Smit Group – Mechanobiology of Development and Disease

Embryonic development essentially is a process of transport, deformation and growth and thus subjected to the laws of physics. Mechanical loading is also important for the maintenance of tissues (“use it or lose it”) and it is involved in the onset and progress of diseases like osteoarthritis and cancer. Our long-term goal is to obtain a better understanding of the role of mechanics in development and disease and to optimize treatment with the use of instructive biomaterials.

Contact: T.H. Smit (

Research overview

1. Development of the spine

The spine is the characteristic anatomical feature of vertebrates. It essentially is a segmented structure of bone and cartilage that replaces the chorda, the primitive axial structure defining the Chordata. The formation of the spine involves various elementary biological processes: migration, growth, condensation, segmentation, and mesenchymal-epithelial transition (MET) as well as epithelial-mesenchymal transition (EMT). These play a role in most developmental processes, but also in diseases like cancer and therefore need to be studied.

To observe the process of embryonic development, we built a filter paper sandwich culture for chick embryos which allows for micro-manipulations and wide-field time-lapse imaging (video1). We applied surplus axial mechanical strain which resulted in stretched somites and occasionally somite division (fig.1). Using a cellular Potts model, we were able to simulate this morphological reorganisation, including mesenchymal-epithelial transition (video2). Future research includes formation of the sclerotome around the notochord and the resegmentation of the embryonic axis into an array of condensations. We also investigate the embryonic origin of adolescent idiopathic scoliosis.

2. Onset and treatment of osteoarthritis

Osteo-arthritis is the end stage of articular cartilage degeneration, most often induced by mechanical overloading. Very similar processes occur in intervertebral disc degeneration, where mechanical shear stress on chondrocytes induce katabolic and inflammatory gene expressions, resulting in enzymes that break down the matrix and lead to further deterioration of the tissue. This interaction between mechanics and immunology results in a vicious process of degeneration, both in spine and articular cartilage (fig.2). We further study trauma-induced osteo-arthritis of the ankle joint and instability of the knee joint with degeneration.

The long-term goal of this research line is to stop and reverse the vicious process of degeneration. We do that with the help of hydrogels that can reduce mechanical stress to the affected cartilage and create an environment of hydrostatic pressure in which chondrocytes produce new healthy matrix. Spine, knee and ankle joint impose specific requirements on the gel to be successful in tissue regeneration. For clinical impact, there is a close collaboration with orthopedic surgeons and radiologists, as well as industry.

3. New implants for pelvic organ prolapse

Soft tissues like fascia, tendon, muscle and skin also suffer from mechanical overloading, resulting in a process of remodeling and repair. If the mechanical conditions are suboptimal, these tissues get in a situation of frustrated healing, resulting in scar formation and tissue contraction. One prominent example is pelvic organ prolapse, where large strains as a result of child delivery or obesity induce considerable damage to the pelvic floor. These tissues are under permanent mechanical loading due to the normal activities of daily life, like breathing, walking, coughing, laughing, etc. One goal of this research line is to understand the process of frustrated healing and see what mechanical loading conditions would be beneficial for tissue regeneration.

The long-term goal of this research line is to develop implants to provide temporary mechanical support, so that tissues can heal properly after trauma. For this purpose, we investigate the use of electrospun scaffolds, consisting of polymers with a fiber size between 10nm-100um (fig.3). These scaffolds not only provide mechanical support, but also serve as an instructive scaffold for fibroblasts and myoblasts to attach, proliferate, differentiate and produce extracellular matrix. Electrospun scaffolds are of interest also for retina repair (Bruch’s membrane), uterus repair after Caesarian delivery, burn wound healing, and periost flap for bone healing.

Video 1. Time-lapse of a developing chick embryo, showing the periodic formation of somites and the emergence of the beating heart. For details on the culture system see

Figure 1. Somites in a stretched chick embryo may reorganize into daughter somites (top row) involving strain-induced mesenchymal-epithelial transition.

Video 2: Computer simulation (cellular Potts model) of somite doubling under mechanical strain. The epithelial boundary is overstretched, thereby disconnecting the intercellular connections. The lateral sides of the disrupted cells subsequently induce MET in the mesenchymal core of the somite, which reorganizes to form new epithelial boundaries (model by Tahir and Merks).

