Skip to main content
SpringerLink
Log in

Multiscale Multifactorial Approaches for Engineering Tendon Substitutes

  • Living reference work entry
  • First Online:
Organ Tissue Engineering

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

Abstract

The physiology of tendons and the continuous strains experienced daily make tendons very prone to injury. Excessive and prolonged loading forces and aging also contribute to the onset and progression of tendon injuries, and conventional treatments have limited efficacy in restoring tendon biomechanics. Tissue engineering and regenerative medicine (TERM) approaches hold the promise to provide therapeutic solutions for injured or damaged tendons despite the challenging cues of tendon niche and the lack of tendon-specific factors to guide cellular responses and tackle regeneration. The roots of engineering tendon substitutes lay in multifactorial approaches from adequate stem cells sources and environmental stimuli to the construction of multiscale 3D scaffolding systems.

To achieve such advanced tendon substitutes, incremental strategies have been pursued to more closely recreate the native tendon requirements providing structural as well as physical and chemical cues combined with biochemical and mechanical stimuli to instruct cell behavior in 3D architectures, pursuing mechanically competent constructs with adequate maturation before implantation.

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

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Almeida H, Domingues RMA, Mithieux SM, Pires RA, Gonçalves AI, Gómez-Florit M, Reis RL, Weiss AS, Gomes ME (2019) Tropoelastin-coated tendon biomimetic scaffolds promote stem cell Tenogenic commitment and deposition of elastin-rich matrix. ACS Appl Mater Interfaces 11(22):19830–19840

    Google Scholar 

  • Baldwin M, Snelling S, Dakin S, Carr A (2018) Augmenting endogenous repair of soft tissues with nanofibre scaffolds. J R Soc Interface 15(141)

    Google Scholar 

  • Barber JG, Handorf AM, Allee TJ, Li WJ (2013) Braided nanofibrous scaffold for tendon and ligament tissue engineering. Tissue Eng Part A 19(11–12):1265–1274

    Google Scholar 

  • Barsby T, Guest D (2013) Transforming growth factor Beta3 promotes tendon differentiation of equine embryo-derived stem cells. Tissue Eng A 19(19–20):2156–2165

    Google Scholar 

  • Bashur CA, Shaffer RD, Dahlgren LA, Guelcher SA, Goldstein AS (2009) Effect of fiber diameter and alignment of electrospun polyurethane meshes on mesenchymal progenitor cells. Tissue Eng Part A 15(9):2435–2445

    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(10):1219–1227

    Google Scholar 

  • Bracaglia LG, Smith BT, Watson E, Arumugasaamy N, Mikos AG, Fisher JP (2017) 3D printing for the design and fabrication of polymer-based gradient scaffolds. Acta Biomater 56:3–13

    Google Scholar 

  • Brennan DA, Conte AA, Kanski G, Turkula S, Hu X, Kleiner MT, Beachley V (2018) Mechanical considerations for electrospun nanofibers in tendon and ligament repair. Adv Healthc Mater 7(12):e1701277

    Google Scholar 

  • Brent AE, Schweitzer R, Tabin CJ (2003) A somitic compartment of tendon progenitors. Cell 113(2):235–248

    Google Scholar 

  • Cadby JA, Buehler E, Godbout C, van Weeren PR, Snedeker JG (2014) Differences between the cell populations from the peritenon and the tendon core with regard to their potential implication in tendon repair. PLoS One 9(3):e92474

    Google Scholar 

  • Chainani A, Hippensteel KJ, Kishan A, Garrigues NW, Ruch DS, Guilak F, Little D (2013) Multilayered electrospun scaffolds for tendon tissue engineering. Tissue Eng Part A 19(23–24):2594–2604

    Google Scholar 

  • Cheng X, Tsao C, Sylvia VL, Cornet D, Nicolella DP, Bredbenner TL, Christy RJ (2014) Platelet-derived growth-factor-releasing aligned collagen-nanoparticle fibers promote the proliferation and tenogenic differentiation of adipose-derived stem cells. Acta Bio 10(3):1360–1369

    Google Scholar 

  • Czaplewski SK, Tsai TL, Duenwald-Kuehl SE, Vanderby R Jr, Li WJ (2014) Tenogenic differentiation of human induced pluripotent stem cell-derived mesenchymal stem cells dictated by properties of braided submicron fibrous scaffolds. Biomaterials 35(25):6907–6917

    Google Scholar 

  • Dalby MJ, García AJ, Salmeron-Sanchez M (2018) Receptor control in mesenchymal stem cell engineering. Nat Rev Mater 3:17091

