DOCSLIB.ORG

Tendon Extracellular Matrix: Tenogenic Activity on Mesenchymal Stem Cells and Utility in Tendon Tissue Engineering

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Tendon Extracellular Matrix: Tenogenic Activity on Mesenchymal Stem Cells and Utility in Tendon Tissue Engineering TENDON EXTRACELLULAR MATRIX: TENOGENIC ACTIVITY ON MESENCHYMAL STEM CELLS AND UTILITY IN TENDON TISSUE ENGINEERING by Guang Yang Bachelor of Science, University of Science and Technology of China, 2010 Submitted to the Graduate Faculty of Swanson School of Engineering in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Pittsburgh 2015 UNIVERSITY OF PITTSBURGH SWANSON SCHOOL OF ENGINEERING This dissertation was presented by Guang Yang It was defended on December 1st, 2015 and approved by Johnny Huard, Ph.D., Professor, Department of Orthopaedic Surgery Nam Vo, Ph.D., Assistant Professor, Department of Orthopaedic Surgery William R. Wagner, Ph.D., Professor, Department of Bioengineering and Chemical Engineering Dissertation Director: Rocky S. Tuan, Ph.D., Department of Orthopaedic Surgery and Bioengineering ii Copyright © by Guang Yang 2015 iii TENDON EXTRACELLULAR MATRIX: TENOGENIC ACTIVITY ON MESENCHYMAL STEM CELLS AND UTILITY IN TENDON TISSUE ENGINEERING Guang Yang, Ph.D. University of Pittsburgh, 2015 Because of the limited and unsatisfactory outcomes of clinical tendon repair, tissue engineering approaches using adult mesenchymal stem cells (MSCs) are being considered a promising alternative healing strategy for injured tendon tissues. Successful and functional tendon tissue engineering depends on harnessing the biochemical cues presented by the native tendon extracellular matrix (ECM) and the embedded tissue-specific bio-factors. We have prepared and characterized the biological activities of a soluble extract of decellularized tendon ECM (tECM) on adult adipose derived stem cells (ASCs) on the basis of histological, biochemical, and gene expression analyses. Our results revealed the tenogenic effect of tECM on hASCs cultured in a 3-dimensional (3D) collagen scaffold under uniaxial tension. The presence of tECM also suppressed the osteogenic differentiation of hASCs induced by uniaxial tension and enhanced scaffold mechanical strength, accompanied by reduced expression and activity of matrix metalloproteinases (MMPs). Furthermore, we found that tECM enhanced the proliferation and TGF-β3 induced tenogenesis of ASCs, and modulated matrix deposition and organization by ASCs seeded in 3D fibrous scaffolds. These findings support the utility of tECM in creating bio- functional scaffolds for tendon tissue engineering. We also report here the development of a novel composite fibrous scaffold as a tendon graft fabricated by co-electrospinning of poly-ε- iv caprolactone (PCL) and methacrylated gelatin (mGLT), which allowed the encapsulation of ASCs within the scaffold upon visible light induced gelatin photo-crosslinking, as well as the formation of stable, crosslinked multi-layered constructs. This scaffold design may improve cell- based tendon regeneration by serving as an effective reservoir of tECM and tenogenic growth factors to recapitulate the structural and biochemical characteristics of native tendon tissue. Our findings should lead to translational tissue engineering applications that will improve patient outcomes in the context of clinical tendon repair. v TABLE OF CONTENTS PREFACE ................................................................................................................................. XIV 1.0 INTRODUCTION ........................................................................................................ 1 1.1 TENDON BIOLOGY .......................................................................................... 1 1.1.1 Development of tendon tissues........................................................................ 1 1.1.2 The structure and composition of tendon tissue ........................................... 7 1.1.3 Tendon injury and natural healing .............................................................. 12 1.2 TENDON TISSUE ENGINEERING ............................................................... 15 1.2.1 Cells ................................................................................................................. 16 1.2.2 Scaffolds .......................................................................................................... 19 1.2.3 Bioactive molecules ........................................................................................ 22 1.2.4 Mechanical stimulation ................................................................................. 24 1.3 RESEARCH OVERIVEW ............................................................................... 26 2.0 TENDON-DERIVED EXTRACELLULAR MATRIX ENHANCES TENOGENIC DIFFERENTIATION OF HUMAN ADIPOSE-DERIVED STEM CELLS CULTURED IN 3-DIMENSIONAL COLLAGEN SCAFFOLD UNDER TENSION .................................................................................................................... 28 2.1 ABSTRACT........................................................................................................ 28 2.2 INTRODUCTION ............................................................................................. 29 2.3 MATERIALS AND METHODS ...................................................................... 32 vi 2.3.1 Tissue harvest ................................................................................................. 32 2.3.2 Extraction of tECM ....................................................................................... 32 2.3.3 SDS-PAGE and Western blot assay ............................................................. 33 2.3.4 Cell isolation and culture .............................................................................. 