Figure 2. Vicious circle of cartilage degeneration connecting mechanical loading to catabolic and inflammatory gene expressions of the cells, resulting in the degradation of extracellular matrix and subsequent change of mechanical loading.

Figure 3: cell seeded on an electrospun scaffold made of nylon, mimicking the sub-micron architecture of the extracellular matrix.


Coming soon

  1. Paul CPL, Smit TH, de Graaf M, Holewijn RM, Bisschop A, van de Ven PM, et al. (2018): Quantitative MRI in early intervertebral disc degeneration: T1rho correlates better than T2 and ADC with biomechanics, histology and matrixcontent. PLoS ONE 13(1): e0191442.
  2. Emanuel KS, van der Veen AJ, Rustenburg CM, Smit TH, Kingma I (accepted): Osmosis and viscoelasticity both contribute to time-dependent behaviour of the intervertebral disc under compressive load: a caprine in vitro study. J. Biomech.
  3. Beekmans SV, Emanuel KS, Smit TH, Iannuzzi D (2017): Minimally Invasive Micro-Indentation: mapping tissue mechanics at the tip of an 18G needle. Scient. Reports. 7(1):11364.
  4. Vashaghian M, Zaat SAJ, Smit TH, Roovers JP (2017): Biomimetic nanofiber implants for pelvic floor repair. Neurol. Urodyn.
  5. de Jong T, Bakker AD, Everts V, Smit TH (2017): The intricate anatomy of the periodontal ligament and its development: lessons for periodontal regeneration. J. Periodontal Res. 52(6):965-974.
  6. Vergroesen PPA, Emanuel KA, Peeters M, Kinma I, Smit TH (accepted): Are axial intervertebral disc biomechanics determined by osmosis? J. Biomechanics.
  7. van de Bunt F, Emanuel KS, Wijffels T, Kooren PN, Kingma I, Smit TH (2017): A novel physiological testing device to study knee biomechanics in vitro. Knee 24(4):718-725.
  8. Paul CPL, de Graaf M, Bisschop A, Holewijn RM, van de Ven PM, van Royen BJ, Mullender MG, Smit TH, Helder MN (2017): Static axial overloading primes lumbar caprine intervertebral discs for posterior herniation. PlosONE 12(4):e0174278.
  9. de Jong T, Oostendorp C, van Kuppevelt TH, Bakker AD, Smit TH (2017): Adipose-derived-stem-cell-seeded fibrin matrices for periodontal ligament engineering: the need for dynamic strain. J. Biomat Tiss Eng.7(12): 1303-1312.
  10. Teunissen M, van der Veen AJ, Smit TH, Tryfonidou MA, Meij BP (2017): A titanium cage as a stand-alone device restores biomechanical stability and disc height in the lumbosacral spine: a cadaveric study. Vet. J. 220:17-23.
  11. Crijns T, Stadhouder A, Smit TH (2017): Restrained differential growth: the initiating event of adolescent idiopathic scoliosis? Spine 42(12): E726-E732.
  12. Vashaghian M, Zandieh-Doulabi B, Roovers JP, Smit TH (2016): Electrospun matrices for pelvic floor repair: effect of fiber diameter on mechanical properties and cell behavior. Tiss Engg A 22 (23-24):1305-1316
  13. Schmitz M, Nelemans B, Smit TH (2016): A submerged filter paper sandwich for long-term ex ovo time-lapse imaging of early chick embryos. J Vis. Exp.
  14. Ghazanfari S, Khademhoseini A, Smit TH (2016): Mechanisms of lamellar collagen formation in connective tissues. Biomaterials 97: 74-84.
  15. Ruiz-Zapata AM, Kerkhof MH, Ghazanfari S, Zandieh-Doulabi B, Stoop R, Smit TH, Helder MN (2016): Vaginal fibroblastic cells from women with pelvic organ prolapse produce matrices with increased stiffness and collagen content. Sci. Rep. 6:22971.
