Skip to main content
SpringerLink
Log in
Book cover

Cell Engineering and Regeneration pp 1–31Cite as

Biological Augmentation for Tendon Repair: Lessons to be Learned from Development, Disease, and Tendon Stem Cell Research

  • Living reference work entry
  • First Online:

Part of the book series: Reference Series in Biomedical Engineering ((TIENRE))

Abstract

Tendons resemble connective tissues rich in highly organized collagen fibers, displaying a remarkably high tensile strength. However, partly due to the low number of tissue-resident cells and their more or less avascular nature, tendons heal relatively slowly. As there is a growing socio-economic need for effective and reproducible treatments to repair injured tendons, researchers and clinicians are challenged to develop strategies to restore native tendon structure and functionality.

This chapter highlights the features and functions of tendon-resident cells and their niche, beginning with a general view on tendon structure. It further gives an overview of tendon development and the cellular and molecular events underlying tendon aging. Finally, we will close the chapter by briefly outlining current strategies to augment tendon repair, aiming at reaching the ambitious goal of functional tendon regeneration.

This is a preview of subscription content, log in via an institution.

References

  • Abate M, Silbernagel KG, Siljeholm C, Di Iorio A, De Amicis D, Salini V, Werner S, Paganelli R (2009) Pathogenesis of tendinopathies: inflammation or degeneration? Arthritis Res Ther 11:235

    Article  Google Scholar 

  • Ahmed M, Ffrench-Constant C (2016) Extracellular matrix regulation of stem cell behavior. Curr Stem Cell Rep 2:197–206

    Article  Google Scholar 

  • Alberton P, Dex S, Popov C, Shukunami C, Schieker M, Docheva D (2015) Loss of tenomodulin results in reduced self-renewal and augmented senescence of tendon stem/progenitor cells. Stem Cells Dev 24:597–609

    Article  Google Scholar 

  • Almekinders LC, Deol G (1999) The effects of aging, antiinflammatory drugs, and ultrasound on the in vitro response of tendon tissue. Am J Sports Med 27:417–421

    Article  Google Scholar 

  • Ameye L, Aria D, Jepsen K, Oldberg A, Xu T, Young MF (2002) Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis. FASEB J 16:673–680

    Article  Google Scholar 

  • Ansorge HL, Meng X, Zhang G, Veit G, Sun M, Klement JF, Beason DP, Soslowsky LJ, Koch M, Birk DE (2009) Type XIV collagen regulates Fibrillogenesis: PREMATURE COLLAGEN FIBRIL GROWTH AND TISSUE DYSFUNCTION IN NULL MICE. J Biol Chem 284:8427–8438

    Article  Google Scholar 

  • Arampatzis A, Karamanidis K, Morey-Klapsing G, De Monte G, Stafilidis S (2007) Mechanical properties of the triceps surae tendon and aponeurosis in relation to intensity of sport activity. J Biomech 40:1946–1952

    Article  Google Scholar 

  • Bailey AJ (2001) Molecular mechanisms of ageing in connective tissues. Mech Ageing Dev 122:735–755

    Article  Google Scholar 

  • Banes AJ, Donlon K, Link GW, Gillespie Y, Bevin AG, Peterson HD, Bynum D, Watts S, Dahners L (1988) Cell populations of tendon: a simplified method for isolation of synovial cells and internal fibroblasts: confirmation of origin and biologic properties. J Orthop Res 6:83–94

    Article  Google Scholar 

  • Bank RA, TeKoppele JM, Oostingh G, Hazleman BL, Riley GP (1999) Lysylhydroxylation and non-reducible crosslinking of human supraspinatus tendon collagen: changes with age and in chronic rotator cuff tendinitis. Ann Rheum Dis 58:35–41

    Article  Google Scholar 

  • Benjamin M, Ralphs JR (1997) Tendons and ligaments – an overview. Histol Histopathol 12:1135–1144

    Google Scholar 

  • Benjamin M, Kaiser E, Milz S (2008) Structure-function relationships in tendons: a review. J Anat 212:211–228

    Article  Google Scholar 

  • Berenson MC, Blevins FT, Plaas AH, Vogel KG (1996) Proteoglycans of human rotator cuff tendons. J Orthop Res 14:518–525

    Article  Google Scholar 

  • Bi Y, Ehirchiou D, Kilts TM, Inkson CA, Embree MC, Sonoyama W, Li L, Leet AI, Seo BM, Zhang L, Shi S, Young MF (2007) Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nat Med 13:1219–1227

    Article  Google Scholar 

  • Birch HL, Bailey JV, Bailey AJ, Goodship AE (1999) Age-related changes to the molecular and cellular components of equine flexor tendons. Equine Vet J 31:391–396

    Article  Google Scholar 

  • Birch HL, Peffers MJ, Clegg PD (2016) Influence of ageing on tendon homeostasis. Adv Exp Med Biol 920:247–260

    Article  Google Scholar 

  • Blitz E, Sharir A, Akiyama H, Zelzer E (2013) Tendon-bone attachment unit is formed modularly by a distinct pool of Scx- and Sox9-positive progenitors. Development 140:2680–2690

    Article  Google Scholar 

  • Brent AE, Schweitzer R, Tabin CJ (2003) A somitic compartment of tendon progenitors. Cell 113:235–248

    Article  Google Scholar 

  • Brent AE, Braun T, Tabin CJ (2005) Genetic analysis of interactions between the somitic muscle, cartilage and tendon cell lineages during mouse development. Development 132:515–528

    Article  Google Scholar 

  • Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L (2010) Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int 78:838–848

    Article  Google Scholar 

  • Canty EG, Kadler KE (2002) Collagen fibril biosynthesis in tendon: a review and recent insights. Comp Biochem Physiol A Mol Integr Physiol 133:979–985

    Article  Google Scholar 

  • Canty EG, Kadler KE (2005) Procollagen trafficking, processing and fibrillogenesis. J Cell Sci 118:1341–1353

    Article  Google Scholar 

  • Caplan AI (2008) All MSCs are pericytes? Cell Stem Cell 3:229–230

    Article  Google Scholar 

  • Cardwell RD, Dahlgren LA, Goldstein AS (2014) Electrospun fibre diameter, not alignment, affects mesenchymal stem cell differentiation into the tendon/ligament lineage. J Tissue Eng Regen Med 8:937–945