34 2.3.5 3D culture of cells under static tension ........................................................ 34 2.3.6 Scanning electron microscopy (SEM) .......................................................... 35 2.3.7 Cell viability analysis ..................................................................................... 35 2.3.8 Histology ......................................................................................................... 36 2.3.9 Real-time PCR analysis ................................................................................. 37 2.3.10 Mechanical test ............................................................................................. 38 2.3.11 MMP activity assay ...................................................................................... 39 2.3.12 Statistical analysis ......................................................................................... 39 2.4 RESULTS ........................................................................................................... 40 2.4.1 Characteristics of tendon-derived ECM ...................................................... 40 2.4.2 Constructs and cell morphology ................................................................... 43 2.4.3 Cell viability and proliferation ..................................................................... 46 2.4.4 Cell differentiation ......................................................................................... 47 2.4.5 Mechanical properties of the scaffold .......................................................... 50 2.4.6 Gene expression and activity of MMPs ....................................................... 51 2.5 DISCUSSION ..................................................................................................... 52 2.6 CONCLUSIONS ................................................................................................ 58 3.0 TENDON-DERIVED EXTRACELLULAR MATRIX ENHANCES TGF-ΒETA 3 INDUCED TENOGENIC DIFFERENTIATION OF HUMAN ADIPOSE- DERIVED STEM CELLS ......................................................................................... 59 vii 3.1 ABSTRACT........................................................................................................ 59 3.2 INTRODUCTION ............................................................................................. 60 3.3 MATERIALS AND METHODS ...................................................................... 63 3.3.1 Cell isolation and culture .............................................................................. 63 3.3.2 Colony forming unit-fibroblast assay .......................................................... 63 3.3.3 Flow cytometry .............................................................................................. 64 3.3.4 Preparation of tendon ECM ......................................................................... 64 3.3.5 Preparation of scaffold .................................................................................. 65 3.3.6 Scanning electron microscopy (SEM) .......................................................... 65 3.3.7 Differentiation of hASCs ............................................................................... 65 3.3.8 Cell proliferation tests ................................................................................... 66 3.3.9 Real-time PCR analysis of gene expression ................................................. 67 3.3.10 Protein extraction and Western blot assay ................................................ 67 3.3.11 Mechanical testing ........................................................................................ 68 3.3.12 Matrix deposition and characterization ..................................................... 68 3.3.13 Immunofluorescent staining ........................................................................ 69 3.3.14 Statistical analysis
Load more

Recommended publications
  • Tendon Fibroblasts
    Ann Rheum Dis: first published as 10.1136/ard.46.5.385 on 1 May 1987. Downloaded from Annals of the Rheumatic Diseases, 1987; 46, 385-390 Isolation and growth characteristics of adult human tendon fibroblasts M D CHARD, J K WRIGHT, AND B L HAZLEMAN From the Rheumatology Research Unit, Addenbrooke's Hospital, Hills Road, Cambridge SUMMARY An explant method for the isolation of fibroblasts from adult human tendon is described. Cells were successfully isolated from 22 out of 27 common biceps tendons obtained from cadaveric donors (age range 11-83 years). The fibroblasts could be maintained in culture using standard methods and morphologically resembled those of synovial rather than dermal origin. Growth characteristics of 12 cell lines were assessed by deoxyribose nucleic acid (DNA) synthesis using [3H]thymidine incorporation in response to stimulation by fetal calf serum. Cells obtained separately from superficial and deep parts of the tendons produced almost identical responses. No significant reduction in growth response with increasing age was found when related to the age of the donor. Therefore this study did not show any age related defect in the short term tendon fibroblast replicative responses to serum. Key words: in vitro, DNA synthesis. copyright. Tendinous lesions are common, but their nature and other tissues such as skin. It is desirable to investi- any possible predisposing factors are not well gate adult human tendon fibroblasts directly. It was understood. They occur in middle life frequently thought that the culture of adult human tendon after only minor, if any, injury. The extent to which fibroblasts would be very difficult to achieve be- this reflects age related changes in tendon tissue is cause of the differentiated appearance of cells on uncertain.
