The Experts below are selected from a list of 55980 Experts worldwide ranked by ideXlab platform
Jeroen Leijten - One of the best experts on this subject based on the ideXlab platform.
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bioinspired seeding of Biomaterials using three dimensional microtissues induces chondrogenic stem cell differentiation and cartilage formation under growth factor free conditions
Scientific Reports, 2016Co-Authors: L Moreira S Teixeira, Johanna Bolander, Bram Vanspauwen, Jeroen Lammertyn, Jeroen Leijten, Jan Schrooten, Wei Ji, Frank LuytenAbstract:Cell laden Biomaterials are archetypically seeded with individual cells and steered into the desired behavior using exogenous stimuli to control growth and differentiation. In contrast, direct cell-cell contact is instructive and even essential for natural tissue formation. Namely, microaggregation and condensation of mesenchymal progenitor cells triggers chondrogenesis and thereby drives limb formation. Yet a biomimetic strategy translating this approach into a cell laden Biomaterial-based therapy has remained largely unexplored. Here, we integrate the microenvironment of cellular condensation into Biomaterials by encapsulating microaggregates of a hundred human periosteumderived stem cells. This resulted in decreased stemness-related markers, up regulation of chondrogenic genes and improved in vivo cartilage tissue formation, as compared to single cell seeded Biomaterials. Importantly, even in the absence of exogenous growth factors, the microaggregate laden hydrogels outperformed conventional single cell laden hydrogels containing supraphysiological levels of the chondrogenic growth factor TGFB. Overall, the bioinspired seeding strategy described herein represents an efficient and growth factor-free approach to efficiently steer cell fate and drive tissue formation for Biomaterial-based tissue engineering strategies.
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Enzymatic Crosslinking of Polymer Conjugates is Superior over Ionic or UV Crosslinking for the On-Chip Production of Cell-Laden Microgels
Macromolecular Bioscience, 2016Co-Authors: Sieger Henke, Evelien W. M. Kemna, A.a. Van Apeldoorn, M. Neubauer, Jeroen Leijten, Andreas Fery, Albert Van Den Berg, Hermanus Bernardus Johannes KarperienAbstract:Cell-laden micrometer-sized hydrogels (microgels) hold great promise for improving high throughput ex- vivo drug screening and engineering biomimetic tissues. Microfluidics is a powerful tool to produce microgels. However, only a limited amount of Biomaterials have been reported to be compatible with on-chip microgel formation. Moreover, these Biomaterials are often associated with mechanical instability, cytotoxicity, and cellular senescence. To resolve this challenge, dextran-tyramine has been explored as a novel Biomaterial for on-chip microgel formation. In particular, dextran-tyramine is compared with two commonly used Biomaterials, namely, polyethylene-glycol diacrylate (PEGDA) and alginate, which crosslink through enzymatic reaction, UV polymerization, and ionic interaction, respectively. Human mesenchymal stem cells (hMSCs) encapsulated in dextran-tyramine microgels demonstrate significantly higher (95%) survival as compared to alginate (81%) and PEGDA (69%). Long-term cell cultures demonstrate that hMSCs in PEGDA microgels become senescent after 7 d. Alginate microgels dissolve within 7 d due to Ca2+ loss. In contrast, dextran-tyramine based microgels remain stable, sustain hMSCs metabolic activity, and permit for single-cell level analysis for at least 28 d of culture. In conclusion, enzymatically crosslinking dextran-tyramine conjugates represent a novel Biomaterial class for the on-chip production of cell-laden microgels, which possesses unique advantages as compared to the commonly used UV and ionic crosslinking Biomaterials.
Robert Klopfleisch - One of the best experts on this subject based on the ideXlab platform.
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The pathology of the foreign body reaction against Biomaterials.