    Google Scholar 

  • Dale TP, Mazher S, Webb WR, Zhou J, Maffulli N, Chen GQ, El Haj AJ, Forsyth NR (2018) Tenogenic differentiation of human embryonic stem cells. Tissue Eng Part A 24(5–6):361–368

    Google Scholar 

  • de Aro AA, Vidal BD, Pimentel ER (2012) Biochemical and anisotropical properties of tendons. Micron 43(2–3):205–214

    Google Scholar 

  • de Mos M, Koevoet WJ, Jahr H, Verstegen MM, Heijboer MP, Kops N, van Leeuwen JP, Weinans H, Verhaar JA, van Osch GJ (2007) Intrinsic differentiation potential of adolescent human tendon tissue: an in-vitro cell differentiation study. BMC Musculoskelet Disord 8:16

    Google Scholar 

  • Derakhshanfar S, Mbeleck R, Xu K, Zhang X, Zhong W, Xing M (2018) 3D bioprinting for biomedical devices and tissue engineering: a review of recent trends and advances. Bioact Mater 3(2):144–156

    Google Scholar 

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

    Google Scholar 

  • Domingues RM, Chiera S, Gershovich P, Motta A, Reis RL, Gomes ME (2016) Enhancing the biomechanical performance of anisotropic Nanofibrous scaffolds in tendon tissue engineering: reinforcement with cellulose nanocrystals. Adv Healthc Mater 5(11):1364–1375

    Google Scholar 

  • Dyment NA, Liu C-F, 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(3):e59944

    Google Scholar 

  • Engebretson B, Mussett ZR, Sikavitsas VI (2017) Tenocytic extract and mechanical stimulation in a tissue-engineered tendon construct increases cellular proliferation and ECM deposition. Biotechnol J 12(3):1–26

    Google Scholar 

  • Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126(4):677–689

    Google Scholar 

  • English A, Azeem A, Spanoudes K, Jones E, Tripathi B, Basu N, McNamara K, Tofail SAM, Rooney N, Riley G, O’Riordan A, Cross G, Hutmacher D, Biggs M, Pandit A, Zeugolis DI (2015) Substrate topography: a valuable in vitro tool, but a clinical red herring for in vivo tenogenesis. Acta Biomater 27:3–12

    Google Scholar 

  • Erisken C, Zhang X, Moffat KL, Levine WN, Lu HH (2013a) Scaffold fiber diameter regulates human tendon fibroblast growth and differentiation. Tissue Eng Part A 19(3–4):519–528

    Google Scholar 

  • Erisken C, Zhang X, Moffat KL, Levine WN, Lu HH (2013b) Scaffold Fiber diameter regulates human tendon fibroblast growth and differentiation. Tissue Eng A 19(3–4):519–528

    Google Scholar 

  • Farhat YM, Al-Maliki AA, Chen T, Juneja SC, Schwarz EM, O’Keefe RJ, Awad HA (2012) Gene expression analysis of the pleiotropic effects of TGF-beta 1 in an in vitro model of flexor tendon healing. PLoS One 7(12):12

    Google Scholar 

  • Font Tellado S, Chiera S, Bonani W, Poh PSP, Migliaresi C, Motta A, Balmayor ER, van Griensven M (2018) Heparin functionalization increases retention of TGF-β2 and GDF5 on biphasic silk fibroin scaffolds for tendon/ligament-to-bone tissue engineering. Acta Biomater 72:150–166

    Google Scholar 

  • Freeman JW, Woods MD, Laurencin CT (2007) Tissue engineering of the anterior cruciate ligament using a braid – twist scaffold design. 40:2029–2036

    Google Scholar 

  • Gilchrist CL, Ruch DS, Little D, Guilak F (2014) Micro-scale and meso-scale architectural cues cooperate and compete to direct aligned tissue formation. Biomaterials 35(38):10015–10024

    Google Scholar 

  • Gonçalves AI, Rodrigues MT, Lee SJ, Atala A, Yoo JJ, Reis RL, Gomes ME (2013) Understanding the role of growth factors in modulating stem cell tenogenesis. PLoS One 8(12):e83734

    Google Scholar 

  • Goncalves AI, Rodrigues MT, Carvalho PP, Banobre-Lopez M, Paz E, Freitas P, Gomes ME (2016) Exploring the potential of starch/Polycaprolactone aligned magnetic responsive scaffolds for tendon regeneration. Adv Healthc Mater 5(2):213–222

    Google Scholar 

  • Gonçalves AI, Berdecka D, Rodrigues MT, Reis RL, Gomes ME (2018) Bioreactors for tendon tissue engineering: challenging mechanical demands towards tendon regeneration. Bioreactors for stem cell expansion and differentiation. CRC Press, Boca Raton, pp 269–300

