DOCSLIB.ORG

Cartilage Regeneration in Reinforced Gelatin-Based Hydrogels

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

BiofaBrication of implants for articular joint repair Cartilage regeneration in reinforced gelatin-based hydrogels Jetze Visser 2015 promotor Prof. dr. W.J.A. Dhert copromotoren Dr. ir. J. Malda Dr. ir. D. Gawlitta Biofabrication of implants for articular joint repair: Cartilage regeneration in reinforced gelatin-based hydrogels Jetze Visser PhD thesis, Utrecht University, University Medical Center Utrecht, Utrecht, the Netherlands Copyright © J. Visser 2015. All rights reserved. No parts of this thesis may be reproduced, stored in a retrieval system of any nature or transmitted in any form or by any means, without prior written consent of the author. The copyright of the articles that have been published has been transferred to the respective journals. Financial support for the printing of this thesis was generously provided by: De Nederlandse Orthopaedische Vereniging, the Dutch society for Biomaterials and Tissue Engineering, Anna Fonds te Leiden, Livit Orthopedie MRI Centrum and Chipsoft. The research in this thesis was financially supported by: the Netherlands Institute for Regenerative Medicine, the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n309962 (HydroZONES) and the Dutch Arthritis Foundation. ISBN 978-94-6169-706-6 Layout and printing: Optima Grafische Communicatie, Rotterdam, the Netherlands Cover design: Marco Bot Biofabrication of implants for articular joint repair Cartilage regeneration in reinforced gelatin-based hydrogels Bioprinten van implantaten voor het herstel van gewrichtsschade Kraakbeenregeneratie in verstevigde gelatine hydrogel (met een samenvatting in het Nederlands) proefschrift ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de rector magnificus, prof. dr. G.J. van der Zwaan, ingevolge het besluit van het college voor promoties in het openbaar te verdedigen op dinsdag 25 augustus 2015 des avonds te 6.00 uur door Jetze Visser geboren op 6 januari 1985 te Gaasterland this thesis is Based upon the following puBlications: Reinforcement of hydrogels using three-dimensionally printed microfibres. Visser J, Melchels FPW, Jeon JE, van Bussel EM, Kimpton LS, Byrne HM, Dhert WJA, Dalton PD, Hutmacher DW, Malda J. Nature Communications. 2015;6:6933 doi: 10.1038/ncomms7933 Crosslinkable Hydrogels derived from Cartilage, Meniscus and Tendon Tissue. Visser J, Levett PA, Te Moller NC, Besems J, Boere KW, Van Rijen MH, de Grauw JC, Dhert WJA, van Weeren PR, Malda J. Tissue Engineering Part A. 2015 Apr;21(7-8):1195-206 Endochondral bone formation in gelatin methacrylamide hydrogel with embedded cartilage-derived matrix particles. Visser J, Gawlitta D, Benders KE, Toma SM, Pouran B, van Weeren PR, Dhert WJA, Malda J. Biomaterials. 2015 Jan;37:174-182 Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers. Levato R, Visser J, Planell JA, Engel E, Malda J, Mateos-Timoneda MA. Biofabrication. 2014 Sep;6(3):035020 Covalent attachment of a three-dimensionally printed thermoplast to a gelatin hydrogel for mechanically enhanced cartilage constructs. Boere KW*, Visser J*, Seyednejad H, Rahimian S, Gawlitta D, van Steenbergen MJ, Dhert WJA, Hennink WE, Vermonden T, Malda J. Acta Biomaterialia. 2014 Jun;10(6):2602-11 *Authors contributed equally to this manuscript Weefsel uit de printer: de mogelijkheden van 3D-printen in de geneeskunde. Visser J, Melchels FP, Dhert WJ, Malda J. Nederlands Tijdschrijft voor Geneeskunde. 2013;157(52):A7043 Engineering hydrogels for biofabrication. Malda J, Visser J, Melchels FP, Jüngst T, Hennink WE, Dhert WJA, Groll J, Hutmacher DW. Advanced Materials. 2013 Sep;25(36):5011-28 Biofabrication of multi-material anatomically shaped tissue constructs. Visser J, Peters B, Burger TJ, Boomstra J, Dhert WJ, Melchels FP, Malda J. Biofabrication. 2013 Sep;5(3):035007 taBle of contents introduction Chapter 1 General introduction, outline and research questions 9 Chapter 2 Engineering hydrogels for biofabrication 27 part i Biological improvement of gelMA hydrogel with tissue-derived matrices Chapter 3 Crosslinkable hydrogels derived from cartilage, meniscus and tendon tissue 61 Chapter 4 Endochondral bone formation in gelatin methacrylamide hydrogel with 81 embedded cartilage-derived matrix particles part II mechanical improvement of gelMA hydrogel constructs with 3d-printed scaffolds Chapter 5 Covalent attachment of a three-dimensionally printed thermoplast to a gelatin 103 hydrogel for mechanically enhanced cartilage constructs Chapter 6 Reinforcement of hydrogels with three-dimensionally printed microfibres 127 Chapter 7 Preliminary results of a translational animal model 153 Cartilage repair with a combination of chondrons and MSCs in gelatin methacrylamide hydrogel: the establishment of an