. Twenty-four hour cell survival was highest at lower concentrations of HA and PEG. Three-week fNPC and aNPC differentiation was demonstrated to be influenced by mechanical properties. Fetal-NPC generally produced greater numbers of astrocytes in stiffer hydrogels, while increased numbers of neurons were observed in softer hydrogels. Greater numbers of aNPC became neuronal, regardless of stiffness. When two chosen hydrogels were used to implant NPC into the brain, the results suggested that encapsulated NPC survived at up to 50% two months post-implantation, indicating good cytocompatibility. Further, the implanted cells were able to migrate from the hydrogel into the surrounding brain tissue farther than unencapsulated cells. Immunolabeling for glial cells demonstrated that the hydrogels elicited a similar immune response as control treatments, establishing the histocompatibility with brain tissue. Based on these studies, HA-PEG hydrogels were biocompatible and could be used therapeutically in the brain. Further modifications and specializations of these hydrogels, such as the inclusion of growth factors or attachment factors, may provide specific therapeutic support for encapsulated cells and/or neurodegenerative disorders.
Author: Emily Rose Aurand
Publisher:
ISBN:
Category :
Languages : en
Pages : 172
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Book Description
Neural tissue engineering through the use of biomaterials holds great promise for treating a wide variety of neurological disorders. The customizable nature of hydrogels provides the opportunity to mimic the brain's unique extracellular matrix (ECM). Hydrogels can be used to recreate this ECM environment to support neural cells in vitro, through 3D culturing, or during transplantation procedures. To be effective, hydrogels must be characterized chemically, physically, and mechanically, and the biocompatibility of these materials with neural cells and brain tissue must be defined. Twenty-five hydrogels were created from ratios of hyaluronic acid (HA) and poly(ethylene glycol) (PEG). Hydrogels were assessed for the properties of polymerization, degradation, and compressive modulus, and the cytocompatibility with encapsulated neural progenitor cells (NPC) from fetal and adult sources. The physical and mechanical properties of the hydrogels were found to be dependent on the polymer concentration. Additionally, the compressive moduli of the hydrogels were comparable to rodent brain tissue, indicating that the hydrogel formulations developed were physiologically relevant. Subsequently, NPC derived from fetal and adult rats (fNPC and aNPC, respectively) were encapsulated within the hydrogels. Twenty-four hour cell survival was highest at lower concentrations of HA and PEG. Three-week fNPC and aNPC differentiation was demonstrated to be influenced by mechanical properties. Fetal-NPC generally produced greater numbers of astrocytes in stiffer hydrogels, while increased numbers of neurons were observed in softer hydrogels. Greater numbers of aNPC became neuronal, regardless of stiffness. When two chosen hydrogels were used to implant NPC into the brain, the results suggested that encapsulated NPC survived at up to 50% two months post-implantation, indicating good cytocompatibility. Further, the implanted cells were able to migrate from the hydrogel into the surrounding brain tissue farther than unencapsulated cells. Immunolabeling for glial cells demonstrated that the hydrogels elicited a similar immune response as control treatments, establishing the histocompatibility with brain tissue. Based on these studies, HA-PEG hydrogels were biocompatible and could be used therapeutically in the brain. Further modifications and specializations of these hydrogels, such as the inclusion of growth factors or attachment factors, may provide specific therapeutic support for encapsulated cells and/or neurodegenerative disorders.
Author: Maurice N Collins
Publisher: Smithers Rapra
ISBN: 1909030783
Category : Medical
Languages : en
Pages : 238
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Book Description
Hyaluronic acid (HA) is found in extracellular tissue in many parts of the body. It is a material of increasing importance to biomaterials science and is finding applications in diverse areas ranging from tissue culture scaffolds to cosmetic materials. Its properties, both physical and biochemical, in solution or hydrogel form, are extremely attractive for various technologies concerned with body repair. This book considers the materials science behind some of the important biomedical and therapeutic applications that are emerging for HA. Key characteristics such as its mechanical properties, biological function and degradation are discussed. The latest technologies in chemical modification and crosslinking strategies are analysed and emerging applications in soft and hard tissue repair are highlighted. The first objective of the book, which consists of a collection of chapters from leading researchers across the globe, is to highlight the role of HA based hydrogels as scaffolds in sustaining stem cells for transplantation and regrowth. The second objective is to detail the significant influence of HA derived materials in the latest advances in cancer therapy, general therapeutics and cosmetics. The third objective is to link the structure-property relationships of HA to medical function and application while reflecting on current clinical and market trends. The book will be of interest to those involved in HA research for medical device and therapeutic applications. Graduate and undergraduate students engaged in the fields of biomedical engineering, materials science, chemistry, medical science, pharmaceutical science and polymer science will find this book of particular interest.