    Google Scholar 

  • Goncalves AI, Gershovich PM, Rodrigues MT, Reis RL, Gomes ME (2018a) Human adipose tissue-derived tenomodulin positive subpopulation of stem cells: a promising source of tendon progenitor cells. J Tissue Eng Regen Med 12(3):762–774

    Google Scholar 

  • Goncalves AI, Rotherham M, Markides H, Rodrigues MT, Reis RL, Gomes ME, El Haj AJ (2018b) Triggering the activation of Activin a type II receptor in human adipose stem cells towards tenogenic commitment using mechanomagnetic stimulation. Nanomed Nanotechnol Biol Med 14(4):1149–1159

    Google Scholar 

  • Goncalves AI, Berdecka D, Rodrigues MT, Eren AD, de Boer J, Reis RL, Gomes ME (2019) Evaluation of tenogenic differentiation potential of selected subpopulations of human adipose-derived stem cells. J Tissue Eng Regen Med 13(12):2204–2217

    Google Scholar 

  • Hakimi O, Mouthuy PA, Zargar N, Lostis E, Morrey M, Carr A (2015) A layered electrospun and woven surgical scaffold to enhance endogenous tendon repair. Acta Biomater 26:124–135

    Google Scholar 

  • Havis E, Bonnin M-A, Olivera-Martinez I, Nazaret N, Ruggiu M, Weibel J, Durand C, Guerquin M-J, Bonod-Bidaud C, Ruggiero F (2014a) Transcriptomic analysis of mouse limb tendon cells during development. Development 141(19):3683–3696

    Google Scholar 

  • Havis E, Bonnin MA, Olivera-Martinez I, Nazaret N, Ruggiu M, Weibel J, Durand C, Guerquin MJ, Bonod-Bidaud C, Ruggiero F, Schweitzer R, Duprez D (2014b) Transcriptomic analysis of mouse limb tendon cells during development. Development 141(19):3683–3696

    Google Scholar 

  • Havis E, Bonnin MA, de Lima JE, 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(20):3839–3851

    Google Scholar 

  • Izu Y, Ansorge HL, Zhang GY, Soslowsky LJ, Bonaldo P, Chu ML, Birk DE (2011) Dysfunctional tendon collagen fibrillogenesis in collagen VI null mice. Matrix Biol 30(1):53–61

    Google Scholar 

  • Jayasree A, Kottappally Thankappan S, Ramachandran R, Sundaram MN, Chen C-H, Mony U, Chen J-P, Jayakumar R (2019) Bioengineered braided micro–Nano (multiscale) fibrous scaffolds for tendon reconstruction. ACS Biomater Sci Eng 5(3):1476–1486

    Google Scholar 

  • Jenkins TL, Little D (2019) Synthetic scaffolds for musculoskeletal tissue engineering: cellular responses to fiber parameters. npj Regen Med 4(1):1–14

    Google Scholar 

  • Katsura T, Tohyama H, Kondo E, Kitamura N, Yasuda K (2006) Effects of administration of transforming growth factor (TGF)-beta1 and anti-TGF-beta1 antibody on the mechanical properties of the stress-shielded patellar tendon. J Biomech 39(14):2566–2572

    Google Scholar 

  • Killian ML, Cavinatto L, Galatz LM, Thomopoulos S (2012) The role of mechanobiology in tendon healing. J Shoulder Elb Surg 21(2):228–237

    Google Scholar 

  • Kishore V, Bullock W, Sun X, Van Dyke WS, Akkus O (2012) Tenogenic differentiation of human MSCs induced by the topography of electrochemically aligned collagen threads. Biomaterials 33(7):2137–2144

    Google Scholar 

  • Laranjeira M, Domingues RMA, Costa-Almeida R, Reis RL, Gomes ME (2017) 3D mimicry of native-tissue-Fiber architecture guides tendon-derived cells and adipose stem cells into artificial tendon constructs. Small 13(31)

    Google Scholar 

  • Laternser S, Keller H, Leupin O, Rausch M, Graf-Hausner U, Rimann M (2018) A novel microplate 3D bioprinting platform for the engineering of muscle and tendon tissues. SLAS Technol 23(6):599–613

    Google Scholar 

  • Lavagnino M, Wall ME, Little D, Banes AJ, Guilak F, Arnoczky SP (2015) Tendon Mechanobiology: current knowledge and future research opportunities. J Orthop Res 33(6):813–822

    Google Scholar 

  • Lee CH, Yang G, Mao JJ, Lee CH, Lee FY, Tarafder S, Kao K, Jun Y, Yang G, Mao JJ (2015) Harnessing endogenous stem/progenitor cells for tendon regeneration find the latest version: harnessing endogenous stem/progenitor cells for tendon regeneration. 125(7):2690–2701