equine model part III Biofabrication of complex shaped constructs from gelMA for osteochondral tissue repair Chapter 8 Biofabrication of multi-material anatomically shaped tissue constructs 171 Chapter 9 Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers 187 Chapter 10 Preliminary results of a translational animal model 207 Biofabrication of anatomically shaped implants for regeneration of the rabbit humeral head discussion and summary Chapter 11 General discussion and future perspectives 221 References 237 List of abbreviations 265 Summary and answers to the research questions 271 Nederlandse samenvatting 281 Papers not included in this thesis 289 Acknowlegements/Dankwoord 291 Curriculum Vitae 295 Chapter 1 General Introduction, Outline and Research Questions This introduction was partially based on the following publication: Visser J, Melchels FP, Dhert WJ, Malda J. Weefsel uit de printer: de mogelijkheden van 3D-printen in de geneeskunde. [Tissue printing: the potential application of 3D printing in medicine]. Nederlands Tijdschrift voor Geneeskunde. 2013;157(52):A7043. Introduction 11 introduction regenerative medicine The acute or chronic degeneration of tissues in the human body can be regarded as the fundamental cause for morbidity and mortality1. All tissues degenerate over time, only some regenerate (heal) better than others. For example, a small skin laceration or stable bone fracture is likely to heal spontaneously. In contrast, heart and brain tissue have poor regenerative capacities, which becomes clinically evident by organ failure after hypoxia2,3. Cartilage is another tissue with very limited healing capacities, as no nerves and blood vessels are present to initiate regeneration4. Therefore, cartilage defects can occur already in young patients, usually as a result of acute degeneration5,6. Chronic degeneration of cartilage is a common problem in middle-aged and older patients: a disease known as osteoarthritis7. The field of regenerative medicine aims to assist the body to restore the function of an injured tissue. Traditionally, the development of regenerative therapies relies on the engineering of tissues by a combination of cells, growth factors and biomaterials8,9. Based on these principles, the first regenerative therapies for the repair of focal cartilage defects have already been implemented in health care6. Multiple disciplines contribute to further development of regenerative medicine. Advances in stem cell research offer increasing knowledge on the differentiation of multipotent mesenchymal stromal cells (MSCs) as the cellular component of regenera- tive therapies10. In addition, advances in the field of biomaterials and bioengineering have yielded materials and techniques to potentially create implants with biological and mechanical compatibility for the regeneration of tissues11,12. This chapter is an introduction to cartilage tissue, its acute and chronic degeneration and the current options and challenges in treatment. Next, biofabrication is introduced as a tool for the engineering of implants in regenerative medicine. This chapter con- cludes with research questions that focus on the biofabrication of implants for articular joint repair. articular cartilage tissue In every articulating joint, the long bones are covered by a layer of cartilage that pro- vides smooth articulation and shock absorption. Cartilage is avascular and aneural, and separated from the underlying bone by a calcified cartilage zone and a tidemark layer13. Therefore, nutrition of the cartilage tissue predominantly depends on the synovial fluid. The unique mechanical properties of cartilage can be ascribed to its specific extracel- lular matrix (ECM) composition, being water (70%), within a network of collagen type II and proteoglycans13. Chondrocytes are the only residing cells. A superficial, transitional 12 Chapter 1 and bottom zone can be identified in cartilage, based on its ECM composition, collagen alignment and chondrocyte subtype14. For example, collagen type II fibers form an organized matrix with an arching align- ment, resulting in fibers perpendicular to the articulating surface in the bottom layer and parallel to the surface in the superficial layer (Fig. 1)15. The superficial collagen fibers provide the highest stiffness and tensile strength, which gradually decreases in the transitional and bottom layer14. The compressive strength of cartilage tissue is mainly provided by the fluid pressurization of the proteoglycan matrix16. Proteoglycans are large proteins with attached glycosaminoglycans (GAGs), which surround the collagen matrix. As GAGs are negatively charged, they attract positive ions, which in turn resorb and retain water in the cartilage tissue13.
Recommended publications
  • Three-Dimensional Polycaprolactone Scaffold-Conjugated Bone