Author: Shahid Ali Khan
Publisher: Walter de Gruyter GmbH & Co KG
ISBN: 3111334228
Category : Technology & Engineering
Languages : en
Pages : 185
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Book Description
With the advancement in medicinal chemistry and material science, several highly specific, biocompatible and non-toxic therapeutic agents have been discovered and successfully applied for various clinical applications. Many of the conventional constraints of clinical therapies have been replaced and overcome by the multifaceted applications of material science and nanotechnology. Recently, material science-based therapeutic agents are the major global pharmaceutical market and are believed to mount exponentially shortly. Among the various therapeutic agents, hydrogels are one of the most widely applied materials used in the treatment of various diseases, and one of the most diverse materials that are used for multipurpose applications. Hydrogels were the first biomaterials used for Human being. Hydrogels are polymeric linkages, water-insoluble, however, sometimes established as a colloidal gel in water. Hydrogels are the superabsorbent materials because it can absorb more than 90% water, and hence regarded as natural living tissue. Mechanically strong hydrogels were synthesized by the advent of new synthetic strategies. Owing to the swollen properties, three-dimensional polymer network, and strong mechanical characteristics, these are widely used in catalysis, adsorption, drug delivery systems for proteins, contact lenses, wound dressings, wound healing, bone regeneration, tissue engineering, baby diapers, food rheology, and many others. Due to their diverse applications, hydrogels are considered one of the smartest materials in pharmaceutics, and are eco-friendly materials, cheap, and have good recyclability. They are used as therapeutic agents in different health sectors. As they are very sensitive to target, therefore it is considered favorite and preferred choice in biomedical sectors. Patients are psychologically scared of surgeries regarding huge expenses and failure. So researchers are working on hydrogels as alternative surgical replacement. In most cases, they have successfully achieved research on hydrogels in bones and tissues repairment. It might be hope of life for serious patients in future. The domain of this work will cover state of the art potentials and applications in various technological areas.
Author: Thakur Raghu Raj Singh
Publisher: CRC Press
ISBN: 1498748627
Category : Medical
Languages : en
Pages : 353
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Book Description
Hydrogels are crosslinked, macromolecular polymeric materials arranged in a three-dimensional network, which can absorb and retain large amounts of water. Hydrogels are commonly used in clinical practice and experimental medicine for a wide range of applications, including drug delivery, tissue engineering and regenerative medicine, diagnostics, cellular immobilization, separation of biomolecules or cells, and barrier materials to regulate biological adhesions. This book elucidates the underlying concepts and emerging applications of hydrogels and will provide key case studies and critical analysis of the existing research.
Author:
Publisher: ScholarlyEditions
ISBN: 1481691546
Category : Science
Languages : en
Pages : 529
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Book Description
Polyethylene Glycols—Advances in Research and Application: 2013 Edition is a ScholarlyEditions™ book that delivers timely, authoritative, and comprehensive information about Hydrogel. The editors have built Polyethylene Glycols—Advances in Research and Application: 2013 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Hydrogel in this book to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Polyethylene Glycols—Advances in Research and Application: 2013 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.
