Tissue engineering of flexor tendons addresses a challenge often faced by hand surgeons: the restoration of function and improvement of healing with a limited supply of donor tendons. Creating an engineered tendon construct is dependent upon understanding the normal healing mechanisms of the tendon and tendon sheath. The production of a tendon construct includes: creating a three-dimensional scaffold; seeding cells within the scaffold; encouraging cellular growth within the scaffold while maintaining a gliding surface; and finally ensuring mechanical strength. An effective construct incorporates these factors in its design, with the ultimate goal of creating tendon substitutes that are readily available to the reconstructive hand surgeon.
AbousleimanRIReyesYMcFetridgePSikavitsasV. Tendon tissue engineering using cell-seeded umbilical veins cultured in a mechanical stimulator. Tissue Eng Part A. 2009, 15: 787–95.
2.
AbrahamssonSOLundborgGLohmanderLS. Tendon healing in vivo. An experimental model. Scand J Plas Reconstr Surg Hand Surg. 1989, 23: 199–205.
3.
AngelidisIKThorfinnJConnollyIDLindseyDPhamHMChangJ. Tissue engineering of flexor tendons: the effect of a tissue bioreactor on adipoderived stem cell-seeded and fibroblast-seeded tendon constructs. J Hand Surg Am. 2010, 35: 1466–72.
4.
BranfordOAKlassBRGrobbelaarAORolfeKJ. The growth factors involved in flexor tendon repair and adhesion formation. J Hand Surg Eur. 2014, 39: 60–70.
CaliariSRRamirezMAHarleyBA. The development of collagen-GAG scaffold-membrane composites for tendon tissue engineering. Biomaterials. 2011, 32: 8990–8.
7.
ChenBWangBZhangWJZhouGCaoYLiuW. In vivo tendon engineering with skeletal muscle derived cells in a mouse model. Biomaterials. 2012, 33: 6086–97.
CostaMAWuCPhamBVChongAKPhamHMChangJ. Tissue engineering of flexor tendons: optimization of tenocyte proliferation using growth factor supplementation. Tissue Eng. 2006, 12: 1937–43.
10.
FarhatYMAl-MalikiAAChenT. Gene expression analysis of the pleiotropic effects of TGF-beta1 in an in vitro model of flexor tendon healing. PloS One. 2012, 7: e51411. DOI: 10.1371/journal.pone.0051411.
11.
FoxPMFarneboSLindseyDChangJSchmittTChangJ. Decellularized human tendon-bone grafts for composite flexor tendon reconstruction: A cadaveric model of initial mechanical properties. J Hand Surg Am. Epub ahead of print 19 September 2013. DOI: 10.1016/j.jhsa.2013.08.092.
12.
GalatzLMRothermichSYZaegelMSilvaMJHavliogluNThomopoulosS. Delayed repair of tendon to bone injuries leads to decreased biomechanical properties and bone loss. J Orthop Res. 2005, 23: 1441–7.
13.
GeninGMKentABirmanV. Functional grading of mineral and collagen in the attachment of tendon to bone. Biophys J. 2009, 97: 976–85.
14.
HagbergLTengbladAGerdinB. Elimination of exogenously injected sodium-hyaluronate from rabbit flexor tendon sheaths. J Orthop Res. 1991, 9: 792–7.
15.
HashimotoTSunYLAnKNAmadioPCZhaoC. The effect of tendon surface treatment on cell attachment for potential enhancement of tendon graft healing: an ex vivo model. Med Eng Phys. 2012, 34: 1387–93.
16.
HungLKFuSCLeeYWMokTYChanKM. Local vitamin-C injection reduced tendon adhesion in a chicken model of flexor digitorum profundus tendon injury. J Bone Joint Surg Am. 2013, 95: e41. DOI: 10.2106/JBJS.K.00988
17.
JamesRKesturuGBalianGChhabraAB. Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options. J Hand Surg Am. 2008, 33: 102–12.
18.
JayGDTorresJRRheeDK. Association between friction and wear in diarthrodial joints lacking lubricin. Arthritis Rheum. 2007, 56: 3662–9.
19.
JiangKWangZDuQYuJWangAXiongY. A new TGF-beta3 controlled-released chitosan scaffold for tissue engineering synovial sheath. J Biomed Mater Res A. Epub ahead of print 8 April 2013. DOI: 10.1002/jbm.a.34742.
20.
JorgensenHGMcLellanSDCrossanJFCurtisAS. Neutralisation of TGF beta or binding of VLA-4 to fibronectin prevents rat tendon adhesion following transection. Cytokine. 2005, 30: 195–202.