    Three-Dimensional Polycaprolactone Scaffold-Conjugated Bone

    Three-dimensional polycaprolactone scaffold-conjugated bone morphogenetic protein-2 promotes cartilage regeneration from primary chondrocytes in vitro and in vivo without accelerated endochondral ossification Claire G. Jeong,1 Huina Zhang,1 Scott J. Hollister1,2,3 1Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109-2125 2Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan 48109-2125 3Department of Surgery, The University of Michigan, Ann Arbor, Michigan 48109-0329 Received 16 August 2011; accepted 30 August 2011 Published online 21 May 2012 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.33249 Abstract: As articular cartilage is avascular, and mature chon- rolactone (PCL) scaffolds with chemically conjugated BMP-2. drocytes do not proliferate, cartilage lesions have a limited The results show that chemically conjugated BMP-2 PCL scaf- capacity for regeneration after severe damage. The treatment folds can promote significantly greater cartilage regeneration of such damage has been challenging due to the limited from seeded chondrocytes both in vitro and in vivo compared availability of autologous healthy cartilage and lengthy and with untreated scaffolds. Furthermore, our results demonstrate expensive cell isolation and expansion procedures. Hence, that the conjugated BMP-2 does not particularly accelerate the use of bone morphogenetic protein-2 (BMP-2), a potent endochondral ossification even in a readily permissible and regulator of chondrogenic expression,
  • Emerging Strategies of Bone and Joint Repair Olaf Schultz, Michael Sittinger, Thomas Haeupl and Gerd R Burmester Humboldt-University of Berlin, Berlin, Germany

    Emerging Strategies of Bone and Joint Repair Olaf Schultz, Michael Sittinger, Thomas Haeupl and Gerd R Burmester Humboldt-University of Berlin, Berlin, Germany

    http://arthritis-research.com/content/2/6/433 Commentary Emerging strategies of bone and joint repair Olaf Schultz, Michael Sittinger, Thomas Haeupl and Gerd R Burmester Humboldt-University of Berlin, Berlin, Germany Received: 23 March 2000 Arthritis Res 2000, 2:433–436 Revisions requested: 26 May 2000 The electronic version of this article can be found online at Revisions received: 29 June 2000 http://arthritis-research.com/content/2/6/433 Accepted: 17 July 2000 Published: 10 August 2000 © Current Science Ltd (Print ISSN 1465-9905; Online ISSN 1465-9913) Abstract The advances in biomedicine over the past decade have provided revolutionary insights into molecules that mediate cell proliferation and differentiation. Findings on the complex interplay of cells, growth factors, matrix molecules and cell adhesion molecules in the process of tissue patterning have vitalized the revolutionary approach of bioregenerative medicine and tissue engineering. Here we review the impact of recent work in this interdisciplinary field on the treatment of musculoskeletal disorders. This novel concept combines the transplantation of pluripotent stem cells, and the use of specifically tailored biomaterials, arrays of bioactive molecules and gene transfer technologies to direct the regeneration of pathologically altered musculoskeletal tissues. Keywords: biomaterials, genetic engineering, morphogenic factors, tissue engineering Introduction cells, a supportive matrix and bioactive molecules promot- During the past decade new and exciting strategies have ing differentiation and regeneration. The strategy of a emerged that will revolutionize the treatment of patients directed regeneration of musculoskeletal tissue damaged suffering from failure of vital structures. The science fiction by trauma, chronic inflammation or degeneration will per- scenario of regenerating damaged organs or even creating fectly supplement the treatment, once approved, with the a completely new tissue was brought to life with the new biological therapeutics in rheumatology.
  • Engineering Cartilage Tissue ☆ ⁎ Cindy Chung, Jason A