    Article  Google Scholar 

  • Carvalho HF, Felisbino SL, Covizi DZ, Della Colleta HH, Gomes L (2000) Structure and proteoglycan composition of specialized regions of the elastic tendon of the chicken wing. Cell Tissue Res 300:435–446

    Article  Google Scholar 

  • Chakravarti S (2002) Functions of lumican and fibromodulin: lessons from knockout mice. Glycoconj J 19:287–293

    Article  Google Scholar 

  • Chen JW, Galloway JL (2014) The development of zebrafish tendon and ligament progenitors. Development 141:2035–2045

    Article  Google Scholar 

  • Chen JM, Willers C, Xu J, Wang A, Zheng MH (2007) Autologous tenocyte therapy using porcine-derived bioscaffolds for massive rotator cuff defect in rabbits. Tissue Eng 13:1479–1491

    Article  Google Scholar 

  • Chen J, Yu Q, Wu B, Lin Z, Pavlos NJ, Xu J, Ouyang H, Wang A, Zheng MH (2011) Autologous tenocyte therapy for experimental Achilles tendinopathy in a rabbit model. Tissue Eng Part A 17:2037–2048

    Article  Google Scholar 

  • Chuang HN, Cheng HY, Hsiao KM, Lin CW, Lin ML, Pan H (2010) The zebrafish homeobox gene irxl1 is required for brain and pharyngeal arch morphogenesis. Dev Dyn 239:639–650

    Article  Google Scholar 

  • Chuen FS, Chuk CY, Ping WY, Nar WW, Kim HL, Ming CK (2004) Immunohistochemical characterization of cells in adult human patellar tendons. J Histochem Cytochem 52:1151–1157

    Article  Google Scholar 

  • Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, Norotte C, Teng PN, Traas J, Schugar R, Deasy BM, Badylak S, Buhring HJ, Giacobino JP, Lazzari L, Huard J, Peault B (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3:301–313

    Article  Google Scholar 

  • Dakin SG, Dudhia J, Werling NJ, Werling D, Abayasekara DR, Smith RK (2012) Inflamm-aging and arachadonic acid metabolite differences with stage of tendon disease. PLoS One 7:e48978

    Article  Google Scholar 

  • Dakin SG, Martinez FO, Yapp C, Wells G, Oppermann U, Dean BJ, Smith RD, Wheway K, Watkins B, Roche L, Carr AJ (2015) Inflammation activation and resolution in human tendon disease. Sci Transl Med 7:311ra173

    Article  Google Scholar 

  • Das RK, Zouani OF (2014) A review of the effects of the cell environment physicochemical nanoarchitecture on stem cell commitment. Biomaterials 35:5278–5293

    Article  Google Scholar 

  • Davidson CJ, Ganion LR, Gehlsen GM, Verhoestra B, Roepke JE, Sevier TL (1997) Rat tendon morphologic and functional changes resulting from soft tissue mobilization. Med Sci Sports Exerc 29:313–319

    Article  Google Scholar 

  • de Souza LE, Malta TM, Kashima Haddad S, Covas DT (2016) Mesenchymal stem cells and Pericytes: to what extent are they related? Stem Cells Dev 25:1843

    Article  Google Scholar 

  • De Vilder EY, Vanakker OM (2015) From variome to phenome: pathogenesis, diagnosis and management of ectopic mineralization disorders. World J Clin Cases 3:556–574

    Article  Google Scholar 

  • Dean BJ, Gettings P, Dakin SG, Carr AJ (2016) Are inflammatory cells increased in painful human tendinopathy? A systematic review. Br J Sports Med 50:216–220

    Article  Google Scholar 

  • Deries M, Thorsteinsdottir S (2016) Axial and limb muscle development: dialogue with the neighbourhood. Cell Mol Life Sci 73:4415–4431

    Article  Google Scholar 

  • Dex S, Lin D, Shukunami C, Docheva D (2016) Tenogenic modulating insider factor: systematic assessment on the functions of tenomodulin gene. Gene 587:1–17

    Article  Google Scholar 

  • Docheva D, Hunziker EB, Fassler R, Brandau O (2005) Tenomodulin is necessary for tenocyte proliferation and tendon maturation. Mol Cell Biol 25:699–705

    Article  Google Scholar 

  • Docheva D, Muller SA, Majewski M, Evans CH (2015) Biologics for tendon repair. Adv Drug Deliv Rev 84:222–239

    Article  Google Scholar 

  • Dudhia J, Scott CM, Draper ER, Heinegard D, Pitsillides AA, Smith RK (2007) Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity. Aging Cell 6:547–556

    Article  Google Scholar 

  • Dunkman AA, Buckley MR, Mienaltowski MJ, Adams SM, Thomas SJ, Satchell L, Kumar A, Pathmanathan L, Beason DP, Iozzo RV, Birk DE, Soslowsky LJ (2013) Decorin expression is important for age-related changes in tendon structure and mechanical properties. Matrix Biol 32:3–13

    Article  Google Scholar 

  • Dunkman AA, Buckley MR, Mienaltowski MJ, Adams SM, Thomas SJ, Kumar A, Beason DP, Iozzo RV, Birk DE, Soslowsky LJ (2014) The injury response of aged tendons in the absence of biglycan and decorin. Matrix Biol 35:232–238

    Article  Google Scholar 

  • Dyment NA, Liu CF, Kazemi N, Aschbacher-Smith LE, Kenter K, Breidenbach AP, Shearn JT, Wylie C, Rowe DW, Butler DL (2013) The paratenon contributes to scleraxis-expressing cells during patellar tendon healing. PLoS One 8:e59944

    Article  Google Scholar 

  • Flahiff CM, Brooks AT, Hollis JM, Vander Schilden JL, Nicholas RW (1995) Biomechanical analysis of patellar tendon allografts as a function of donor age. Am J Sports Med 23:354–358

    Article  Google Scholar 

  • Floridi A, Ippolito E, Postacchini F (1981) Age-related changes in the metabolism of tendon cells. Connect Tissue Res 9:95–97