21.
KatzelEBWolenskiMLoiselleAE. Impact of Smad3 loss of function on scarring and adhesion formation during tendon healing. J Orthopaedic Res. 2011, 29: 684–93.
22.
KrygerGSChongAKCostaMPhamHBatesSJChangJ. A comparison of tenocytes and mesenchymal stem cells for use in flexor tendon tissue engineering. J Hand Surg Am. 2007, 32: 597–605.
23.
KulickMIBrazlowRSmithSHentzVR. Injectable ibuprofen: preliminary evaluation of its ability to decrease peritendinous adhesions. Ann Plast Surg. 1984, 13: 459–67.
LeversedgeFJZeloufDWilliamsCGelbermanRHSeilerJG. Flexor tendon grafting to the hand: an assessment of the intrasynovial donor tendon-A preliminary single-cohort study. J Hand Surg Am. 2000, 25: 721–30.
26.
LongoUGLambertiAPetrilloSMaffulliNDenaroV. Scaffolds in tendon tissue engineering. Stem Cells Int. Epub ahead of print 11 December 2011. DOI: 10.1155/2012/517165.
27.
ManningCNSchwartzAGLiuW. Controlled delivery of mesenchymal stem cells and growth factors using a nanofiber scaffold for tendon repair. Acta Biomater. 2013, 9: 6905–14.
28.
Moro-okaTMiuraHMawatariT. Mixture of hyaluronic acid and phospholipid prevents adhesion formation on the injured flexor tendon in rabbits. J Orth Res. 2000, 18: 835–40.
29.
MurphyKDMushkudianiIAKaoDLevesqueAYHawkinsHKGouldLJ. Successful incorporation of tissue-engineered porcine small-intestinal submucosa as substitute flexor tendon graft is mediated by elevated TGF-beta1 expression in the rabbit. J Hand Surg Am. 2008, 33: 1168–78.
30.
Newsham-WestRNicholsonHWaltonMMilburnP. Long-term morphology of a healing bone-tendon interface: a histological observation in the sheep model. J Anat. 2007, 210: 318–27.
31.
NiklasonLEGaoJAbbottWM. Functional arteries grown in vitro. Science. 1999, 284: 489–93.
32.
OmaeHZhaoCSunYLAnKNAmadioPC. Multilayer tendon slices seeded with bone marrow stromal cells: a novel composite for tendon engineering. J Orthop Res. 2009, 27: 937–42.
33.
OzturkAMYamAChinSIHeongTSHelvaciogluFTanA. Synovial cell culture and tissue engineering of a tendon synovial cell biomembrane. J Biomedical Mater Res A. 2008, 84: 1120–6.
34.
PridgenBCWoonCYKimM. Flexor tendon tissue engineering: acellularization of human flexor tendons with preservation of biomechanical properties and biocompatibility. Tissue Eng Part C Methods. 2011, 17: 819–28.
35.
RaghavanSSWoonCYKrausA. Human flexor tendon tissue engineering: decellularization of human flexor tendons reduces immunogenicity in vivo. Tissue Eng Part A. 2012a, 18: 796–805.
36.
RaghavanSSWoonCYKrausAMegerleKPhamHChangJ. Optimization of human tendon tissue engineering: synergistic effects of growth factors for use in tendon scaffold repopulation. Plas Reconstr Surg. 2012b, 129: 479–89.
37.
SaberSZhangAYKiSH. Flexor tendon tissue engineering: bioreactor cyclic strain increases construct strength. Tissue Eng Part A. 2010, 16: 2085–90.
38.
SavageR. The search for the ideal tendon repair in zone 2: strand number, anchor points and suture thickness. J Hand Surg Eur. 2014, 39: 20–29.
39.
SeilerJGChuCRAmielDWooSLGelbermanRH. The Marshall R. Urist Young Investigator Award. Autogenous flexor tendon grafts. Biologic mechanisms for incorporation. Clin Orthop Rel Res. 1997, 345: 239–47.
40.
SilvaMJThomopoulosSKusanoN. Early healing of flexor tendon insertion site injuries: Tunnel repair is mechanically and histologically inferior to surface repair in a canine model. J Orthop Res. 2006, 24: 990–1000.
41.
St OngeRWeissCDenlingerJLBalazsEA. A preliminary assessment of Na-hyaluronate injection into “no man’s land” for primary flexor tendon repair. Clin Orthop Rel Res. 1980, 146: 269–75.
42.
SunYBergerEJZhaoCJayGDAnKNAmadioPC. Expression and mapping of lubricin in canine flexor tendon. J Orthop Res. 2006, 24: 1861–8.