    [Show full text]
  • Review the Cellular Matrix: a Feature of Tensile Bearing Dense Soft
    Histol Histopathol (2002) 17: 523-537 Histology and http://www.hh.um.es Histopathology Cellular and Molecular Biology Review The cellular matrix: a feature of tensile bearing dense soft connective tissues I.K. Lo, S. Chi, T. Ivie, C.B. Frank and J.B. Rattner Joint Injury and Arthritis Research Group, University of Calgary, Calgary, Canada S u m m a r y. The term connective tissue encompasses a recent studies using a variety of microscopic and indirect d iverse group of tissues that reside in diff e r e n t immunofluorescence techniques suggest that these e nvironments and must support a spectrum of apparently diverse groups of tissues, which are mechanical functions. Although the extracellular matrix characterized by a spectrum of functions and in vivo of these tissues is well described, the cellular mechanical environments, are organized around similar architecture of these tissues and its relationship to tissue architectural principles. function has only recently become the focus of study. It The purpose of this rev i ew is to highlight recent n ow appears that tensile-bearing dense connective d evelopments in our understanding of the cellular tissues may be a specific class of connective tissues that architecture of dense soft connective tissues and to display a common cellular organization characterized by discuss their functional implications. It will become fusiform cells with cytoplasmic projections and ga p clear that a 3-dimensional cellular arrangement, a junctions. These cells with their cellular projections are “cellular matrix”, consisting of fusiform cells with organised into a complex 3-dimensional network leading cytoplasmic projections and gap junctions may define a to a phy s i c a l l y, chemically and electrically connected s p e c i fic class of hy p o c e l l u l a r, tensile-bearing, dense cellular matrix.
    [Show full text]
  • Comparative Multi-Scale Hierarchical Structure of the Tail, Plantaris, and Achilles Tendons in 2 the Rat 3 Andrea H
    bioRxiv preprint doi: https://doi.org/10.1101/396309; this version posted August 20, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Comparative Multi-scale Hierarchical Structure of the Tail, Plantaris, and Achilles Tendons in 2 the Rat 3 Andrea H. Lee, Dawn M. Elliott* 4 Department of Biomedical Engineering, University of Delaware 5 *Corresponding author. Tel.: +1 302 831 1295. E-mail address: [email protected] (D.M. Elliott). 6 7 Keyword: Tendon, Hierarchical Structure, Multi-scale, Imaging 8 9 10 Abstract (500 words) 11 Rodent tendons are widely used to study human pathology, such as tendinopathy and 12 repair, and to address fundamental physiological questions about development, growth, and 13 remodeling. However, how the gross morphology and the multi-scale hierarchical structure of 14 rat tendons, such as the tail, plantaris, and Achillles tendons, compare to that of human 15 tendons are unknown. In addition, there remains disagreement about terminology and 16 definitions. Specifically, the definition of fascicle and fiber are often dependent on the diameter 17 size and not their characteristic features, which impairs the ability to compare across species 18 where the size of the fiber and fascicle might change with animal size and tendon function. 19 Thus, the objective of the study was to select a single species that is widely used for tendon 20 research (rat) and tendons with varying mechanical functions (tail, plantaris, Achilles) to 21 evaluate the hierarchical structure at multiple length scales.