    Article  Google Scholar 

  • Frommer G, Vorbruggen G, Pasca G, Jackle H, Volk T (1996) Epidermal egr-like zinc finger protein of drosophila participates in myotube guidance. EMBO J 15:1642–1649

    Google Scholar 

  • Gaspar D, Spanoudes K, Holladay C, Pandit A, Zeugolis D (2015) Progress in cell-based therapies for tendon repair. Adv Drug Deliv Rev 84:240–256

    Article  Google Scholar 

  • Gaut L, Duprez D (2016) Tendon development and diseases. Wiley Interdiscip Rev Dev Biol 5:5–23

    Article  Google Scholar 

  • Gautieri A, Passini FS, Silvan U, Guizar-Sicairos M, Carimati G, Volpi P, Moretti M, Schoenhuber H, Redaelli A, Berli M, Snedeker JG (2016) Advanced glycation end-products: mechanics of aged collagen from molecule to tissue. Matrix Biol. https://doi.org/10.1016/j.matbio.2016.09.001

  • Gehwolf R, Wagner A, Lehner C, Bradshaw AD, Scharler C, Niestrawska JA, Holzapfel GA, Bauer HC, Tempfer H, Traweger A (2016) Pleiotropic roles of the matricellular protein Sparc in tendon maturation and ageing. Sci Rep 6:32635

    Article  Google Scholar 

  • Goh KL, Holmes DF, Lu HY, Richardson S, Kadler KE, Purslow PP, Wess TJ (2008) Ageing changes in the tensile properties of tendons: influence of collagen fibril volume fraction. J Biomech Eng 130:021011

    Article  Google Scholar 

  • Goh KL, Holmes DF, Lu Y, Purslow PP, Kadler KE, Bechet D, Wess TJ (2012) Bimodal collagen fibril diameter distributions direct age-related variations in tendon resilience and resistance to rupture. J Appl Physiol (1985) 113:878–888

    Article  Google Scholar 

  • Gordon JA, Freedman BR, Zuskov A, Iozzo RV, Birk DE, Soslowsky LJ (2015) Achilles tendons from decorin- and biglycan-null mouse models have inferior mechanical and structural properties predicted by an image-based empirical damage model. J Biomech 48:2110–2115

    Article  Google Scholar 

  • Grases F, Muntaner-Gimbernat L, Vilchez-Mira M, Costa-Bauza A, Tur F, Prieto RM, Torrens-Mas M, Vega FG (2015) Characterization of deposits in patients with calcific tendinopathy of the supraspinatus. Role of phytate and osteopontin. J Orthop Res 33:475–482

    Article  Google Scholar 

  • Grenier J, Teillet MA, Grifone R, Kelly RG, Duprez D (2009) Relationship between neural crest cells and cranial mesoderm during head muscle development. PLoS One 4:e4381

    Article  Google Scholar 

  • Guerquin MJ, Charvet B, Nourissat G, Havis E, Ronsin O, Bonnin MA, Ruggiu M, Olivera-Martinez I, Robert N, Lu Y, Kadler KE, Baumberger T, Doursounian L, Berenbaum F, Duprez D (2013) Transcription factor EGR1 directs tendon differentiation and promotes tendon repair. J Clin Invest 123:3564–3576

    Article  Google Scholar 

  • Hankemeier S, Keus M, Zeichen J, Jagodzinski M, Barkhausen T, Bosch U, Krettek C, Van Griensven M (2005) Modulation of proliferation and differentiation of human bone marrow stromal cells by fibroblast growth factor 2: potential implications for tissue engineering of tendons and ligaments. Tissue Eng 11:41–49

    Article  Google Scholar 

  • Harris MT, Butler DL, Boivin GP, Florer JB, Schantz EJ, Wenstrup RJ (2004) Mesenchymal stem cells used for rabbit tendon repair can form ectopic bone and express alkaline phosphatase activity in constructs. J Orthop Res 22:998–1003

    Article  Google Scholar 

  • Havis E, Bonnin MA, Esteves de Lima J, Charvet B, Milet C, Duprez D (2016) TGFbeta and FGF promote tendon progenitor fate and act downstream of muscle contraction to regulate tendon differentiation during chick limb development. Development 143:3839–3851

    Article  Google Scholar 

  • Heinemeier KM, Schjerling P, Heinemeier J, Magnusson SP, Kjaer M (2013) Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb (14)C. FASEB J 27:2074–2079

    Article  Google Scholar 

  • Helm GA, Li JZ, Alden TD, Hudson SB, Beres EJ, Cunningham M, Mikkelsen MM, Pittman DD, Kerns KM, Kallmes DF (2001) A light and electron microscopic study of ectopic tendon and ligament formation induced by bone morphogenetic protein-13 adenoviral gene therapy. J Neurosurg 95:298–307

    Article  Google Scholar 

  • Hilfiker A, Kasper C, Hass R, Haverich A (2011) Mesenchymal stem cells and progenitor cells in connective tissue engineering and regenerative medicine: is there a future for transplantation? Langenbecks Arch Surg 396:489–497

    Article  Google Scholar 

  • Holladay C, Abbah SA, O’Dowd C, Pandit A, Zeugolis DI (2016) Preferential tendon stem cell response to growth factor supplementation. J Tissue Eng Regen Med 10:783–798

    Article  Google Scholar 

  • Holzwarth C, Vaegler M, Gieseke F, Pfister SM, Handgretinger R, Kerst G, Muller I (2010) Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells. BMC Cell Biol 11:11

    Article  Google Scholar 

  • Humbert F, Montesano R, Perrelet A, Orci L (1976) Junctions in developing human and rat kidney: a freeze-fracture study. J Ultrastruct Res 56:202–214

    Article  Google Scholar 

  • Ippolito E, Natali PG, Postacchini F, Accinni L, De Martino C (1980) Morphological, immunochemical, and biochemical study of rabbit achilles tendon at various ages. J Bone Joint Surg Am 62:583–598