  16. de Jong T, Weijers EM, Bakker AD, Koolwijk P, Smit TH (2016): Matrix remodeling and osteogenic differentiation of human adipose-derived stem cells increase with higher fibrin matrix stiffness. J. Biomat Tiss Eng. 6(9): 729-738
  17. Emanuel K, Kingma I, Helder MH, Smit TH (2016): Response to: ‘A dose–response relationship between severity of disc degeneration and intervertebral disc height in the lumbosacral spine’. Arthr. Res Ther. 18(1):41.
  18. Vashaghian M, Ruiz-Zapata AM, Kerkhof MH, Zandieh-Doulabi B, Werner A, Roovers JP, Smit TH (2017): Towards a new generation of pelvic floor implants with electrospun nanofibrous matrices: a feasibility study. Neurourology and Urodynamics 36(3):565-57.
  19. Fazaeli S, Ghazanfari S, Everts V, Smit TH, Koolstra JH (2016): The Contribution of Collagen Fibers to the Mechanical Compressive Properties of the Temporomandibular Joint Disc. Osteoarthritis & Cartilage 24: 1292-1301.
  20. Mader KT, Peeters M, Detiger SEL, Helder MN, Smit TH, Le Maitre C, Sammon C (2016): Investigation of intervertebral disc degeneration using multivariate FTIR spectroscopic imaging. Faraday Discussions 187:393-414.
  21. Vergroesen PPA, van der Veen AJ, Emanuel KS, van Dieën JH, Smit TH (2016.): The poro-elastic behaviour of the intervertebral disc: a new perspective on diurnal fluid flow. J. Biomechanics 49: 857–863.
  22. Detiger SEL, de Bakker JY, Emanuel K, Schmitz M, Vergroesen PPA, van der Veen AJ, Mazel C, Smit TH (2016): Translational challenges for the development of a novel nucleus pulposus substitute. J Biomat Appl. 30(7) 983–994.
  23. Peeters M, Detiger SEL, Karfeld-Sulzer LS, Smit TH, Yayon A, Weber FE, Helder MN (2015) BMP-2 and BMP-2/7 heterodimers conjugated to a fibrin-hyaluronic acid hydrogel in a large animal model of mild intervertebral disc degeneration. BioResearch Open Access 4.1: 398–406.
  24. Schutgens EM, Tryfonidou MA, Smit TH, Öner FC, Krouwels A, Ito K, Creemers LB (2015): Biomaterials for intervertebral disc regeneration; past performance and possible future strategies. European Cells and Materials 30: 210 – 231
  25. Klumpers DD, Mooney DJ, Smit TH (2015): From skeletal development to tissue engineering: lessons from the micromass assay. Tissue Eng B 21(5): 427-437.
  26. van Engelen SJ, Bisschop A, Smit TH, van Royen BJ, van Dieeën JH (2015): The effect of neighboring segments on the measurement of segmental stiffness in the intact lumbar spine. The Spine Journal 15: 1302–1309
  27. Emanuel KS, Vergroesen PPA, Peeters M, Holewijn RM, Kingma I, Smit TH (2015): Poro-elastic behaviour of the degenerating human intervertebral disc: a ten-day study in a loaded disc culture system. European Cells and Materials 29:330-341
  28. Klumpers DD, Smit TH, Mooney DJ (2015): The effect of growth-mimicking continuous strain on the early stages of skeletal development in micromass culture. PlosONE 10(4): e0124948.
  29. Vergroesen PPA, Kingma I, Emanuel KS, Hoogendoorn RJW, Welting TW, van Royen BJ, van Dieën JJ, Smit TH (2015): Mechanics and biology in intervertebral disc degeneration: a vicious circle. Osteoarthritis and Cartilage 23(7): 1057-1070.
  30. Detiger SEL, Helder MN, Smit TH, Hoogendoorn RJW (2015): Adverse effects of stromal vascular fraction during regenerative treatment of the intervertebral disc – observations in a goat model. Eur. Spine J. 24(9): 1992-2000.