    [Show full text]
  • Establishment and Investigation of Tendon-Derived Cell Lines Immortalized by the Human Telomerase Reverse Transcriptase Gene
    Aus der Chirurgischen Klinik und Poliklinik – Innenstadt, der Ludwig-Maximilians-Universität München Direktor: Prof. Dr. med. Wolf Mutschler Establishment and investigation of tendon- derived cell lines immortalized by the human telomerase reverse transcriptase gene. DISSERTATION zum Erwerb des Doktorgrades der Medizin an der Medizinischen Fakultät der Ludwig-Maximilians-Universität zu München vorgelegt von: Sophia Amina Poppe aus München, im Jahr 2010 Mit Genehmigung der Medizinischen Fakultät der Universität München Berichterstatter: Prof. Dr. med. Matthias Schieker Mitberichterstatter: Prof. Dr. Günther Eißner Prof. Dr. Peter Müller Mitbetreuung durch die promovierten Mitarbeiter: Dr. rer. nat. Denitsa Docheva Dekan: Prof. Dr. med. Dr. h.c. M. Reiser FACR, FRCR Tag der mündlichen Prüfung: 08. Juli 2010 1. INTRODUCTION......................................................................................................................... 4 1.1. General background......................................................................................................... 4 1.1.1. Anatomical and molecular structure of tendons.............................................. 4 1.1.1.1. Tendinous tissue................................................................................................ 4 1.1.1.2. Osteotendinous junction - enthesis............................................................ 5 1.1.1.3. Myotendinous junction................................................................................... 7 1.1.2. Development of tendons......................................................................................
    [Show full text]
  • Biomaterials in Tendon and Skeletal Muscle Tissue Engineering: Current Trends and Challenges
    materials Review Biomaterials in Tendon and Skeletal Muscle Tissue Engineering: Current Trends and Challenges Megane Beldjilali-Labro 1,†, Alejandro Garcia Garcia 1,†, Firas Farhat 1,† ID , Fahmi Bedoui 2, Jean-François Grosset 1, Murielle Dufresne 1 and Cécile Legallais 1,* ID 1 CNRS, UMR 7338, Biomécanique-Bioingénierie, Sorbonne Universités, Université de Technologie de Compiègne, 60200 Compiègne, France; [email protected] (M.B.-L.); [email protected] (A.G.G.); fi[email protected] (F.F.); [email protected] (J.-F.G.); [email protected] (M.D.) 2 CNRS FRE 2012, Laboratoire Roberval, Sorbonne Universités, Université de Technologie de Compiègne, 60200 Compiègne, France; [email protected] * Correspondence: [email protected] † These authors contributed equally to this work. Received: 31 May 2018; Accepted: 25 June 2018; Published: 29 June 2018 Abstract: Tissue engineering is a promising approach to repair tendon and muscle when natural healing fails. Biohybrid constructs obtained after cells’ seeding and culture in dedicated scaffolds have indeed been considered as relevant tools for mimicking native tissue, leading to a better integration in vivo. They can also be employed to perform advanced in vitro studies to model the cell differentiation or regeneration processes. In this review, we report and analyze the different solutions proposed in literature, for the reconstruction of tendon, muscle, and the myotendinous junction. They classically rely on the three pillars of tissue engineering, i.e., cells, biomaterials and environment (both chemical and physical stimuli). We have chosen to present biomimetic or bioinspired strategies based on understanding of the native tissue structure/functions/properties of the tissue of interest.