    Engineering Cartilage Tissue ☆ ⁎ Cindy Chung, Jason A

    Available online at www.sciencedirect.com Advanced Drug Delivery Reviews 60 (2008) 243–262 www.elsevier.com/locate/addr Engineering cartilage tissue ☆ ⁎ Cindy Chung, Jason A. Burdick Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 S. 33rd Street, Philadelphia, PA 19104, USA Received 19 July 2007; accepted 2 August 2007 Available online 5 October 2007 Abstract Cartilage tissue engineering is emerging as a technique for the regeneration of cartilage tissue damaged due to disease or trauma. Since cartilage lacks regenerative capabilities, it is essential to develop approaches that deliver the appropriate cells, biomaterials, and signaling factors to the defect site. The objective of this review is to discuss the approaches that have been taken in this area, with an emphasis on various cell sources, including chondrocytes, fibroblasts, and stem cells. Additionally, biomaterials and their interaction with cells and the importance of signaling factors on cellular behavior and cartilage formation will be addressed. Ultimately, the goal of investigators working on cartilage regeneration is to develop a system that promotes the production of cartilage tissue that mimics native tissue properties, accelerates restoration of tissue function, and is clinically translatable. Although this is an ambitious goal, significant progress and important advances have been made in recent years. © 2007 Elsevier B.V. All rights reserved. Keywords: Cartilage; Tissue engineering; Biomaterials; Stem cells; Regeneration Contents
  • Design of Artificial Extracellular Matrices for Tissue Engineering

    Design of Artificial Extracellular Matrices for Tissue Engineering

    Progress in Polymer Science 36 (2011) 238–268 Contents lists available at ScienceDirect Progress in Polymer Science journal homepage: www.elsevier.com/locate/ppolysci Design of artificial extracellular matrices for tissue engineering Byung-Soo Kim a,1, In-Kyu Park b,1, Takashi Hoshiba c, Hu-Lin Jiang d, Yun-Jaie Choi e, Toshihiro Akaike f,∗, Chong-Su Cho e,∗∗ a School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, South Korea b Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 501-746, South Korea c Biomaterials Center, National Institute for Materials Science, Tsukuba 305-0044, Japan d College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea e Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea f Department of Biomolecular Engineering, Tokyo Institute of Technology, Yokohama 226-8501, Japan article info abstract Article history: The design of artificial extracellular matrix (ECM) is important in tissue engineering because Received 25 May 2010 artificial ECM regulates cellular behaviors, including proliferation, survival, migration, Received in revised form and differentiation. Artificial ECMs have several functions in tissue engineering, includ- 22 September 2010 ing provision of cell-adhesive substrate, control of three-dimensional tissue structure, and Accepted 7 October 2010 Available online 20 October 2010 presentation of growth factors, cell-adhesion signals, and mechanical signals. Design cri- teria for artificial ECMs vary considerably depending on the type of the engineered tissue. This article reviews the materials and methods that have been used in fabrication of artifi- Keywords: Artificial extracellular matrix cial ECMs for engineering of specific tissues, including liver, cartilage, bone, and skin.
  • A Human Osteochondral Tissue Model Mimicking Cytokine-Induced Key Features of Arthritis in Vitro

    A Human Osteochondral Tissue Model Mimicking Cytokine-Induced Key Features of Arthritis in Vitro

    International Journal of Molecular Sciences Article A Human Osteochondral Tissue Model Mimicking Cytokine-Induced Key Features of Arthritis In Vitro Alexandra Damerau 1,2 , Moritz Pfeiffenberger 1,2, Marie-Christin Weber 1 , Gerd-Rüdiger Burmester 1,2, Frank Buttgereit 1,2, Timo Gaber 1,2,*,† and Annemarie Lang 1,2,† 1 Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, 10117 Berlin, Germany; [email protected] (A.D.); [email protected] (M.P.); [email protected] (M.-C.W.); [email protected] (G.-R.B.); [email protected] (F.B.); [email protected] (A.L.) 2 German Rheumatism Research Centre (DRFZ) Berlin, a Leibniz Institute, 10117 Berlin, Germany * Correspondence: [email protected] † These authors contributed equally. Abstract: Adequate tissue engineered models are required to further understand the (patho)physiol- ogical mechanism involved in the destructive processes of cartilage and subchondral bone during rheumatoid arthritis (RA). Therefore, we developed a human in vitro 3D osteochondral tissue model (OTM), mimicking cytokine-induced cellular and matrix-related changes leading to cartilage degra- dation and bone destruction in order to ultimately provide a preclinical drug screening tool. To this end, the OTM was engineered by co-cultivation of mesenchymal stromal cell (MSC)-derived bone and cartilage components in a 3D environment.
  • Guiding Chondrogenesis Through Controlled Growth Factor Presentation with Polymer Microspheres in High Density Stem Cell Systems