  31. Vergroesen PPA, Bochyńska AI, Emanuel KS, Sharifi S, Kingma I, Grijpma DW, Smit TH (2015): A biodegradable glue for annulus closure: evaluation of strength and endurance. Spine 40(9): 622-628.
  32. Kroeze RJ, Smit TH, Vergroesen PP, Bank RA, Stoop R, van Rietbergen B, van Royen BJ, Helder MN (2015): Spinal fusion using adipose stem cells seeded on a radiolucent cage filler – a feasibility study of a single surgical procedure in goats. Eur Spine J. 24: 1031-1042.
  33. Castro APG, Paul CPL, Detiger SEL, Smit TH, van Royen BJ, Pimenta Claro JC, Mullender MG, Alves JL (2014): Long-Term Creep Behavior of the Intervertebral Disc: Comparison between Bioreactor Data and Numerical Results. Front. Bioengg Biotechn. 2: 56.
  34. Ruiz-Zapata AM, Kerkhof MH, Zandieh-Doulabi B, Brölmann HAM, Smit TH, Helder MN (2014): Functional characteristics of vaginal fibroblasts from premenopausal women with pelvic organ prolapse. Mol Hum Reprod. 20(11):1135-43.
  35. Detiger SEL, Holewijn RM, Hoogendoorn RJW, van Royen BJ, Helder MN, Berger FH, Kuijer JPA, Smit TH (2015): MRI T2* mapping correlates with biochemistry and histology in intervertebral disc degeneration in a large animal model. Eur. Spine J. 1935-43.
  36. Vergroesen PPA, van der Veen AJ, van Royen BJ, Kingma I, Smit TH (2014): Intradiscal pressure depends on recent loading and correlates with disc height and compressive stiffness. Eur. Spine J. 23(11):2359-68.
  37. Truskinovsky L, Vitali G, Smit TH (2014): A mechanical perspective on vertebral segmentation. Int J Eng Sci. 83: 124-137.
  38. Klumpers DD, Mao AS, Smit TH, Mooney DJ (2014): Linear patterning of mesenchymal condensations is modulated by geometric constraints. J.R. Soc. Interface 11(95): 20140215.
  39. van Engelen SJ, Bisschop A, Smit TH, van Royen BJ, van Dieën JH (2014): The effect of neighboring segments on the measurement of segmental stiffness in the intact lumbar spine. Spine J. 15(6):1302-9.
  40. Blaauboer ME, Boeijen FR, Emson CL, Turner SM, Zandieh-Doulabi B, Hanemaaijer R,  Smit TH, Stoop R, Everts V (2014): Extracellular matrix proteins: a positive feedback loop in lung fibrosis? Matrix Biology 34:170-8.
  41. Kroeze RJ, van der Veen AJ, van Royen BJ, Bank RA, Helder MN, Smit TH (2013): Relation between radiological assessment and biomechanical stability of lumbar interbody fusion in a large animal model. Eur Spine J 22:2731–2739.
  42. Klumpers DD, Zhao X, Mooney DJ, Smit TH (2013): Cell mediated contraction in 3D cell-matrix constructs leads to spatially regulated osteogenic differentiation. Integr Biol (Camb). 2013 Aug 19;5(9):1174-83.
  43. Jurgens WJ, Kroeze RJ, Zandieh-Doulabi B, van Dijk A, Renders GA, Smit TH, van Milligen FJ, Ritt MJ, Helder MN (2013): One-step surgical procedure for the treatment of osteochondral defects with adipose-derived stem cells in a caprine knee defect: a pilot study. Biores Open Access. 2013 Aug;2(4):315-25.
  44. Paul CP, Schoorl T, Zuiderbaan HA, Zandieh Doulabi B, van der Veen AJ, van de Ven PM, Smit TH, van Royen BJ, Helder MN, Mullender MG (2013): Dynamic and static overloading induce early degenerative processes in caprine lumbar intervertebral discs. PLoS One. 2013 Apr 30;8(4): e62411.
  45. Ruiz-Zapata RM, Kerkhof MH, Zandieh-Doulabi B, Brölmann HAM, Smit TH, Helder MH (2013): Fibroblasts from women with pelvic organ prolapse show differential mechano-responses depending on surface substrates. Int. Urogyn. J. 24: 1567-1575.