    Article  Google Scholar 

  • Ito Y, Toriuchi N, Yoshitaka T, Ueno-Kudoh H, Sato T, Yokoyama S, Nishida K, Akimoto T, Takahashi M, Miyaki S, Asahara H (2010) The Mohawk homeobox gene is a critical regulator of tendon differentiation. Proc Natl Acad Sci U S A 107:10538–10542

    Article  Google Scholar 

  • Kadler KE, Hojima Y, Prockop DJ (1990) Collagen fibrils in vitro grow from pointed tips in the C- to N-terminal direction. Biochem J 268:339–343

    Article  Google Scholar 

  • Kalamajski S, Liu C, Tillgren V, Rubin K, Oldberg A, Rai J, Weis M, Eyre DR (2014) Increased C-telopeptide cross-linking of tendon type I collagen in fibromodulin-deficient mice. J Biol Chem 289:18873–18879

    Article  Google Scholar 

  • Kannus P (2000) Structure of the tendon connective tissue. Scand J Med Sci Sports 10:312–320

    Article  Google Scholar 

  • Kannus P, Paavola M, Józsa L (2005) Aging and degeneration of tendons. Springer, London

    Book  Google Scholar 

  • Kardon G (1998) Muscle and tendon morphogenesis in the avian hind limb. Development 125:4019–4032

    Google Scholar 

  • Kielty CM, Sherratt MJ, Shuttleworth CA (2002) Elastic fibres. J Cell Sci 115:2817–2828

    Google Scholar 

  • Kietrys DM, Barr-Gillespie AE, Amin M, Wade CK, Popoff SN, Barbe MF (2012) Aging contributes to inflammation in upper extremity tendons and declines in forelimb agility in a rat model of upper extremity overuse. PLoS One 7:e46954

    Article  Google Scholar 

  • Kimura W, Machii M, Xue X, Sultana N, Hikosaka K, Sharkar MT, Uezato T, Matsuda M, Koseki H, Miura N (2011) Irxl1 mutant mice show reduced tendon differentiation and no patterning defects in musculoskeletal system development. Genesis 49:2–9

    Article  Google Scholar 

  • Kohler J, Popov C, Klotz B, Alberton P, Prall WC, Haasters F, Muller-Deubert S, Ebert R, Klein-Hitpass L, Jakob F, Schieker M, Docheva D (2013) Uncovering the cellular and molecular changes in tendon stem/progenitor cells attributed to tendon aging and degeneration. Aging Cell 12:988–999

    Article  Google Scholar 

  • Koskinen SO, Heinemeier KM, Olesen JL, Langberg H, Kjaer M (2004) Physical exercise can influence local levels of matrix metalloproteinases and their inhibitors in tendon-related connective tissue. J Appl Physiol (1985) 96:861–864

    Article  Google Scholar 

  • Kubo K, Morimoto M, Komuro T, Tsunoda N, Kanehisa H, Fukunaga T (2007) Age-related differences in the properties of the plantar flexor muscles and tendons. Med Sci Sports Exerc 39:541–547

    Article  Google Scholar 

  • Lee WY, Lui PP, Rui YF (2012) Hypoxia-mediated efficient expansion of human tendon-derived stem cells in vitro. Tissue Eng Part A 18:484–498

    Article  Google Scholar 

  • Lee CH, Lee FY, Tarafder S, Kao K, Jun Y, Yang G, Mao JJ (2015) Harnessing endogenous stem/progenitor cells for tendon regeneration. J Clin Invest 125:2690–2701

    Article  Google Scholar 

  • Legerlotz K, Dorn J, Richter J, Rausch M, Leupin O (2014) Age-dependent regulation of tendon crimp structure, cell length and gap width with strain. Acta Biomater 10:4447–4455

    Article  Google Scholar 

  • Lehner C, Gehwolf R, Ek JC, Korntner S, Bauer H, Bauer HC, Traweger A, Tempfer H (2016) The blood-tendon barrier: identification and characterisation of a novel tissue barrier in tendon blood vessels. Eur Cell Mater 31:296–311

    Article  Google Scholar 

  • Lejard V, Blais F, Guerquin MJ, Bonnet A, Bonnin MA, Havis E, Malbouyres M, Bidaud CB, Maro G, Gilardi-Hebenstreit P, Rossert J, Ruggiero F, Duprez D (2011) EGR1 and EGR2 involvement in vertebrate tendon differentiation. J Biol Chem 286:5855–5867

    Article  Google Scholar 

  • Lener T, Gimona M, Aigner L, Borger V, Buzas E, Camussi G, Chaput N, Chatterjee D, Court FA, Del Portillo HA, O’Driscoll L, Fais S, Falcon-Perez JM, Felderhoff-Mueser U, Fraile L, Gho YS, Gorgens A, Gupta RC, Hendrix A, Hermann DM, Hill AF, Hochberg F, Horn PA, de Kleijn D, Kordelas L, Kramer BW, Kramer-Albers EM, Laner-Plamberger S, Laitinen S, Leonardi T, Lorenowicz MJ, Lim SK, Lotvall J, Maguire CA, Marcilla A, Nazarenko I, Ochiya T, Patel T, Pedersen S, Pocsfalvi G, Pluchino S, Quesenberry P, Reischl IG, Rivera FJ, Sanzenbacher R, Schallmoser K, Slaper-Cortenbach I, Strunk D, Tonn T, Vader P, van Balkom BW, Wauben M, Andaloussi SE, Thery C, Rohde E, Giebel B (2015) Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper. J Extracell Vesicles 4:30087

    Article  Google Scholar 

  • Lewis G, Shaw KM (1997) Tensile properties of human tendo Achillis: effect of donor age and strain rate. J Foot Ankle Surg 36:435–445

    Article  Google Scholar 

  • Lomas AJ, Ryan CN, Sorushanova A, Shologu N, Sideri AI, Tsioli V, Fthenakis GC, Tzora A, Skoufos I, Quinlan LR, O’Laighin G, Mullen AM, Kelly JL, Kearns S, Biggs M, Pandit A, Zeugolis DI (2015) The past, present and future in scaffold-based tendon treatments. Adv Drug Deliv Rev 84:257–277

    Article  Google Scholar 

  • Longo UG, Ronga M, Maffulli N (2009) Achilles tendinopathy. Sports Med Arthrosc 17:112–126