Author: Kevin Worrell
Publisher:
ISBN:
Category : Colloids
Languages : en
Pages :
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Book Description
Biodegradable hydrogels have become very promising materials for a number of biomedical applications, including tissue engineering and drug delivery. For optimal tissue engineering design, the mechanical properties of hydrogels should match those of native tissues as closely as possible because these properties are known to affect the behavior and function of cells seeded in the hydrogels. At the same time, high water-contents, large mesh sizes and well-tuned degradation rates are favorable for the controlled release of growth factors and for adequate transport of nutrients through the hydrogel during tissue regeneration. With these factors in mind, the goal of this research was to develop and investigate the behavior of injectable, biodegradable hydrogels with enhanced stiffness properties that persist even at high degrees of swelling. In order to do this, degradable functionalities were incorporated into photo-crosslinkable poly(ethylene glycol) and poly(acrylic acid) hydrogels, and these two components were used to make a series of double-network hydrogels. Synthesis of the precursor macromers, photopolymerization of the hydrogels, and structural parameters of the hydrogels were analyzed. The composition and the molecular weight between crosslinks (Mc) of the hydrogel components were varied, and the degradation, swelling, thermal and mechanical properties of the hydrogels were characterized over various time scales. These properties were compared to corresponding properties of the component single-network hydrogels.
Author: Anushree Datta
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Author: Talar Tokatlian
Publisher:
ISBN:
Category :
Languages : en
Pages : 141
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Book Description
Natural wound healing and angiogenesis are a result of a cascade of bioactive signals being delivered at specified times in response to local biological cues. However, for ischemic wounds which cannot heal naturally, external therapies are required. We are interested in engineering hydrogel scaffolds for cell-demanded release of non-viral DNA nanoparticles to more efficiently guide blood vessel formation in such tissues. Vascularization within tissue-engineered constructs still remains the primary cause of construct failure following implantation. While a myriad of approaches to enhance the vascularization of implants are being investigated none have completely solved the problem. We investigated two hypotheses to enhance scaffold vascularization, both long-term mechanical support and DNA delivery. Our preliminary in vivo studies showed that after subcutaneous implantation for three weeks enzymatically degradable hydrogels had cellular infiltration only at the periphery of the hydrogel, while hydrogels with micron sized interconnected pores (μ-pore) were extensively infiltrated. Significant positive staining for endothelial markers (PECAM) was also found for μ-pore implants and not for nano-pore implants, even in the absence of pro-angiogenic factors. We hypothesized that an open pore structure will increase the rate of vascularization through enhanced cellular infiltration and that the added delivery of DNA encoding for angiogenic growth factors would result in long lasting angiogenic signals. To test these hypotheses, two approaches to make DNA-loaded enzymatically degradable μ-pore hydrogel scaffolds were developed. In the first approach, polystyrene nanoparticles, similar in size to DNA polyplexes, were immobilized to the hydrogel pore surface through protease sensitive peptide tethers. Enzymatically degradable tethers have been utilized for the immobilization and release of growth factors and small drugs, which are only liberated by cleavage caused by cell secreted proteases, such as matrix metalloproteinases (MMPs) or plasmins, during local tissue remodeling. These proteases are known to be up-regulated during wound healing, microenvironment remodeling, and in diseased states and can, therefore, serve as triggers for bioactive signal delivery. The goal was to use peptide sequences that have been shown to degrade at different rates through the action of MMPs to achieve temporally controlled nanoparticle internalization by cells that overexpress MMPs. Cellular internalization of the peptide-immobilized nanoparticles was shown to be a function of the peptide sensitivity to proteases, the number of tethers between the nanoparticle and the biomaterial and the MMP expression profile of the seeded cells. By immobilizing nanoparticles through protease sensitive peptide tethers, release was tailored specifically for an intended cellular target, which over-expresses such proteases. Alternatively, in the second approach, μ-pore hyaluronic acid-MMP (HA-MMP) hydrogels were used to encapsulate a high concentration of DNA/poly(ethylene imine) polyplexes using a previously developed caged nanoparticle encapsulation (CnE) technique. Porous hydrogels provide the additional advantages of being able to effectively seed cells in vitro post scaffold fabrication and allow for cell spreading and proliferation without requiring extensive degradation. Thus, release of encapsulated DNA polyplexes was assessed in the