Journal of Biomedical Materials Research Part A, 2016Co-Authors: Robert Klopfleisch, Friedrich JungAbstract:The healing process after implantation of Biomaterials involves the interaction of many contributing factors. Besides their in vivo functionality, Biomaterials also require characteristics that allow their integration into the designated tissue without eliciting an overshooting foreign body reaction (FBR). The targeted design of Biomaterials with these features, thus, needs understanding of the molecular mechanisms of the FBR. Much effort has been put into research on the interaction of engineered materials and the host tissue. This elucidated many aspects of the five FBR phases, that is protein adsorption, acute inflammation, chronic inflammation, foreign body giant cell formation, and fibrous capsule formation. However, in practice, it is still difficult to predict the response against a newly designed Biomaterial purely based on the knowledge of its physical-chemical surface features. This insufficient knowledge leads to a high number of factors potentially influencing the FBR, which have to be analyzed in complex animal experiments including appropriate data-based sample sizes. This review is focused on the current knowledge on the general mechanisms of the FBR against Biomaterials and the influence of Biomaterial surface topography and chemical and physical features on the quality and quantity of the reaction. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 927-940, 2017.
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macrophage reaction against Biomaterials in the mouse model phenotypes functions and markers
Acta Biomaterialia, 2016Co-Authors: Robert KlopfleischAbstract:Abstract The foreign body reaction (FBR) is a response of the host tissue against more or less degradation-resistant foreign macromolecular material. The reaction is divided into five different phases which involve most aspects of the innate and the adaptive immune system: protein adsorption, acute and chronic inflammation, foreign body giant cell formation and fibrosis. It is long known, that macrophages play a central role in all of these phases except for protein adsorption. Initially it was believed that the macrophage driven FBR has a complete negative effect on biocompatibility. Recent progress in Biomaterial and macrophage research however describe macrophages as more than pure antigen phagocytosing and presenting cells and thus pro-inflammatory cells involved in Biomaterial encapsulation and failure. Quite contrary, both, pro-inflammatory M1 macrophages, the diverse regulatory M2 macrophage subtypes and even foreign body giant cells (FBGC) are after necessary for integration of non-degradable Biomaterials and degradation and replacement of degradable Biomaterials. This review gives a comprehensive overview on the taxonomy of the currently known macrophage subtypes. Their diverging functions, metabolism and markers are summarized and the relevance of this more diverse macrophage picture for the design of Biomaterials is shortly discussed. Statement of Significance The view on role of macrophages in the foreign body reaction against Biomaterials is rapidly changing. Despite the initial idea that macrophage are mainly involved in undesired degradation and Biomaterial rejection it becomes now clear that they are nevertheless necessary for proper integration of non-degradable Biomaterials and degradation of placeholder, degradable Biomaterials. As a pathologist I experienced a lack on a good summary on the current taxonomy, functions and phenotypes of macrophages in my recent projects on the biocompatibility of Biomaterials in the mouse model. The submitted review therefore intends to gives a comprehensive overview on the taxonomy of the currently known macrophage subtypes. Their diverging functions, metabolism and markers are summarized and the relevance of this more diverse macrophage picture for the design of Biomaterials is shortly discussed.
Michael Glogauer - One of the best experts on this subject based on the ideXlab platform.
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Macrophages, foreign body giant cells and their response to implantable Biomaterials
Materials, 2015Co-Authors: Zeeshan Sheikh, Oriyah Barzilay, Noah Fine, Patricia J. Brooks, Michael GlogauerAbstract:All Biomaterials, when implanted in vivo, elicit cellular and tissue responses. These responses include the inflammatory and wound healing responses, foreign body reactions, and fibrous encapsulation of the implanted materials. Macrophages are myeloid immune cells that are tactically situated throughout the tissues, where they ingest and degrade dead cells and foreign materials in addition to orchestrating inflammatory processes. Macrophages and their fused morphologic variants, the multinucleated giant cells, which include the foreign body giant cells (FBGCs) are the dominant early responders to Biomaterial implantation and remain at Biomaterial-tissue interfaces for the lifetime of the device. An essential aspect of macrophage function in the body is to mediate degradation of bio-resorbable materials including bone through extracellular degradation and phagocytosis. Biomaterial surface properties play a crucial role in modulating the foreign body reaction in the first couple of weeks following implantation. The foreign body reaction may impact biocompatibility of implantation devices and may considerably impact short- and long-term success in tissue engineering and regenerative medicine, necessitating a clear understanding of the foreign body reaction to different implantation materials. The focus of this review article is on the interactions of macrophages and foreign body giant cells with Biomaterial surfaces, and the physical, chemical and morphological characteristics of Biomaterial surfaces that play a role in regulating the foreign body response. Events in the foreign body response include protein adsorption, adhesion of monocytes/macrophages, fusion to form FBGCs, and the consequent modification of the Biomaterial surface. The effect of physico-chemical cues on macrophages is not well known and there is a complex interplay between Biomaterial properties and those that result from interactions with the local environment. By having a better understanding of the role of macrophages in the tissue healing processes, especially in events that follow Biomaterial implantation, we can design novel Biomaterials-based tissue-engineered constructs that elicit a favorable immune response upon implantation and perform for their intended applications.