    Guiding Chondrogenesis Through Controlled Growth Factor Presentation with Polymer Microspheres in High Density Stem Cell Systems

    GUIDING CHONDROGENESIS THROUGH CONTROLLED GROWTH FACTOR PRESENTATION WITH POLYMER MICROSPHERES IN HIGH DENSITY STEM CELL SYSTEMS by LORAN DENISE SOLORIO Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Dissertation Advisor: Eben Alsberg Department of Biomedical Engineering CASE WESTERN RESERVE UNIVERSITY May 2012 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of Loran Denise Solorio candidate for the Ph.D degree*. (signed) Eben Alsberg (chair of the committee) Jean Welter Melissa Knothe Tate Edward Greenfield Arnold Caplan (date) Jan. 10, 2012 *We also certify that written approval has been obtained for any proprietary material contained therein. To my husband, Luis, my sister, Eran, and my parents Table of Contents Table of Contents.......................................................................................................... 1 List of Tables................................................................................................................. 4 List of Figures............................................................................................................... 5 Acknowledgements....................................................................................................... 7 List of Abbreviations.................................................................................................... 8 Abstract.........................................................................................................................
  • Key Regulatory Molecules of Cartilage Destruction in Rheumatoid Arthritis

    Key Regulatory Molecules of Cartilage Destruction in Rheumatoid Arthritis

    Available online http://arthritis-research.com/content/10/1/R9 ResearchVol 10 No 1 article Open Access Key regulatory molecules of cartilage destruction in rheumatoid arthritis: an in vitro study Kristin Andreas1, Carsten Lübke2, Thomas Häupl2, Tilo Dehne2, Lars Morawietz3, Jochen Ringe1, Christian Kaps4 and Michael Sittinger2 1Tissue Engineering Laboratory and Berlin – Brandenburg Center for Regenerative Therapies, Department of Rheumatology, Charité – Universitätsmedizin Berlin, Tucholskystrasse 2, 10117 Berlin, Germany 2Tissue Engineering Laboratory, Department of Rheumatology, Charité – Universitätsmedizin Berlin, Tucholskystrasse 2, 10117 Berlin, Germany 3Institute for Pathology, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany 4TransTissueTechnologies GmbH, Tucholskystrasse 2, 10117 Berlin, Germany Corresponding author: Kristin Andreas, [email protected] Received: 13 Jul 2007 Revisions requested: 21 Aug 2007 Revisions received: 28 Dec 2007 Accepted: 18 Jan 2008 Published: 18 Jan 2008 Arthritis Research & Therapy 2008, 10:R9 (doi:10.1186/ar2358) This article is online at: http://arthritis-research.com/content/10/1/R9 © 2008 Andreas et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons. Attribution License (http://creativecommons.org/licenses/by/ 2.0), which permits unrestricted. use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background Rheumatoid arthritis (RA) is a chronic,
  • The Tlinical Efficacy of Autologous Concentrated