    Article  Google Scholar 

  • Lui PP (2013) Identity of tendon stem cells – how much do we know? J Cell Mol Med 17:55–64

    Article  Google Scholar 

  • Lui PP (2015) Stem cell technology for tendon regeneration: current status, challenges, and future research directions. Stem Cells Cloning 8:163–174

    Google Scholar 

  • Lui PP, Chan KM (2011) Tendon-derived stem cells (TDSCs): from basic science to potential roles in tendon pathology and tissue engineering applications. Stem Cell Rev 7:883–897

    Article  Google Scholar 

  • Maeda T, Sakabe T, Sunaga A, Sakai K, Rivera AL, Keene DR, Sasaki T, Stavnezer E, Iannotti J, Schweitzer R, Ilic D, Baskaran H, Sakai T (2011) Conversion of mechanical force into TGF-beta-mediated biochemical signals. Curr Biol 21:933–941

    Article  Google Scholar 

  • Maffulli N, Khan KM, Puddu G (1998) Overuse tendon conditions: time to change a confusing terminology. Arthroscopy 14:840–843

    Article  Google Scholar 

  • Maffulli N, Wong J, Almekinders LC (2003) Types and epidemiology of tendinopathy. Clin Sports Med 22:675–692

    Article  Google Scholar 

  • Mazzocca AD, McCarthy MB, Chowaniec D, Cote MP, Judson CH, Apostolakos J, Solovyova O, Beitzel K, Arciero RA (2011) Bone marrow-derived mesenchymal stem cells obtained during arthroscopic rotator cuff repair surgery show potential for tendon cell differentiation after treatment with insulin. Arthroscopy 27:1459–1471

    Article  Google Scholar 

  • McNeilly CM, Banes AJ, Benjamin M, Ralphs JR (1996) Tendon cells in vivo form a three dimensional network of cell processes linked by gap junctions. J Anat 189(Pt 3):593–600

    Google Scholar 

  • Meller R, Schiborra F, Brandes G, Knobloch K, Tschernig T, Hankemeier S, Haasper C, Schmiedl A, Jagodzinski M, Krettek C, Willbold E (2009) Postnatal maturation of tendon, cruciate ligament, meniscus and articular cartilage: a histological study in sheep. Ann Anat 191:575–585

    Article  Google Scholar 

  • Mendias CL, Gumucio JP, Bakhurin KI, Lynch EB, Brooks SV (2012) Physiological loading of tendons induces scleraxis expression in epitenon fibroblasts. J Orthop Res 30:606–612

    Article  Google Scholar 

  • Mienaltowski MJ, Adams SM, Birk DE (2013) Regional differences in stem cell/progenitor cell populations from the mouse achilles tendon. Tissue Eng Part A 19:199–210

    Article  Google Scholar 

  • Morita W, Snelling SJ, Dakin SG, Carr AJ (2016) Profibrotic mediators in tendon disease: a systematic review. Arthritis Res Ther 18:269

    Article  Google Scholar 

  • Murchison ND, Price BA, Conner DA, Keene DR, Olson EN, Tabin CJ, Schweitzer R (2007) Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons. Development 134:2697–2708

    Article  Google Scholar 

  • Ni M, Rui YF, Tan Q, Liu Y, Xu LL, Chan KM, Wang Y, Li G (2013) Engineered scaffold-free tendon tissue produced by tendon-derived stem cells. Biomaterials 34:2024–2037

    Article  Google Scholar 

  • Nourissat G, Berenbaum F, Duprez D (2015) Tendon injury: from biology to tendon repair. Nat Rev Rheumatol 11:223–233

    Article  Google Scholar 

  • Oliva F, Via AG, Maffulli N (2011) Calcific tendinopathy of the rotator cuff tendons. Sports Med Arthrosc 19:237–243

    Article  Google Scholar 

  • Oliva F, Via AG, Maffulli N (2012) Physiopathology of intratendinous calcific deposition. BMC Med 10:95

    Article  Google Scholar 

  • Onambele GL, Narici MV, Maganaris CN (2006) Calf muscle-tendon properties and postural balance in old age. J Appl Physiol (1985) 100:2048–2056

    Article  Google Scholar 

  • Oryan A, Shoushtari AH (2008) Histology and ultrastructure of the developing superficial digital flexor tendon in rabbits. Anat Histol Embryol 37:134–140

    Article  Google Scholar 

  • Pajala A, Melkko J, Leppilahti J, Ohtonen P, Soini Y, Risteli J (2009) Tenascin-C and type I and III collagen expression in total Achilles tendon rupture. An immunohistochemical study. Histol Histopathol 24:1207–1211

    Google Scholar 

  • Park A, Hogan MV, Kesturu GS, James R, Balian G, Chhabra AB (2010) Adipose-derived mesenchymal stem cells treated with growth differentiation factor-5 express tendon-specific markers. Tissue Eng Part A 16:2941–2951

    Article  Google Scholar 

  • Peacock EE Jr (1959) A study of the circulation in normal tendons and healing grafts. Ann Surg 149:415–428

    Article  Google Scholar 

  • Pingel J, Lu Y, Starborg T, Fredberg U, Langberg H, Nedergaard A, Weis M, Eyre D, Kjaer M, Kadler KE (2014) 3-D ultrastructure and collagen composition of healthy and overloaded human tendon: evidence of tenocyte and matrix buckling. J Anat 224:548–555

    Article  Google Scholar 

  • Popov C, Burggraf M, Kreja L, Ignatius A, Schieker M, Docheva D (2015a) Mechanical stimulation of human tendon stem/progenitor cells results in upregulation of matrix proteins, integrins and MMPs, and activation of p38 and ERK1/2 kinases. BMC Mol Biol 16:6

    Article  Google Scholar 

  • Popov C, Kohler J, Docheva D (2015b) Activation of EphA4 and EphB2 reverse signaling restores the age-associated reduction of self-renewal, migration, and actin turnover in human tendon stem/progenitor cells. Front Aging Neurosci 7:246

    Article  Google Scholar 

  • Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak MZ (2006) Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia 20:1487–1495