Liping Tang - One of the best experts on this subject based on the ideXlab platform.
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molecular basis of Biomaterial mediated foreign body reactions
Blood, 2001Co-Authors: Wenjing Hu, Tatiana P Ugarova, John W. Eaton, Liping TangAbstract:Despite being inert and nontoxic, implanted Biomaterials often trigger adverse foreign body reactions such as inflammation, fibrosis, infection, and thrombosis. With regard to the inflammatory responses to Biomaterial implants, it was previously found that a crucial precedent event was the spontaneous adsorption and denaturation of fibrinogen on implant surfaces. It was further found that interactions between the phagocyte integrin Mac-1 (CD11b/CD18) and one short sequence within the fibrinogen D domain (γ190-202; P1) at least partially explained phagocyte accumulation on implant surfaces. However, the reason that adsorbed fibrinogen is proinflammatory—while soluble fibrinogen clearly is not—remained obscure. In this study, therefore, the question of how fibrinogen is converted to a proinflammatory state when adsorbed to Biomaterial surfaces is investigated. In soluble fibrinogen, the 13 amino acid P1 sequence was found to be hidden. However, the adsorption and denaturation of fibrinogen on the surfaces of commonly used Biomaterials lead to the exposure of P1 and a second neo-epitope, γ377-395 (P2), which also interacts with Mac-1 and is similarly occult in the soluble protein. The extent of Biomaterial-mediated P1 and P2 exposure appears directly related to the severity of inflammatory responses to a test panel of Biomaterials. Finally, thrombin-mediated conversion of fibrinogen to fibrin also exposes both P1 and P2 epitopes. These observations may help explain both the inflammation caused by many types of implanted Biomaterials and that which occurs naturally following thrombotic events.
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mast cells mediate acute inflammatory responses to implanted Biomaterials
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Liping Tang, Timothy A Jennings, John W. EatonAbstract:Implanted Biomaterials trigger acute and chronic inflammatory responses. The mechanisms involved in such acute inflammatory responses can be arbitrarily divided into phagocyte transmigration, chemotaxis, and adhesion to implant surfaces. We earlier observed that two chemokines-macrophage inflammatory protein 1alpha/monocyte chemoattractant protein 1-and the phagocyte integrin Mac-1 (CD11b/CD18)/surface fibrinogen interaction are, respectively, required for phagocyte chemotaxis and adherence to Biomaterial surfaces. However, it is still not clear how the initial transmigration of phagocytes through the endothelial barrier into the area of the implant is triggered. Because implanted Biomaterials elicit histaminic responses in the surrounding tissue, and histamine release is known to promote rapid diapedesis of inflammatory cells, we evaluated the possible role of histamine and mast cells in the recruitment of phagocytes to Biomaterial implants. Using i.p. and s. c. implantation of polyethylene terephthalate disks in mice we find: (i) Extensive degranulation of mast cells, accompanied by histamine release, occurs adjacent to short-term i.p. implants. (ii) Simultaneous administration of H1 and H2 histamine receptor antagonists (pyrilamine and famotidine, respectively) greatly diminishes recruitment and adhesion of both neutrophils (<20% of control) and monocytes/macrophages (<30% of control) to implants. (iii) Congenitally mast cell-deficient mice also exhibit markedly reduced accumulation of phagocytes on both i.p. and s.c implants. (iv) Finally, mast cell reconstitution of mast cell-deficient mice restores "normal" inflammatory responses to Biomaterial implants. We conclude that mast cells and their granular products, especially histamine, are important in recruitment of inflammatory cells to Biomaterial implants. Improved knowledge of such responses may permit purposeful modulation of both acute and chronic inflammation affecting implanted Biomaterials.