    Google Scholar 

  • Lee NM, Erisken C, Iskratsch T, Sheetz M, Levine WN, Lu HH (2017) Polymer fiber-based models of connective tissue repair and healing. Biomaterials 112:303–312

    Google Scholar 

  • Leung M, Jana S, Tsao C-T, Zhang M (2013) Tenogenic differentiation of human bone marrow stem cells via a combinatory effect of aligned chitosan-poly-caprolactone nanofibers and TGF-β3. J Mater Chem B 1:6516–6524

    Google Scholar 

  • Lim PN, Wang Z, Wang D, Konishi T, San Thian E (2017) Development in additive printing for tissue-engineered bone and tendon regeneration. Curr Opin Biomed Eng 2:99–104

    Google Scholar 

  • Lin TW, Cardenas L, Soslowsky LJ (2004) Biomechanics of tendon injury and repair. J Biomech 37(6):865–877

    Google Scholar 

  • Lin J, Zhou W, Han S, Bunpetch V, Zhao K, Liu C, Yin Z, Ouyang H (2018) Cell-material interactions in tendon tissue engineering. Acta Biomater 70:1–11

    Google Scholar 

  • Lipman K, Wang CC, Ting K, Soo C, Zheng Z (2018) Tendinopathy: injury, repair, and current exploration. Drug Des Devel Ther 12:591–603

    Google Scholar 

  • Liu HH, Zhang C, Zhu SA, Lu P, Zhu T, Gong XN, Zhang ZW, Hu JJ, Yin Z, Heng BC, Chen X, Ouyang HW (2015) Mohawk promotes the Tenogenesis of mesenchymal stem cells through activation of the TGF beta signaling pathway. Stem Cells 33(2):443–455

    Google Scholar 

  • Madhurakkat Perikamana SK, Lee J, Ahmad T, Kim EM, Byun H, Lee S, Shin H (2018) Harnessing biochemical and structural cues for tenogenic differentiation of adipose derived stem cells (ADSCs) and development of an in vitro tissue interface mimicking tendon-bone insertion graft. Biomaterials 165:79–93

    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(11):933–941

    Google Scholar 

  • Magnusson SP, Hansen P, Kjaer M (2003) Tendon properties in relation to muscular activity and physical training. Scand J Med Sci Sports 13(4):211–223

    Google Scholar 

  • Merceron TK, Burt M, Seol YJ, Kang HW, Lee SJ, Yoo JJ, Atala A (2015) A 3D bioprinted complex structure for engineering the muscle-tendon unit. Biofabrication 7(3):035003

    Google Scholar 

  • Mienaltowski MJ, Adams SM, Birk DE (2014) Tendon proper- and peritenon-derived progenitor cells have unique tenogenic properties. Stem Cell Res Ther 5(4):86

    Google Scholar 

  • Mihaila SM, Frias AM, Pirraco RP, Rada T, Reis RL, Gomes ME, Marques AP (2013) Human adipose tissue-derived SSEA-4 subpopulation multi-differentiation potential towards the endothelial and osteogenic lineages. Tissue Eng Part A 19(1–2):235–246

    Google Scholar 

  • Mihaila SM, Gaharwar AK, Reis RL, Khademhosseini A, Marques AP, Gomes ME (2014) The osteogenic differentiation of SSEA-4 sub-population of human adipose derived stem cells using silicate nanoplatelets. Biomaterials 35(33):9087–9099

    Google Scholar 

  • Mihaila SM, Resende MF, Reis RL, Gomes ME, Marques AP (2015) Interactive endothelial phenotype maintenance and osteogenic differentiation of adipose tissue stromal vascular fraction SSEA-4+-derived cells. J Tissue Eng Regen Med

    Google Scholar 

  • Millar NL, Gilchrist DS, Akbar M, Reilly JH, Kerr SC, Campbell AL, Murrell GAC, Liew FY, Kurowska-Stolarska M, McInnes IB (2015) MicroRNA29a regulates IL-33-mediated tissue remodelling in tendon disease. Nat Commun 6:13

    Google Scholar 

  • Min HK, Oh SH, Lee JM, Im GI, Lee JH (2014) Porous membrane with reverse gradients of PDGF-BB and BMP-2 for tendon-to-bone repair: in vitro evaluation on adipose-derived stem cell differentiation. Acta Biomater 10(3):1272–1279

    Google Scholar 

  • Miranda-Nieves D, Chaikof EL (2017) Collagen and elastin biomaterials for the fabrication of engineered living tissues. ACS Biomater Sci Eng 3(5):694–711