43.
SunYChenMYZhaoCAnKNAmadioPC. The effect of hyaluronidase, phospholipase, lipid solvent and trypsin on the lubrication of canine flexor digitorum profundus tendon. J Orthop Res. 2008, 26: 1225–9.
44.
TangJB. Outcomes and evaluation of flexor tendon repair. Hand Clin. 2013, 29: 251–9.
45.
ThomopoulosSGeninGMGalatzLM. The development and morphogenesis of the tendon-to-bone insertion – what development can teach us about healing. J Musculoskelet Neuronal Interact. 2010b, 10: 35–45.
46.
ThomopoulosSHarwoodFLSilvaMJAmielDGelbermanRH. Effect of several growth factors on canine flexor tendon fibroblast proliferation and collagen synthesis in vitro. J Hand Surg Am. 2005, 30: 441–7.
47.
ThomopoulosSKimHMDasR. The effects of exogenous basic fibroblast growth factor on intrasynovial flexor tendon healing in a canine model. J Bone Joint Surg Am. 2010a, 92: 2285–93.
48.
ThomopoulosSMarquezJPWeinbergerBBirmanVGeninGM. Collagen fiber orientation at the tendon to bone insertion and its influence on stress concentrations. J Biomech. 2006, 39: 1842–51.
49.
ThomopoulosSWilliamsGRGimbelJAFavataMSoslowskyLJ. Variation of biomechanical, structural, and compositional properties along the tendon to bone insertion site. J Orthop Res. 2003, 21: 413–9.
50.
ThorfinnJAngelidisIKGiglielloLPhamHMLindseyDChangJ. Bioreactor optimization of tissue engineered rabbit flexor tendons in vivo. J Hand Surg Eur. 2012, 37: 109–14.
51.
UchiyamaSAmadioPCCoertJHBerglundLJAnKN. Gliding resistance of extrasynovial and intrasynovial tendons through the A2 pulley. J Bone Joint Surg Am. 1997, 79: 219–24.
52.
UysalACMizunoH. Tendon regeneration and repair with adipose derived stem cells. Curr Stem Cell Res Ther. 2010, 5: 161–7.
VaquetteCSlimaniSKahnCJTranNRahouadjRWangX. A poly(lactic-co-glycolic acid) knitted scaffold for tendon tissue engineering: an in vitro and in vivo study. J Biomater Sci Polym Ed. 2010, 21: 1737–60.
55.
ViinikainenAGoranssonHHuovinenKKellomakiMTormalaPRokkanenP. The strength of the 6-strand modified Kessler repair performed with triple-stranded or triple-stranded bound suture in a porcine extensor tendon model: an ex vivo study. J Hand Surg Am. 2007, 32: 510–7.
56.
WooSLDebskiREZeminskiJAbramowitchSDSawSSFenwickJA. Injury and repair of ligaments and tendons. Ann Rev Biomed Eng. 2000, 2: 83–118.
57.
WoonCYFarneboSSchmittT. Human flexor tendon tissue engineering: revitalization of biostatic allograft scaffolds. Tissue Eng Part A. 2012, 18: 2406–17.
58.
WoonCYKrausARaghavanSS. Three-dimensional-construct bioreactor conditioning in human tendon tissue engineering. Tissue Eng Part A. 2011b, 17: 2561–72.
59.
WoonCYPridgenBCKrausABariSPhamHChangJ. Optimization of human tendon tissue engineering: peracetic acid oxidation for enhanced reseeding of acellularized intrasynovial tendon. Plast Reconstr Surg. 2011a, 127: 1107–17.
60.
XuLCaoDLiuWZhouGZhangWJCaoY. In vivo engineering of a functional tendon sheath in a hen model. Biomaterials. 2010, 31: 3894–902.
61.
YaoJWoonCYBehnA. The effect of suture coated with mesenchymal stem cells and bioactive substrate on tendon repair strength in a rat model. J Hand Surg Am. 2012, 37: 1639–45.
62.
YokoyaSMochizukiYNatsuKOmaeHNagataYOchiM. Rotator cuff regeneration using a bioabsorbable material with bone marrow-derived mesenchymal stem cells in a rabbit model. Am J Sports Med. 2012, 40: 1259–68.
63.
YoungRGButlerDLWeberWCaplanAIGordonSLFinkDJ. Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair. J Orthop Res. 1998, 16: 406–13.
64.
ZhangAYBatesSJMorrowEPhamHPhamBChangJ. Tissue-engineered intrasynovial tendons: optimization of acellularization and seeding. J Rehabil Res Dev. 2009, 46: 489–98.