    [Show full text]
  • Nomina Histologica Veterinaria, First Edition
    NOMINA HISTOLOGICA VETERINARIA Submitted by the International Committee on Veterinary Histological Nomenclature (ICVHN) to the World Association of Veterinary Anatomists Published on the website of the World Association of Veterinary Anatomists www.wava-amav.org 2017 CONTENTS Introduction i Principles of term construction in N.H.V. iii Cytologia – Cytology 1 Textus epithelialis – Epithelial tissue 10 Textus connectivus – Connective tissue 13 Sanguis et Lympha – Blood and Lymph 17 Textus muscularis – Muscle tissue 19 Textus nervosus – Nerve tissue 20 Splanchnologia – Viscera 23 Systema digestorium – Digestive system 24 Systema respiratorium – Respiratory system 32 Systema urinarium – Urinary system 35 Organa genitalia masculina – Male genital system 38 Organa genitalia feminina – Female genital system 42 Systema endocrinum – Endocrine system 45 Systema cardiovasculare et lymphaticum [Angiologia] – Cardiovascular and lymphatic system 47 Systema nervosum – Nervous system 52 Receptores sensorii et Organa sensuum – Sensory receptors and Sense organs 58 Integumentum – Integument 64 INTRODUCTION The preparations leading to the publication of the present first edition of the Nomina Histologica Veterinaria has a long history spanning more than 50 years. Under the auspices of the World Association of Veterinary Anatomists (W.A.V.A.), the International Committee on Veterinary Anatomical Nomenclature (I.C.V.A.N.) appointed in Giessen, 1965, a Subcommittee on Histology and Embryology which started a working relation with the Subcommittee on Histology of the former International Anatomical Nomenclature Committee. In Mexico City, 1971, this Subcommittee presented a document entitled Nomina Histologica Veterinaria: A Working Draft as a basis for the continued work of the newly-appointed Subcommittee on Histological Nomenclature. This resulted in the editing of the Nomina Histologica Veterinaria: A Working Draft II (Toulouse, 1974), followed by preparations for publication of a Nomina Histologica Veterinaria.
    [Show full text]
  • Rebuilding Tendons: a Concise Review on the Potential of Dermal Fibroblasts
    cells Review Rebuilding Tendons: A Concise Review on the Potential of Dermal Fibroblasts Jin Chu 1 , Ming Lu 2, Christian G. Pfeifer 1,3 , Volker Alt 1,3 and Denitsa Docheva 1,* 1 Laboratory for Experimental Trauma Surgery, Department of Trauma Surgery, University Regensburg Medical Centre, 93053 Regensburg, Germany; [email protected] (J.C.); [email protected] (C.G.P.); [email protected] (V.A.) 2 Department of Orthopaedic Surgery, First Affiliated Hospital of Dalian Medical University, Dalian 116023, China; [email protected] 3 Department of Trauma Surgery, University Regensburg Medical Centre, 93053 Regensburg, Germany * Correspondence: [email protected]; Tel.: +49-(0)941-943-1605 Received: 29 June 2020; Accepted: 2 September 2020; Published: 8 September 2020 Abstract: Tendons are vital to joint movement by connecting muscles to bones. Along with an increasing incidence of tendon injuries, tendon disorders can burden the quality of life of patients or the career of athletes. Current treatments involve surgical reconstruction and conservative therapy. Especially in the elderly population, tendon recovery requires lengthy periods and it may result in unsatisfactory outcome. Cell-mediated tendon engineering is a rapidly progressing experimental and pre-clinical field, which holds great potential for an alternative approach to established medical treatments. The selection of an appropriate cell source is critical and remains under investigation. Dermal fibroblasts exhibit multiple similarities to tendon cells, suggesting they may be a promising cell source for tendon engineering. Hence, the purpose of this review article was in brief, to compare tendon to dermis tissues, and summarize in vitro studies on tenogenic differentiation of dermal fibroblasts.
    [Show full text]
  • Tendon Extracellular Matrix Remodeling and Defective Cell Polarization in the Presence of Collagen VI Mutations
    cells Article Tendon Extracellular Matrix Remodeling and Defective Cell Polarization in the Presence of Collagen VI Mutations Manuela Antoniel 1,2, Francesco Traina 3,4, Luciano Merlini 5 , Davide Andrenacci 1,2, Domenico Tigani 6, Spartaco Santi 1,2, Vittoria Cenni 1,2, Patrizia Sabatelli 1,2,*, Cesare Faldini 7 and Stefano Squarzoni 1,2 1 CNR-Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”-Unit of Bologna, 40136 Bologna, Italy; [email protected] (M.A.); [email protected] (D.A.); [email protected] (S.S.); [email protected] (V.C.); [email protected] (S.S.) 2 IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy 3 Ortopedia-Traumatologia e Chirurgia Protesica e dei Reimpianti d’Anca e di Ginocchio, Istituto Ortopedico Rizzoli di Bologna, 40136 Bologna, Italy; [email protected] 4 Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali, Università Degli Studi Di Messina, 98122 Messina, Italy 5 Department of Biomedical and Neuromotor Sciences, University of Bologna, 40123 Bologna, Italy; [email protected] 6 Department of Orthopedic and Trauma Surgery, Ospedale Maggiore, 40133 Bologna, Italy; [email protected] 7 1st Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-051-6366755; Fax: +39-051-4689922 Received: 20 December 2019; Accepted: 7 February 2020; Published: 11 February 2020 Abstract: Mutations in collagen VI genes cause two major clinical myopathies, Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), and the rarer myosclerosis myopathy. In addition to congenital muscle weakness, patients affected by collagen VI-related myopathies show axial and proximal joint contractures, and distal joint hypermobility, which suggest the involvement of tendon function.