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mast cells mediate acute inflammatory responses to implanted Biomaterials histamineyphagocytes
1998Co-Authors: Liping Tang, Imothy T A Jennings, John W. EatonAbstract:Implanted Biomaterials trigger acute and chronic inf lammatory responses. The mechanisms involved in such acute inf lammatory responses can be arbitrarily divided into phagocyte transmigration, chemotaxis, and adhesion to implant surfaces. We earlier observed that two chemokines— macrophage inf lammatory protein 1aymonocyte chemoat- tractant protein 1—and the phagocyte integrin Mac-1 (CD11byCD18)ysurface fibrinogen interaction are, respec- tively, required for phagocyte chemotaxis and adherence to Biomaterial surfaces. However, it is still not clear how the initial transmigration of phagocytes through the endothelial barrier into the area of the implant is triggered. Because implanted Biomaterials elicit histaminic responses in the surrounding tissue, and histamine release is known to pro- mote rapid diapedesis of inf lammatory cells, we evaluated the possible role of histamine and mast cells in the recruitment of phagocytes to Biomaterial implants. Using i.p. and s.c. im- plantation of polyethylene terephthalate disks in mice we find: (i) Extensive degranulation of mast cells, accompanied by histamine release, occurs adjacent to short-term i.p. implants. (ii) Simultaneous administration of H1 and H2 histamine receptor antagonists (pyrilamine and famotidine, respec- tively) greatly diminishes recruitment and adhesion of both neutrophils (<20% of control) and monocytesymacrophages (<30% of control) to implants. (iii) Congenitally mast cell- deficient mice also exhibit markedly reduced accumulation of phagocytes on both i.p. and s.c implants. (iv) Finally, mast cell reconstitution of mast cell-deficient mice restores ''normal'' inf lammatory responses to Biomaterial implants. We con- clude that mast cells and their granular products, especially histamine, are important in recruitment of inf lammatory cells to Biomaterial implants. Improved knowledge of such re- sponses may permit purposeful modulation of both acute and chronic inf lammation affecting implanted Biomaterials.
Jie Li - One of the best experts on this subject based on the ideXlab platform.
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colony stimulating factor 1 receptor is a central component of the foreign body response to Biomaterial implants in rodents and non human primates
Nature Materials, 2017Co-Authors: Joshua C Doloff, Arturo J Vegas, Omid Veiseh, Shady Farah, Jie LiAbstract:Host recognition and immune-mediated foreign body response to Biomaterials can compromise the performance of implanted medical devices. To identify key cell and cytokine targets, here we perform in-depth systems analysis of innate and adaptive immune system responses to implanted Biomaterials in rodents and non-human primates. While macrophages are indispensable to the fibrotic cascade, surprisingly neutrophils and complement are not. Macrophages, via CXCL13, lead to downstream B cell recruitment, which further potentiated fibrosis, as confirmed by B cell knockout and CXCL13 neutralization. Interestingly, colony stimulating factor-1 receptor (CSF1R) is significantly increased following implantation of multiple Biomaterial classes: ceramic, polymer and hydrogel. Its inhibition, like macrophage depletion, leads to complete loss of fibrosis, but spares other macrophage functions such as wound healing, reactive oxygen species production and phagocytosis. Our results indicate that targeting CSF1R may allow for a more selective method of fibrosis inhibition, and improve Biomaterial biocompatibility without the need for broad immunosuppression. By studying the immune responses of animals to different types of Biomaterial implants, colony stimulating factor-1 receptor is revealed as an important mediator of the foreign body reaction and a possible target for fibrosis inhibition.