    Google Scholar 

  • Miranville A, Heeschen C, Sengenes C, Curat CA, Busse R, Bouloumie A (2004) Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation 110(3):349–355

    Google Scholar 

  • Moffat KL, Kwei ASP, Spalazzi JP, Doty SB, Levine WN, Lu HH (2009) Novel nanofiber-based scaffold for rotator cuff repair and augmentation. Tissue Eng A 15(1):115–126

    Google Scholar 

  • Moroni L, Boland T, Burdick JA, De Maria C, Derby B, Forgacs G, Groll J, Li Q, Malda J, Mironov VA, Mota C, Nakamura M, Shu W, Takeuchi S, Woodfield TBF, Xu T, Yoo JJ, Vozzi G (2018a) Biofabrication: a guide to technology and terminology. Trends Biotechnol 36(4):384–402

    Google Scholar 

  • Moroni L, Burdick JA, Highley C, Lee SJ, Morimoto Y, Takeuchi S, Yoo JJ (2018b) Biofabrication strategies for 3D in vitro models and regenerative medicine. Nat Rev Mater 3:5

    Google Scholar 

  • Muller SA, Evans CH, Heisterbach PE, Majewski M (2018) The role of the Paratenon in Achilles tendon healing: a study in rats. Am J Sports Med 46(5):1214–1219

    Google Scholar 

  • Orr SB, Chainani A, Hippensteel KJ, Kishan A, Gilchrist C, Garrigues NW, Ruch DS, Guilak F, Little D (2015) Aligned multilayered electrospun scaffolds for rotator cuff tendon tissue engineering. Acta Biomater 24:117–126

    Google Scholar 

  • Park SH, Choi YJ, Moon SW, Lee BH, Shim JH, Cho DW, Wang JH (2018) Three-dimensional bio-printed scaffold sleeves with mesenchymal stem cells for enhancement of tendon-to-bone healing in anterior cruciate ligament reconstruction using soft-tissue tendon graft. Arthroscopy 34(1):166–179

    Google Scholar 

  • Pauly HM, Sathy BN, Olvera D, McCarthy HO, Kelly DJ, Popat KC, Dunne NJ, Haut Donahue TL (2017) Hierarchically structured electrospun scaffolds with chemically conjugated growth factor for ligament tissue engineering. Tissue Eng Part A 23(15–16):823–836

    Google Scholar 

  • Perucca Orfei C, Vigano M, Pearson JR, Colombini A, De Luca P, Ragni E, Santos-Ruiz L, de Girolamo L (2019) In vitro induction of tendon-specific markers in tendon cells, adipose- and bone marrow-derived stem cells is dependent on TGFbeta3, BMP-12 and ascorbic acid stimulation. Int J Mol Sci 20(1)

    Google Scholar 

  • Qin TW, Yang ZM, Wu ZZ, Xie HQ, Qin J, Cai SX (2005) Adhesion strength of human tenocytes to extracellular matrix component-modified poly(DL-lactide-co-glycolide) substrates. Biomaterials 26(33):6635–6642

    Google Scholar 

  • Rada T, Gomes ME, Reis RL (2011a) A novel method for the isolation of subpopulations of rat adipose stem cells with different proliferation and osteogenic differentiation potentials. J Tissue Eng Regen Med 5(8):655–664

    Google Scholar 

  • Rada T, Reis RL, Gomes ME (2011b) Distinct stem cells subpopulations isolated from human adipose tissue exhibit different chondrogenic and osteogenic differentiation potential. Stem Cell Rev 7(1):64–76

    Google Scholar 

  • Rada T, Santos TC, Marques AP, Correlo VM, Frias AM, Castro AG, Neves NM, Gomes ME, Reis RL (2012) Osteogenic differentiation of two distinct subpopulations of human adipose-derived stem cells: an in vitro and in vivo study. J Tissue Eng Regen Med 6(1):1–11

    Google Scholar 

  • Rees JD, Wilson AM, Wolman RL (2006) Current concepts in the management of tendon disorders. Rheumatology 45(5):508–521

    Google Scholar 

  • Riehl BD, Park JH, Kwon IK, Lim JY (2012) Mechanical stretching for tissue engineering: two-dimensional and three-dimensional constructs. Tissue Eng Part B Rev 18(4):288–300

    Google Scholar 

  • Riley G (2004) The pathogenesis of tendinopathy. A molecular perspective. Rheumatology 43(2):131–142

    Google Scholar 

  • Rinoldi C, Costantini M, Kijeńska-Gawrońska E, Testa S, Fornetti E, Heljak M, Ćwiklińska M, Buda R, Baldi J, Cannata S, Guzowski J, Gargioli C, Khademhosseini A, Swieszkowski W (2019) Tendon tissue engineering: effects of mechanical and biochemical stimulation on stem cell alignment on cell-laden hydrogel yarns. Adv Healthc Mater 8(7):1–10