    The Tlinical Efficacy of Autologous Concentrated

    Published online: 2020-04-26 NUJHS Vol. 4, No.3, September 2014, ISSN 2249-7110 Nitte University Journal of Health Science Original Article THE CLINICAL EFFICACY OF AUTOLOGOUS CONCENTRATED PLATELETS IN TREATMENT OF TMJ DISORDERS - A PILOT STUDY S.M. Sharma1 & Dhruvit Thakar2 1Head of the Department, 2Junior Resident, Department of Oral and Maxillofacial Surgery A.B. Shetty Memorial Institute of Dental Sciences, Nitte University, Mangalore - 575 018 Karnataka, India. Correspondence : Dhruvit Thakar Junior Resident, Department of Oral and Maxillofacial Surgery A.B. Shetty Memorial Institute of Dental Sciences, Nitte University, Mangalore - 575 018, Karnataka, India. Mobile : +91 97425 59615 E-mail : [email protected] Abstract: Platelet rich plasma is a natural concentrate of autologous blood growth factor which is obtained by sequestering and concentrating platelets by gradient density centrifugation experimented in different fields of medicine in order to test its potential to enhance tissue regeneration. These platelets when activated undergo degranulation to release growth factors with healing properties. It also contains plasma, cytokines, thrombin, and other growth factors that are implicated in wound healing and have inherent biological and adhesive properties. The aim of the study is to explore a novel approach to treat degenerative lesion of the articular cartilage of temporomandibular joint. Patients with chronic degenerative conditions of the joint, were treated with intra articular PRP injections. The procedure involved collection of 10 ml of venous blood and twice centrifuged to obtain 2 ml of PRP which was used for injection after activation by calcium chloride. The patients were clinically prospectively evaluated before and at the end of the treatment, and at 2, 4, and 6 months of follow up.
  • Ipscs in Modeling and Therapy of Osteoarthritis

    Ipscs in Modeling and Therapy of Osteoarthritis

    biomedicines Review iPSCs in Modeling and Therapy of Osteoarthritis Maria Csobonyeiova 1, Stefan Polak 1, Andreas Nicodemou 2 , Radoslav Zamborsky 3 and Lubos Danisovic 2,4,* 1 Institute of Histology and Embryology, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia; [email protected] (M.C.); [email protected] (S.P.) 2 Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia; [email protected] 3 National Institute of Children’s Diseases, Department of Orthopedics, Faculty of Medicine, Comenius University, Limbova 1, 833 40 Bratislava, Slovakia; [email protected] 4 Regenmed Ltd., Medena 29, 811 01 Bratislava, Slovakia * Correspondence: [email protected]; Tel.: +421-2-5935-7215 Abstract: Osteoarthritis (OA) belongs to chronic degenerative disorders and is often a leading cause of disability in elderly patients. Typically, OA is manifested by articular cartilage erosion, pain, stiffness, and crepitus. Currently, the treatment options are limited, relying mostly on pharmacological therapy, which is often related to numerous complications. The proper management of the disease is challenging because of the poor regenerative capacity of articular cartilage. During the last decade, cell-based approaches such as implantation of autologous chondrocytes or mesenchymal stem cells (MSCs) have shown promising results. However, the mentioned techniques face their hurdles (cell harvesting, low proliferation capacity). The invention of induced pluripotent stem cells (iPSCs) has created new opportunities to increase the efficacy of the cartilage healing process. iPSCs may represent an unlimited source of chondrocytes derived from a patient’s somatic cells, circumventing ethical and immunological issues.
  • A Novel, Self-Assembled Artificial Cartilage– Hydroxyapatite Conjugate

    A Novel, Self-Assembled Artificial Cartilage– Hydroxyapatite Conjugate

    Journal name: International Journal of Nanomedicine Article Designation: Original Research Year: 2019 Volume: 14 International Journal of Nanomedicine Dovepress Running head verso: Kumai et al Running head recto: Kumai et al open access to scientific and medical research DOI: 193963 Open Access Full Text Article ORIGINAL RESEARCH A novel, self-assembled artificial cartilage– hydroxyapatite conjugate for combined articular cartilage and subchondral bone repair: histopathological analysis of cartilage tissue engineering in rat knee joints This article was published in the following Dove Medical Press journal: International Journal of Nanomedicine Takanori Kumai1 Purpose: We previously created a self-assembled cartilage-like complex in vitro from only three Naoko Yui1 cartilage components, hyaluronic acid (HA), aggrecan (AG) and type II collagen, without other Kanaka Yatabe1 materials such as cross-linking agents. Based on this self-organized AG/HA/collagen complex, Chizuko Sasaki2 we have created three novel types of biphasic cartilage and bone-like scaffolds combined with Ryoji Fujii3 hydroxyapatite (HAP) for osteochondral tissue engineering. These scaffolds have been devel- Mitsuko Takenaga3 oped from self-assembled cartilage component molecules and HAP at the nanometer scale by manipulating the intermolecular relations. Hiroto Fujiya1 Patients and methods: The surface structure of each self-organized biphasic cartilage and Hisateru Niki4 bone-like scaffold was evaluated by scanning electron microscopy, whereas the viscoelasticity 3 Kazuo Yudoh was also analyzed in vitro. Three types of artificial cartilage–HAP conjugates were implanted 1Department of Sports Medicine, into an osteochondral defect in rat knee joints, and bone and cartilage tissues of the implanted St Marianna University School of site were examined 4 and 8 weeks after implantation.
  • Printer Capable of Producing Hybrid Hydrogel Based Artificial Cartilage