    Article  Google Scholar 

  • Riley GP, Harrall RL, Constant CR, Chard MD, Cawston TE, Hazleman BL (1994) Glycosaminoglycans of human rotator cuff tendons: changes with age and in chronic rotator cuff tendinitis. Ann Rheum Dis 53:367–376

    Article  Google Scholar 

  • Riley GP, Curry V, DeGroot J, van El B, Verzijl N, Hazleman BL, Bank RA (2002) Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology. Matrix Biol 21:185–195

    Article  Google Scholar 

  • Robinson PS, Huang TF, Kazam E, Iozzo RV, Birk DE, Soslowsky LJ (2005) Influence of decorin and biglycan on mechanical properties of multiple tendons in knockout mice. J Biomech Eng 127:181–185

    Article  Google Scholar 

  • Rolf CG, Fu BS, Pau A, Wang W, Chan B (2001) Increased cell proliferation and associated expression of PDGFRbeta causing hypercellularity in patellar tendinosis. Rheumatology (Oxford) 40:256–261

    Article  Google Scholar 

  • Rui YF, Lui PP, Li G, Fu SC, Lee YW, Chan KM (2010) Isolation and characterization of multipotent rat tendon-derived stem cells. Tissue Eng Part A 16:1549–1558

    Article  Google Scholar 

  • Rui YF, Lui PP, Chan LS, Chan KM, Fu SC, Li G (2011) Does erroneous differentiation of tendon-derived stem cells contribute to the pathogenesis of calcifying tendinopathy? Chin Med J (Engl) 124:606–610

    Google Scholar 

  • Rui YF, Lui PP, Wong YM, Tan Q, Chan KM (2013a) Altered fate of tendon-derived stem cells isolated from a failed tendon-healing animal model of tendinopathy. Stem Cells Dev 22:1076–1085

    Article  Google Scholar 

  • Rui YF, Lui PP, Wong YM, Tan Q, Chan KM (2013b) BMP-2 stimulated non-tenogenic differentiation and promoted proteoglycan deposition of tendon-derived stem cells (TDSCs) in vitro. J Orthop Res 31:746–753

    Article  Google Scholar 

  • Runesson E, Ackermann P, Karlsson J, Eriksson BI (2015) Nucleostemin- and Oct 3/4-positive stem/progenitor cells exhibit disparate anatomical and temporal expression during rat Achilles tendon healing. BMC Musculoskelet Disord 16:212

    Article  Google Scholar 

  • Salingcarnboriboon R, Yoshitake H, Tsuji K, Obinata M, Amagasa T, Nifuji A, Noda M (2003) Establishment of tendon-derived cell lines exhibiting pluripotent mesenchymal stem cell-like property. Exp Cell Res 287:289–300

    Article  Google Scholar 

  • Sassoon AA, Ozasa Y, Chikenji T, Sun YL, Larson DR, Maas ML, Zhao C, Jen J, Amadio PC (2012) Skeletal muscle and bone marrow derived stromal cells: a comparison of tenocyte differentiation capabilities. J Orthop Res 30:1710–1718

    Article  Google Scholar 

  • Schiele NR, Marturano JE, Kuo CK (2013) Mechanical factors in embryonic tendon development: potential cues for stem cell tenogenesis. Curr Opin Biotechnol 24:834–840

    Article  Google Scholar 

  • Schwartz MA (2010) Integrins and extracellular matrix in mechanotransduction. Cold Spring Harb Perspect Biol 2:a005066

    Article  Google Scholar 

  • Schweitzer R, Chyung JH, Murtaugh LC, Brent AE, Rosen V, Olson EN, Lassar A, Tabin CJ (2001) Analysis of the tendon cell fate using Scleraxis, a specific marker for tendons and ligaments. Development 128:3855–3866

    Google Scholar 

  • Sharma P, Maffulli N (2006) Biology of tendon injury: healing, modeling and remodeling. J Musculoskelet Neuronal Interact 6:181–190

    Google Scholar 

  • Sharma RI, Snedeker JG (2012) Paracrine interactions between mesenchymal stem cells affect substrate driven differentiation toward tendon and bone phenotypes. PLoS One 7:e31504

    Article  Google Scholar 

  • Smith RK, Zunino L, Webbon PM, Heinegard D (1997) The distribution of cartilage oligomeric matrix protein (COMP) in tendon and its variation with tendon site, age and load. Matrix Biol 16:255–271

    Article  Google Scholar 

  • Snedeker JG, Gautieri A (2014) The role of collagen crosslinks in ageing and diabetes – the good, the bad, and the ugly. Muscles Ligaments Tendons J 4:303–308

    Google Scholar 

  • Speed C (2016) Inflammation in tendon disorders. Adv Exp Med Biol 920:209–220

    Article  Google Scholar 

  • Spiesz EM, Thorpe CT, Chaudhry S, Riley GP, Birch HL, Clegg PD, Screen HR (2015) Tendon extracellular matrix damage, degradation and inflammation in response to in vitro overload exercise. J Orthop Res 33:889–897

    Article  Google Scholar 

  • Stanley RL, Fleck RA, Becker DL, Goodship AE, Ralphs JR, Patterson-Kane JC (2007) Gap junction protein expression and cellularity: comparison of immature and adult equine digital tendons. J Anat 211:325–334

    Article  Google Scholar 

  • Stenroth L, Peltonen J, Cronin NJ, Sipila S, Finni T (2012) Age-related differences in Achilles tendon properties and triceps surae muscle architecture in vivo. J Appl Physiol (1985) 113:1537–1544

    Article  Google Scholar 

  • Sugg KB, Lubardic J, Gumucio JP, Mendias CL (2014) Changes in macrophage phenotype and induction of epithelial-to-mesenchymal transition genes following acute Achilles tenotomy and repair. J Orthop Res 32:944–951

    Article  Google Scholar 

  • Sugimoto Y, Takimoto A, Akiyama H, Kist R, Scherer G, Nakamura T, Hiraki Y, Shukunami C (2013) Scx+/Sox9+ progenitors contribute to the establishment of the junction between cartilage and tendon/ligament. Development 140:2280–2288