    Google Scholar 

  • Rodrigues MT, Reis RL, Gomes ME (2013) Engineering tendon and ligament tissues: present developments towards successful clinical products. J Tissue Eng Regen Med 7(9):673–686

    Google Scholar 

  • Rothrauff BB, Lauro BB, Yang G, Debski RE, Musahl V, Tuan RS (2017) Braided and stacked electrospun Nanofibrous scaffolds for tendon and ligament tissue engineering. Tissue Eng Part A 23(9–10):378–389

    Google Scholar 

  • Sahoo S, Toh SL, Goh JCH (2010) A bFGF-releasing silk/PLGA-based biohybrid scaffold for ligament/tendon tissue engineering using mesenchymal progenitor cells. Biomaterials 31(11):2990–2998

    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(2):289–300

    Google Scholar 

  • Santos LJ, Reis RL, Gomes ME (2015) Harnessing magnetic-mechano actuation in regenerative medicine and tissue engineering. Trends Biotechnol 33(8):471–479

    Google Scholar 

  • Santos ML, Rodrigues MT, Domingues RM, Reis RL, Gomes ME (2017) Biomaterials as tendon and ligament substitutes: current developments. In: Regenerative strategies for the treatment of knee joint disabilities, vol 21. Springer, pp 349–371

    Google Scholar 

  • Schmierer B, Hill CS (2007) TGF beta-SMAD signal transduction: molecular specificity and functional flexibility. Nat Rev Mol Cell Biol 8(12):970–982

    Google Scholar 

  • Schneider M, Angele P, Jarvinen TAH, Docheva D (2017) Rescue plan for Achilles: therapeutics steering the fate and functions of stem cells in tendon wound healing. Adv Drug Deliv Rev

    Google Scholar 

  • Schoenenberger AD, Foolen J, Moor P, Silvan U, Snedeker JG (2018) Substrate fiber alignment mediates tendon cell response to inflammatory signaling. Acta Biomater 71:306–317

    Google Scholar 

  • Screen HRC, Berk DE, Kadler KE, Ramirez F, Young MF (2015) Tendon Functional Extracellular Matrix. J Orthop Res 33(6):793–799

    Google Scholar 

  • Sengenes C, Miranville A, Maumus M, de Barros S, Busse R, Bouloumie A (2007) Chemotaxis and differentiation of human adipose tissue CD34+/CD31- progenitor cells: role of stromal derived factor-1 released by adipose tissue capillary endothelial cells. Stem Cells 25(9):2269–2276

    Google Scholar 

  • Sharma P, Maffulli N (2005) Current concepts review tendon injury and tendinopathy: healing and repair. J Bone Joint Surg Am 87A(1):187–202

    Google Scholar 

  • Sharma P, Maffulli N (2006) Biology of tendon injury: healing, modeling and remodeling. J Musculoskelet Nueronal Interact 6(2):181

    Google Scholar 

  • Sharma RI, Snedeker JG (2010) Biochemical and biomechanical gradients for directed bone marrow stromal cell differentiation toward tendon and bone. Biomaterials 31(30):7695–7704

    Google Scholar 

  • Shen H, Gelberman RH, Silva MJ, Sakiyama-Elbert SE, Thomopoulos S (2013) BMP12 induces tenogenic differentiation of adipose-derived stromal cells. PLoS One 8(10):1–14

    Google Scholar 

  • Shen H, Jayaram R, Yoneda S, Linderman SW, Sakiyama-Elbert SE, Xia Y, Gelberman RH, Thomopoulos S (2018) The effect of adipose-derived stem cell sheets and CTGF on early flexor tendon healing in a canine model. Sci Rep 8(1):11078

    Google Scholar 

  • Soslowsky LJ, Thomopoulos S, Tun S, Flanagan CL, Keefer CC, Mastaw J, Carpenter JE (2000) Neer award 1999 – overuse activity injures the supraspinatus tendon in an animal model: a histologic and biomechanical study. J Shoulder Elb Surg 9(2):79–84

    Google Scholar 

  • Spanoudes K, Gaspar D, Pandit A, Zeugolis DI (2014) The biophysical, biochemical, and biological toolbox for tenogenic phenotype maintenance in vitro. Trends Biotechnol 32(9):474–482

    Google Scholar 

  • Stanco D, Caprara C, Ciardelli G, Mariotta L, Gola M, Minonzio G, Soldati G (2019) Tenogenic differentiation protocol in xenogenic-free media enhances tendon-related marker expression in ASCs. PLoS One 14(2)