    Printer Capable of Producing Hybrid Hydrogel Based Artificial Cartilage

    Developing a 3D Printer Capable of Producing Hybrid Hydrogel Based Artificial Cartilage Feldbush, Anna (School: West Shore Junior/Senior High School) More than 2 of every 100 Americans will require a joint replacement, as the population is surviving longer new strains on the human body are discovered. Knee replacements are required when the protective layer of cartilage is worn away from the joint’s surface causing bone damage. Unfortunately total knee replacements do not provide lifelong support for an injured joint. For younger patients artificial cartilage can provide an alternative to the total joint replacements. This project explores the modification of a commercial 3D printer in order to 3D print hydrogel artificial cartridge, with material properties similar to natural knee cartilage. Hybrid artificial cartilage solutions were created using gelatin and hydrogel base, composed of sodium alginate and calcium chloride. Both of these materials, while incapable of behaving as an artificial cartilage solution independently, can be used in conjunction to form functioning artificial cartilage. In order to modify the 3D printer, a pump system was designed to dispense the cartilage solution on the printing base. Print speed and other aspects of printing quality were manipulated to create viable samples. Multiple aspects of the artificial cartilage samples were tested and compared against pre existing data on articular cartilage. While none of the tested samples matched all of the parameters of natural cartilage both 7g/4g and 7g/2g show potential for mirroring the function of natural cartilage. The least squares regression line for water composition and cartilage density suggest the optimal solution proportion for gelatin to sodium alginate levels is between 2.73 and 3.62.
  • Friction of Polymer Gels O

    Friction of Polymer Gels O

    FRICTION OF POLYMER GELS O. Ronsin, T. Baumberger, C. Caroli Institut des NanoSciences de Paris - CNRS - Univ. Paris 6 Gels = soft elastic solid with high content of fluid = poroelastic solid ñ specific frictionnal properties ­ e.g. : gels in biological systems : very low friction (e.g. articular cartilage) ­ Network / solvent contributions to friction ? POROELASTIC EFFECTS : ARTICULAR CARTILAGE (COLLAGEN GEL) Poroelastic transfer of fluid across cartilage Ñ load supported by fluid at short times low friction : fluid lubrication Ñ increasing contribution of matrix as t Õ higher friction : solid friction Wfluid = 1 ¡ (1 ¡ ) µ µ8 φ µ Wtotal ¶ C. W. McCutchen, Wear 5, 1 (1959). G. A. Ateshian, Journal of Biomechanics 42, 1163 (2009). POLYMER GELS = + Æ ­ network chains cross-links (physical or chemical), distance ξ ­ solvent (90–99%), viscosity η η ñ "poro-elastic" material ­ elasticity of entropic origin (rubber) kBT 2 5 ξ G 10 – 10 Pa, ξ 3 – 30 nm. ξ3 ­ solvent/network relative motion ñ diffusive mode ¡ 9 ¡11 2 ¡1 Dcoll. 10 – 10 m .s for aqueous gels (10¡7m2.s¡1 for cartilage) 5 7 ñ 10 ¡ ¡10 s for 1 cm thick sample ñ get rid of time dependence of fluid loaded part. HYDRODYNAMIC FRICTION OF GELATIN GELS Model system : gelatin gel on clean flat glass in plane/plane contact. + Ñ control almost independently solvent viscosity ηS 1 ¡ 4 Pa.s (water glycerol) and network mesh size ξ 6 ¡ 12 nm (gelatin contentration c) gel glass impose ­ sliding velocity V (1 – 2000 µm/s) ­ normal pressure p (0 – 2 kPa) measure ­ stationnary frictionnal shear stress σ(V ).