presence of mMSCs in hydrogels of various pore sizes (30, 60, and 100 μm). Steady release was observed starting by day four for up to ten days for all investigated pore sizes. Likewise, transgene expression in seeded cells was sustained over this period, although significant differences between different pore sizes were not observed. Cell viability was also shown to remain high over time, even in the presence of high concentrations of DNA polyplexes. Combined these results suggested that DNA nanoparticle internalization and subsequent transgene expression could be controlled by both the protease expression profile of the seeded or infiltrating cells as well as the structural properties of the hydrogel. Using the knowledge acquired through these in vitro models, 100 and 60 μm porous and nano-pore HA-MMP hydrogels were used to study scaffold-mediated gene delivery for local gene therapy in both a subcutaneous implant and wound healing mouse models. Hydrogels with encapsulated pro-angiogenic (pVEGF) or reporter (pGFPluc) plasmids were tested for their ability to induce an enhanced angiogenic response by transfecting infiltrating cells in vivo. GFP expression in control hydrogels was used to track transfection at one, three, and six weeks in the subcutaneous implant study. While GFP-expressing transfected cells were present inside all hydrogel samples over the course of the study, transfection levels peaked around week three for 100 and 60 μm porous hydrogels. Transfection in nano-pore hydrogels continued to increase over time corresponding with continued gel degradation. Transfection levels of pVEGF, however, did not seem to be high enough to enhance angiogenesis by increasing vessel number, maturity, or size. Only in 60 μm porous hydrogels did the VEGF expression play a role in preventing vessel regression and helping to sustain the number of vessels present from three to six weeks. Regardless, pore size seemed to be the dominant factor in determining the angiogenic response with 60 μm porous hydrogels having more vessels present per area than 100 μm porous hydrogels at the initial onset of angiogenesis at three weeks. Increased pore rigidity may have been a key factor. The effect of porosity on wound healing was even more pronounced than what was observed in the subcutaneous implants. 100 and 60 μm porous hydrogels allowed for significantly faster wound closure than nano-pore hydrogels, which did not degrade and essentially provided a mechanical barrier to closure. Interestingly, total porosity and not specific pore size seemed to be the dominant factor in determining the wound closure rates. GFP-expressing transfected cells were present throughout the newly formed granulation tissue surrounding all hydrogel samples at two weeks. Transfection levels of pVEGF, however, did not seem to be high enough to enhance angiogenesis within the granulation tissue by statistically increasing vessel number, maturity, or size. Although the anticipated enhancement in angiogenesis in either model was not shown, the presence of transfected cells shows promise for the use of polyplex loaded porous hydrogels to produce a response in vivo. With further optimization we believe the proposed hydrogel system(s) has applications for controlled release of various DNA particles and other gene delivery vectors for in vivo tissue engineering and blood vessel formation.
Author: John A Packard
Publisher:
ISBN:
Category :
Languages : en
Pages : 110
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Book Description
Hyaluronic acid (HA) is a well-documented and frequently used macromolecule in bioengineering. Some of the many reasons for its common use include the variety of different modifications possible from the backbone, its prevalence in the body, and its versatility to be used in in vitro and in vivo applications. Using a one-step Diels-Alder reaction, HA was modified with Furfurylamine and used to create a hydrogel composed of HA modified with furan rings (HA-furan) crosslinked with Poly ethylene glycol modified with malemide ((MI)2PEG). In order to create different gel conditions, molecular weight (MW) of the HA used in the HA-furan was varied at low and high MW. Additionally, the mass percent within the gel was varied by altering the concentration of crosslinker within the gel based on the ratio between the Furans available within the gel and the malemides found in the (MI)2PEG. These variations created six different gel conditions, which showed that the physical properties such as swelling, stiffness, and degradation could be controlled and tuned based on the composition of the gel. The lessons learned from this study can be applied to creating and furthering the understanding of HA-furan gels and using them for in vitro cell studies.
Author: David Evered
Publisher: John Wiley & Sons
ISBN: 0470513780
Category : Science
Languages : en
Pages : 308
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Book Description
Presents state-of-the-art applications in hyaluronan research, from hyaluronan's physicochemical properties to its clinical role as a connective tissue marker and its surgical implications, particularly in ear, eye and orthopaedic surgery. Covers hyaluronan's synthesis and catabolism, its role in cells, its interactions with specific binding proteins, and its role in the embryonic nervous system.