    Google Scholar 

  • Subramony SD, Dargis BR, Castillo M, Azeloglu EU, Tracey MS, Su A, Lu HH (2013) The guidance of stem cell differentiation by substrate alignment and mechanical stimulation. Biomaterials 34(8):1942–1953

    Google Scholar 

  • Theisen C, Fuchs-Winkelmann S, Knappstein K, Efe T, Schmitt J, Paletta JRJ, Schofer MD (2010) Influence of nanofibers on growth and gene expression of human tendon derived fibroblast. Biomed Eng Online 9:1–12

    Google Scholar 

  • Tomás AR, Gonçalves AI, Paz E, Freitas PP, Domingues RMA, Gomes ME (2019) Magneto-mechanical actuation of magnetic responsive fibrous scaffolds boosts Tenogenesis of human adipose stem cells. Nanoscale

    Google Scholar 

  • Tong WY, Shen W, Yeung CW, Zhao Y, Cheng SH, Chu PK, Chan D, Chan GC, Cheung KM, Yeung KW, Lam YW (2012) Functional replication of the tendon tissue microenvironment by a bioimprinted substrate and the support of tenocytic differentiation of mesenchymal stem cells. Biomaterials 33(31):7686–7698

    Google Scholar 

  • Vining KH, Mooney DJ (2017) Mechanical forces direct stem cell behaviour in development and regeneration. Nat Rev Mol Cell Biol 18(12):728–742

    Google Scholar 

  • Wakefield LM, Hill CS (2013) Beyond TGF beta: roles of other TGF beta superfamily members in cancer. Nat Rev Cancer 13(5):328–341

    Google Scholar 

  • Wang JH-C (2006) Mechanobiology of tendon. J Biomech 39(9):1563–1582

    Google Scholar 

  • Wang JHC, Guo QP, Li B (2012) Tendon biomechanics and Mechanobiology-A Minireview of basic concepts and recent advancements. J Hand Ther 25(2):133–140

    Google Scholar 

  • Wang T, Gardiner BS, Lin Z, Rubenson J, Kirk TB, Wang A, Xu J, Smith DW, Lloyd DG, Zheng MH (2013) Bioreactor Design for Tendon/ligament engineering. Tissue Eng Part B Rev 19(2):133–146

    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(51):53331–53337

    Google Scholar 

  • Willett TL, Labow RS, Avery NC, Lee JM (2007) Increased proteolysis of collagen in an in vitro tensile overload tendon model. Ann Biomed Eng 35(11):1961–1972

    Google Scholar 

  • Woo SLY, Hildebrand K, Watanabe N, Fenwick JA, Papageorgiou CD, Wang JHC (1999) Tissue engineering of ligament and tendon healing. Clin Orthop Relat Res 367:S312–S323

    Google Scholar 

  • Wrighton KH, Lin X, Feng XH (2009) Phospho-control of TGF-beta superfamily signaling. Cell Res 19(1):8–20

    Google Scholar 

  • Wu S, Wang Y, Streubel PN, Duan B (2017) Living nanofiber yarn-based woven biotextiles for tendon tissue engineering using cell tri-culture and mechanical stimulation. Acta Biomater 62:102–115

    Google Scholar 

  • Xie J, Li X, Lipner J, Manning CN, Schwartz AG, Thomopoulos S, Xia Y (2010) “Aligned-to-random” nanofiber scaffolds for mimicking the structure of the tendon-to-bone insertion site. Nanoscale 2(6):923–923

    Google Scholar 

  • Yang G, Rothrauff BB, Lin H, Gottardi R, Alexander PG, Tuan RS (2013) Enhancement of tenogenic differentiation of human adipose stem cells by tendon-derived extracellular matrix. Biomaterials 34:9295–9306

    Google Scholar 

  • Yang G, Lin H, Rothrauff BB, Yu S, Tuan RS (2016) Multilayered polycaprolactone/gelatin fiber-hydrogel composite for tendon tissue engineering. Acta Biomater 35:68–76

    Google Scholar 

  • Yang G, Rothrauff BB, Lin H, Yu S, Tuan RS (2017) Tendon-derived extracellular matrix enhances transforming growth factor-β3-induced Tenogenic differentiation of human adipose-derived stem cells. Tissue Eng A 23(3–4):166–176

    Google Scholar 

  • Yin Z, Guo J, Wu TY, Chen X, Xu LL, Lin SE, Sun YX, Chan KM, Ouyang H, Li G (2016) Stepwise differentiation of mesenchymal stem cells augments tendon-like tissue formation and defect repair in vivo. Stem Cells Transl Med 5(8):1106–1116