    Article  Google Scholar 

  • Tan Q, Lui PP, Lee YW (2013) In vivo identity of tendon stem cells and the roles of stem cells in tendon healing. Stem Cells Dev 22:3128–3140

    Article  Google Scholar 

  • Tempfer H, Traweger A (2015) Tendon vasculature in health and disease. Front Physiol 6:330

    Article  Google Scholar 

  • Tempfer H, Wagner A, Gehwolf R, Lehner C, Tauber M, Resch H, Bauer HC (2009) Perivascular cells of the supraspinatus tendon express both tendon- and stem cell-related markers. Histochem Cell Biol 131:733–741

    Article  Google Scholar 

  • Tetta C, Consiglio AL, Bruno S, Tetta E, Gatti E, Dobreva M, Cremonesi F, Camussi G (2012) The role of microvesicles derived from mesenchymal stem cells in tissue regeneration; a dream for tendon repair? Muscles Ligaments Tendons J 2:212–221

    Google Scholar 

  • Teunis T, Lubberts B, Reilly BT, Ring D (2014) A systematic review and pooled analysis of the prevalence of rotator cuff disease with increasing age. J Shoulder Elbow Surg 23:1913–1921

    Article  Google Scholar 

  • Thomopoulos S, Genin GM, Galatz LM (2010) The development and morphogenesis of the tendon-to-bone insertion – what development can teach us about healing. J Musculoskelet Neuronal Interact 10:35–45

    Google Scholar 

  • Thorpe CT, Streeter I, Pinchbeck GL, Goodship AE, Clegg PD, Birch HL (2010) Aspartic acid racemization and collagen degradation markers reveal an accumulation of damage in tendon collagen that is enhanced with aging. J Biol Chem 285:15674–15681

    Article  Google Scholar 

  • Thorpe CT, Birch HL, Clegg PD, Screen HR (2013) The role of the non-collagenous matrix in tendon function. Int J Exp Pathol 94:248–259

    Article  Google Scholar 

  • Tokunaga T, Shukunami C, Okamoto N, Taniwaki T, Oka K, Sakamoto H, Ide J, Mizuta H, Hiraki Y (2015) FGF-2 stimulates the growth of Tenogenic progenitor cells to facilitate the generation of Tenomodulin-positive tenocytes in a rat rotator cuff healing model. Am J Sports Med 43:2411–2422

    Article  Google Scholar 

  • Tsai WC, Chang HN, Yu TY, Chien CH, Fu LF, Liang FC, Pang JH (2011) Decreased proliferation of aging tenocytes is associated with down-regulation of cellular senescence-inhibited gene and up-regulation of p27. J Orthop Res 29:1598–1603

    Article  Google Scholar 

  • Tsimbouri PM (2015) Adult stem cell responses to Nanostimuli. J Funct Biomater 6:598–622

    Article  Google Scholar 

  • Usuelli FG, Grassi M, Maccario C, Vigano M, Lanfranchi L, Alfieri Montasio U, de Girolamo L (2017) Intratendinous adipose-derived stromal vascular fraction (SVF) injection provides a safe, efficacious treatment for Achilles tendinopathy: results of a randomized controlled clinical trial at a 6-month follow-up. Knee Surg Sports Traumatol Arthros. https://doi.org/10.1007/s00167-017-4479-9

  • Veronesi F, Salamanna F, Tschon M, Maglio M, Nicoli Aldini N, Fini M (2016) Mesenchymal stem cells for tendon healing: what is on the horizon? J Tissue Eng Regen Med 40:555

    Google Scholar 

  • Violini S, Ramelli P, Pisani LF, Gorni C, Mariani P (2009) Horse bone marrow mesenchymal stem cells express embryo stem cell markers and show the ability for tenogenic differentiation by in vitro exposure to BMP-12. BMC Cell Biol 10:29

    Article  Google Scholar 

  • Vogel KG, Ordog A, Pogany G, Olah J (1993) Proteoglycans in the compressed region of human tibialis posterior tendon and in ligaments. J Orthop Res 11:68–77

    Article  Google Scholar 

  • Voleti PB, Buckley MR, Soslowsky LJ (2012) Tendon healing: repair and regeneration. Annu Rev Biomed Eng 14:47–71

    Article  Google Scholar 

  • Vorbruggen G, Jackle H (1997) Epidermal muscle attachment site-specific target gene expression and interference with myotube guidance in response to ectopic stripe expression in the developing drosophila epidermis. Proc Natl Acad Sci U S A 94:8606–8611

    Article  Google Scholar 

  • Wang JH (2006) Mechanobiology of tendon. J Biomech 39:1563–1582

    Article  Google Scholar 

  • Wang JH, Guo Q, Li B (2012) Tendon biomechanics and mechanobiology – a minireview of basic concepts and recent advancements. J Hand Ther 25:133–140. quiz 141

    Article  Google Scholar 

  • Wang A, Breidahl W, Mackie KE, Lin Z, Qin A, Chen J, Zheng MH (2013) Autologous tenocyte injection for the treatment of severe, chronic resistant lateral epicondylitis: a pilot study. Am J Sports Med 41:2925–2932

    Article  Google Scholar 

  • Wang A, Mackie K, Breidahl W, Wang T, Zheng MH (2015) Evidence for the durability of autologous tenocyte injection for treatment of chronic resistant lateral epicondylitis: mean 4.5-year clinical follow-up. Am J Sports Med 43:1775–1783

    Article  Google Scholar 

  • Wenstrup RJ, Florer JB, Brunskill EW, Bell SM, Chervoneva I, Birk DE (2004) Type V collagen controls the initiation of collagen fibril assembly. J Biol Chem 279:53331–53337

    Article  Google Scholar 

  • Wu H, Zhao G, Zu H, Wang JH, Wang QM (2015) Aging-related viscoelasticity variation of tendon stem cells (TSCs) characterized by quartz thickness shear mode (TSM) resonators. Sens Actuators (Warrendale) 210:369–380

    Article  Google Scholar 

  • Xu W, Sun Y, Zhang J, Xu K, Pan L, He L, Song Y, Njunge L, Xu Z, Chiang MY, Sung KL, Chuong CM, Yang L (2015) Perivascular-derived stem cells with neural crest characteristics are involved in tendon repair. Stem Cells Dev 24:857–868