    [Show full text]
  • Estudo Histológico E Biomecânico Da Tendinopatia Induzida Por Injeções Seriadas De Colagenase: Novo Modelo Experimental No
    CÉSAR DE CÉSAR NETTO Estudo histológico e biomecânico da tendinopatia induzida por injeções seriadas de colagenase: novo modelo experimental no tendão do calcâneo de coelhos Tese apresentada à Faculdade de Medicina da Universidade de São Paulo para obtenção do Título de Doutor em Ciências Programa de Ortopedia e Traumatologia Orientador: Prof. Dr. Túlio Diniz Fernandes São Paulo 2017 Dados Internacionais de Catalogação na Publicação (CIP) Preparada pela Biblioteca da Faculdade de Medicina da Universidade de São Paulo reprodução autorizada pelo autor Cesar Netto, Cesar de Estudo histológico e biomecânico da tendinopatia induzida por injeções seriadas de colagenase : novo modelo experimental no tendão do calcâneo de coelhos/ Cesar de Cesar Netto. -- São Paulo, 2017. Tese(doutorado)--Faculdade de Medicina da Universidade de São Paulo. Programa de Ortopedia e Traumatologia. Orientador: Túlio Diniz Fernandes. Descritores: 1.Tendinopatia 2.Tendão do calcâneo 3.Modelos animais 4.Tendinopatia induzida quimicamente 5.Colagenase bacteriana 6.Coelhos USP/FM/DBD-105/17 Dedicatória Dedicatória À minha amada esposa Sabrina, amor da minha vida, que sempre esteve ao meu lado, me apoiando nos momentos mais difíceis. À minha filha Manuela, razão do meu viver. À minha filha Juliana, que logo estará conosco e nos trará ainda mais alegria. Aos meus amados pais Luiz Edmundo e Maria Amélia, pelo amor e carinho, e por proporcionarem todas as oportunidades da minha vida. À minha querida irmã Marcela, eterna companheira, que me presenteou com meus amados sobrinhos Gianluca e Sofia. Ao meu saudoso avô Osvaldo, melhor amigo. A Deus, por me dar saúde e sempre me guiar pelos melhores caminhos.
    [Show full text]
  • Inhibition of ERK 1/2 Kinases Prevents Tendon Matrix Breakdown Ulrich Blache1,2,3, Stefania L
    www.nature.com/scientificreports OPEN Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown Ulrich Blache1,2,3, Stefania L. Wunderli1,2,3, Amro A. Hussien1,2, Tino Stauber1,2, Gabriel Flückiger1,2, Maja Bollhalder1,2, Barbara Niederöst1,2, Sandro F. Fucentese1 & Jess G. Snedeker1,2* Tendon extracellular matrix (ECM) mechanical unloading results in tissue degradation and breakdown, with niche-dependent cellular stress directing proteolytic degradation of tendon. Here, we show that the extracellular-signal regulated kinase (ERK) pathway is central in tendon degradation of load-deprived tissue explants. We show that ERK 1/2 are highly phosphorylated in mechanically unloaded tendon fascicles in a vascular niche-dependent manner. Pharmacological inhibition of ERK 1/2 abolishes the induction of ECM catabolic gene expression (MMPs) and fully prevents loss of mechanical properties. Moreover, ERK 1/2 inhibition in unloaded tendon fascicles suppresses features of pathological tissue remodeling such as collagen type 3 matrix switch and the induction of the pro-fbrotic cytokine interleukin 11. This work demonstrates ERK signaling as a central checkpoint to trigger tendon matrix degradation and remodeling using load-deprived tissue explants. Tendon is a musculoskeletal tissue that transmits muscle force to bone. To accomplish its biomechanical function, tendon tissues adopt a specialized extracellular matrix (ECM) structure1. Te load-bearing tendon compart- ment consists of highly aligned collagen-rich fascicles that are interspersed with tendon stromal cells. Tendon is a mechanosensitive tissue whereby physiological mechanical loading is vital for maintaining tendon archi- tecture and homeostasis2. Mechanical unloading of the tissue, for instance following tendon rupture or more localized micro trauma, leads to proteolytic breakdown of the tissue with severe deterioration of both structural and mechanical properties3–5.