    Google Scholar 

  • Younesi M, Islam A, Kishore V, Anderson JM, Akkus O (2014) Tenogenic induction of human MSCs by Anisotropically aligned collagen biotextiles. Adv Funct Mater 24(36):5762–5770

    Google Scholar 

  • Yu H, Lim KP, Xiong S, Tan LP, Shim W (2013) Functional morphometric analysis in cellular behaviors: shape and size matter. Adv Healthc Mater 2(9):1188–1197

    Google Scholar 

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

    Google Scholar 

  • Zhang C, Yuan H, Liu H, Chen X, Lu P, Zhu T, Yang L, Yin Z, Heng BC, Zhang Y, Ouyang H (2015) Well-aligned chitosan-based ultrafine fibers committed Teno-lineage differentiation of human induced pluripotent stem cells for Achilles tendon regeneration. Biomaterials 53:716–730

    Google Scholar 

  • Zhang YJ, Chen X, Li G, Chan KM, Heng BC, Yin Z, Ouyang HW (2018a) Concise review: stem cell fate guided by bioactive molecules for tendon regeneration. Stem Cells Transl Med 7(5):404–414

    Google Scholar 

  • Zhang H, Liu M-F, Liu R-C, Shen W-L, Yin Z, Chen X (2018b) Physical microenvironment-based inducible scaffold for stem cell differentiation and tendon regeneration. Tissue Eng Part B Rev 24(6):443–453

    Google Scholar 

  • Zhang C, Wang X, Zhang E, Yang L, Yuan H, Tu W, Zhang H, Yin Z, Shen W, Chen X, Zhang Y, Ouyang H (2018c) An epigenetic bioactive composite scaffold with well-aligned nanofibers for functional tendon tissue engineering. Acta Biomater 66:141–156

    Google Scholar 

  • Zhao X, Jiang SC, Liu S, Chen S, Lin ZY, Pan GQ, He F, Li FF, Fan CY, Cui WG (2015) Optimization of intrinsic and extrinsic tendon healing through controllable water-soluble mitomycin-C release from electrospun fibers by mediating adhesion-related gene expression. Biomaterials 61:61–74

    Google Scholar 

  • Zheng Z, Ran J, Chen W, Hu Y, Zhu T, Chen X, Yin Z, Heng BC, Feng G, Le H, Tang C, Huang J, Chen Y, Zhou Y, Dominique P, Shen W, Ouyang HW (2017) Alignment of collagen fiber in knitted silk scaffold for functional massive rotator cuff repair. Acta Biomater 51:317–329

    Google Scholar 

Download references

Acknowledgments

Authors acknowledge the project “Accelerating tissue engineering and personalized medicine discoveries by the integration of key enabling nanotechnologies, marine-derived biomaterials and stem cells,” supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).

Authors acknowledge the H2020 Achilles Twinning Project No. 810850, and also the European Research Council CoG MagTendon No. 772817, and the FCT Project MagTT PTDC/CTM-CTM/29930/2017 (POCI-01-0145-FEDER-29930).

Author information

Authors and Affiliations

  1. 3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Barco/Guimarães, Portugal

    Ana I. Gonçalves, Márcia T. Rodrigues, Ana M. Matos, Helena Almeida, Manuel Gómez-Florit, Rui M. A. Domingues & Manuela E. Gomes

  2. ICVS/3B’s–PT Government Associate Laboratory, Braga/Guimarães, Portugal

    Ana I. Gonçalves, Márcia T. Rodrigues, Ana M. Matos, Helena Almeida, Manuel Gómez-Florit, Rui M. A. Domingues & Manuela E. Gomes

Authors
  1. Ana I. Gonçalves
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Márcia T. Rodrigues
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ana M. Matos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Helena Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Manuel Gómez-Florit
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rui M. A. Domingues
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Manuela E. Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manuela E. Gomes .

Editor information

Editors and Affiliations

  1. Klinik für Urologie, NORD1 B200, Universitäts Spital, Zürich, Zürich, Switzerland

    Daniel Eberli

  2. Institute for Regenerative Medicine, Wake Forest University, Winston Salem, NC, USA

    Sang Jin Lee

  3. Inst of Tendon and Bone Regeneration, Paracelsus Medical University, Salzburg, Austria

    Andreas Traweger

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Gonçalves, A.I. et al. (2020). Multiscale Multifactorial Approaches for Engineering Tendon Substitutes. In: Eberli, D., Lee, S., Traweger, A. (eds) Organ Tissue Engineering. Reference Series in Biomedical Engineering(). Springer, Cham. https://doi.org/10.1007/978-3-030-18512-1_8-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-18512-1_8-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-18512-1

  • Online ISBN: 978-3-030-18512-1

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

Publish with us

Policies and ethics

Search

Navigation