    Article  Google Scholar 

  • Yang G, Rothrauff BB, Tuan RS (2013) Tendon and ligament regeneration and repair: clinical relevance and developmental paradigm. Birth Defects Res C Embryo Today 99:203–222

    Article  Google Scholar 

  • Yin Z, Chen X, Chen JL, Ouyang HW (2010a) Stem cells for tendon tissue engineering and regeneration. Expert Opin Biol Ther 10:689–700

    Article  Google Scholar 

  • Yin Z, Chen X, Chen JL, Shen WL, Hieu Nguyen TM, Gao L, Ouyang HW (2010b) The regulation of tendon stem cell differentiation by the alignment of nanofibers. Biomaterials 31:2163–2175

    Article  Google Scholar 

  • Yu TY, Pang JH, Wu KP, Chen MJ, Chen CH, Tsai WC (2013) Aging is associated with increased activities of matrix metalloproteinase-2 and -9 in tenocytes. BMC Musculoskelet Disord 14:2

    Article  Google Scholar 

  • Zelzer E, Blitz E, Killian ML, Thomopoulos S (2014) Tendon-to-bone attachment: from development to maturity. Birth Defects Res C Embryo Today 102:101–112

    Article  Google Scholar 

  • Zhang J, Wang JH (2010a) Characterization of differential properties of rabbit tendon stem cells and tenocytes. BMC Musculoskelet Disord 11:10

    Article  Google Scholar 

  • Zhang J, Wang JH (2010b) Mechanobiological response of tendon stem cells: implications of tendon homeostasis and pathogenesis of tendinopathy. J Orthop Res 28:639–643

    Article  Google Scholar 

  • Zhang J, Wang JH (2010c) Production of PGE(2) increases in tendons subjected to repetitive mechanical loading and induces differentiation of tendon stem cells into non-tenocytes. J Orthop Res 28:198–203

    Article  Google Scholar 

  • Zhang J, Wang JH (2012) BMP-2 mediates PGE(2) -induced reduction of proliferation and osteogenic differentiation of human tendon stem cells. J Orthop Res 30:47–52

    Article  Google Scholar 

  • Zhang J, Wang JH (2013a) The effects of mechanical loading on tendons – an in vivo and in vitro model study. PLoS One 8:e71740

    Article  Google Scholar 

  • Zhang J, Wang JH (2013b) Human tendon stem cells better maintain their stemness in hypoxic culture conditions. PLoS One 8:e61424

    Article  Google Scholar 

  • Zhang J, Pan T, Liu Y, Wang JH (2010a) Mouse treadmill running enhances tendons by expanding the pool of tendon stem cells (TSCs) and TSC-related cellular production of collagen. J Orthop Res 28:1178–1183

    Article  Google Scholar 

  • Zhang Y, Wang B, Zhang WJ, Zhou G, Cao Y, Liu W (2010b) Enhanced proliferation capacity of porcine tenocytes in low O2 tension culture. Biotechnol Lett 32:181–187

    Article  Google Scholar 

  • Zhang K, Asai S, Yu B, Enomoto-Iwamoto M (2015) IL-1beta irreversibly inhibits tenogenic differentiation and alters metabolism in injured tendon-derived progenitor cells in vitro. Biochem Biophys Res Commun 463:667–672

    Article  Google Scholar 

  • Zhang L, Chen S, Chang P, Bao N, Yang C, Ti Y, Zhou L, Zhao J (2016) Harmful effects of leukocyte-rich platelet-rich plasma on rabbit tendon stem cells in vitro. Am J Sports Med 44:1941–1951

    Article  Google Scholar 

  • Zhou Z, Akinbiyi T, Xu L, Ramcharan M, Leong DJ, Ros SJ, Colvin AC, Schaffler MB, Majeska RJ, Flatow EL, Sun HB (2010) Tendon-derived stem/progenitor cell aging: defective self-renewal and altered fate. Aging Cell 9:911–915

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Tendon and Bone Regeneration, Paracelsus Medical University, Spinal Cord Injury & Tissue Regeneration Center Salzburg, Austria, Strubergasse 22, A-5020, Salzburg, Austria

    Herbert Tempfer, Christine Lehner, Moritz Grütz, Renate Gehwolf & Andreas Traweger

  2. Austrian Cluster for Tissue Regeneration, Vienna, Austria

    Herbert Tempfer, Christine Lehner, Moritz Grütz, Renate Gehwolf & Andreas Traweger

  3. University of Salzburg, Salzburg, Austria

    Herbert Tempfer & Andreas Traweger

Authors
  1. Herbert Tempfer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christine Lehner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Moritz Grütz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Renate Gehwolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andreas Traweger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Herbert Tempfer .

Editor information

Editors and Affiliations

  1. Tulane Univ. Sch. of Medicine, New Orleans, Louisiana, USA

    Jeffrey M. Gimble

  2. AUVA Center, Ludwig Boltzmann Institute for Experimen, Vienna, Austria

    Darja Marolt

  3. Human Development and Health, University of Southampton, Southampton, United Kingdom

    Richard Oreffo

  4. Experimental and Clinical Traumatol, Ludwig Boltzmann Institute for, Wien, Austria

    Heinz Redl

  5. AUVA Center, Ludwig Boltzmann Institute for Experimen, Vienna, Austria

    Susanne Wolbank

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this entry

Cite this entry

Tempfer, H., Lehner, C., Grütz, M., Gehwolf, R., Traweger, A. (2017). Biological Augmentation for Tendon Repair: Lessons to be Learned from Development, Disease, and Tendon Stem Cell Research. In: Gimble, J., Marolt, D., Oreffo, R., Redl, H., Wolbank, S. (eds) Cell Engineering and Regeneration. Reference Series in Biomedical Engineering(). Springer, Cham. https://doi.org/10.1007/978-3-319-37076-7_54-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-37076-7_54-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-37076-7

  • Online ISBN: 978-3-319-37076-7

  • eBook Packages: Springer Reference EngineeringReference Module Computer Science and Engineering

Publish with us

Policies and ethics

Search

Navigation