    [Show full text]
  • Tendon Tissue Engineering
    C H A P T E R 3 Tendon Tissue Engineering K. Hampson*, N.R. Forsyth, A. El Haj and N. Maffulli Summary he successful healing of tendon injuries depends on numerous factors, including anatomical location, vascularity, skeletal maturity and the amount of tissue loss. Although spontaneous healing can T occur, this often results in the formation of scar tissue which is morphologically, biochemically and biomechanically different from healthy tendon tissue. This ultimately affects the functionality of the repaired tissue. Tendon tissue engineering aims to induce self-regeneration of the tendon tissue in vivo, or to produce a functional tissue replacement in vitro which can then be implanted into the body. The production of tendon tissue which is both viable and functional requires the generation of a uniaxially orientated matrix. The production and orientation of this matrix can potentially be altered by both biochemical and physical factors, and the combination of these two factors in a dose and time-dependent manner is potentially the key to successfully engineered tendons. This chapter reviews current strategies for tendon tissue engineering and the future challenges associated with this field. KEYWORDS: Scaffolds, Cell source, Mechanical stimuli, Growth factors, Gene therapy, Tissue engineering *Correspondence to: K. Hampson, ISTM, Keele University, Staffordshire, UK. E-mail: [email protected] Topics in Tissue Engineering, Vol. 4. Eds. N Ashammakhi, R Reis, & F Chiellini © 2008. Hampson et al. Tendon Tissue Engineering INTRODUCTION In the UK the National Health Service (NHS) treats thousands of damaged tendons each year, ranging from repetitive strain injuries (RSIs) to complete ruptures.
    [Show full text]
  • In Vitro Innovation of Tendon Tissue Engineering Strategies
    International Journal of Molecular Sciences Review In Vitro Innovation of Tendon Tissue Engineering Strategies 1, , 2, 1 Maria Rita Citeroni * y, Maria Camilla Ciardulli y, Valentina Russo , Giovanna Della Porta 2,3 , Annunziata Mauro 1 , Mohammad El Khatib 1 , Miriam Di Mattia 1 , Devis Galesso 4 , Carlo Barbera 4, Nicholas R. Forsyth 5 , Nicola Maffulli 2,6,7,8 and Barbara Barboni 1 1 Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; [email protected] (V.R.); [email protected] (A.M.); [email protected] (M.E.K.); [email protected] (M.D.M.); [email protected] (B.B.) 2 Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende, 84081 Baronissi (SA), Italy; [email protected] (M.C.C.); [email protected] (G.D.P.); n.maff[email protected] (N.M.) 3 Interdepartment Centre BIONAM, Università di Salerno, via Giovanni Paolo I, 84084 Fisciano (SA), Italy 4 Fidia Farmaceutici S.p.A., via Ponte della Fabbrica 3/A, 35031 Abano Terme (PD), Italy; DGalesso@fidiapharma.it (D.G.); CBarbera@fidiapharma.it (C.B.) 5 Guy Hilton Research Centre, School of Pharmacy and Bioengineering, Keele University, Thornburrow Drive, Stoke on Trent ST4 7QB, UK; [email protected] 6 Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, Via San Leonardo 1, 84131 Salerno, Italy 7 Centre for Sports and Exercise Medicine, Barts and The London School of Medicine and Dentistry, Mile End Hospital, Queen Mary University of London, 275 Bancroft Road, London E1 4DG, UK 8 School of Pharmacy and Bioengineering, Keele University School of Medicine, Thornburrow Drive, Stoke on Trent ST5 5BG, UK * Correspondence: [email protected]; Tel.: +39-(347)-940-0970 These authors contributed equally to this review.
    [Show full text]