  46. Detiger SE, Hoogendoorn RJ, van der Veen AJ, van Royen BJ, Helder MN, Koenderink GH, Smit TH (2013): Biomechanical and rheological characterization of mild intervertebral disc degeneration in a large animal model. J Orthop Res 31(5):703-9.
  47. Söntjens SHM, Engels TAP, Smit TH, Govaert LE (2012): Time-dependent failure of amorphous poly-D,L-lactide: influence of molecular weight. J. Mech. Beh. Biomed. Mat. 13:69-77.
  48. Paul CP, Zuiderbaan HA, Zandieh Doulabi B, van der Veen AJ, van de Ven PM, Smit TH, Helder MN, van Royen BJ, Mullender MG (2012): Simulated-physiological loading conditions preserve biological and mechanical properties of caprine lumbar intervertebral discs in ex vivo culture. PLoS One. 2012;7(3):e33147.
  49. Bron JL, Mulder HW, Vonk LA, Doulabi BZ, Oudhoff MJ, Smit TH (2012): Migration of intervertebral disc cells into dense collagen scaffolds intended of functional replacement. J. Mater Sci Mater Med. 23(3):813-21.
  50. Kraan GA, Smit TH, Hoogland PV (2011): Extraforaminal ligaments of the cervical spinal nerves in humans. Spine J 11(12): 1128-34.
  51. Smolders LA, Bergknut N, Kingma I, Van der Veen AJ, Smit TH, Koole LH, Hazewinkel HA, Meij BP (2011): Biomechanical evaluation of a novel nucleus pulposus prosthesis in canine cadaveric spines. Veter. J. 192(2):199-205.
  52. van Engelen SJPM, van der Veen AJ, de Boer A, Ellenbroek MHM, Smit TH, van Royen BJ, van Dieën JH (2011): The feasibility of modal testing for measurement of the dynamic characteristics of goat vertebral motion segments. J. Biomech. 44(8):1478-83.
  53. Bron JL, Vonk LA, Smit TH, Koenderink GH (2011): Engineering Alginate for Intervertebral Disc Repair. J. Mech. Beh. Biomed. Mat. 4(7):1196-205.
  54. Smit TH, van Tunen MSLM, van der Veen AJ, Kingma I, van Dieën JH (2011): Quantifying intervertebral disc mechanics: new definition of the neutral zone. BMC Musculoskeletal Disorders 12:38.
  55. Vergroesen PP, Kroeze RJ, Helder MN, Smit TH (2011): The use of Poly(L-Lactide-co-Caprolactone) as a scaffold for adipose stem cells in bone tissue engineering: application in a spinal fusion model. Macromol. Biosc. 11(6):722-30.
  56. Blaauboer ME, Smit TH, Hanemaaier R, Stoop R, Everts V (2011): Cyclic Mechanical Stretch Reduces Myofibroblast Differentiation of Primary Lung Fibroblasts. Biochem Biophys Res Commun. 404(1):23-7.
  57. Jiya TU, Smit TH, van Royen BJ, Mullender M (2010): Posterior lumbar interbody fusion using non resorbable poly-ether-ether-ketone versus resorbable poly-L-lactide-co-D,L-lactide fusion devices. Clinical outcome at a minimum of 2 years follow up. Eur. Spine J. 20(4):618-22.
  58. Bron JL, van Royen BJ, van der Veen AJ, Helder M, Smit TH (2010): Biomechanical and In Vivo Evaluation of Experimental Closure Devices of the Annulus Fibrosus Designed for a Goat Nucleus Replacement Model. Eur. Spine J. 19(8): 1347-1355.
  59. Berendsen AD, Smit TH, Schoenmaker T, Walboomers XF, Harris SE, Everts V, Bronckers ALJJ (2010): Inorganic Phosphate Stimulates DMP1 Expression in Human Periodontal Ligament Fibroblasts Embedded in Three-Dimensional Collagen Gels. Cells Tissues Organs 192(2):116-24.
  60. Kroeze RJ, Helder MN, Roos WH, Wuite GJ, Bank RA, Smit TH (2010): The effect of ethylene oxide, glow discharge and electron beam on the surface characteristics of poly(l-lactide-co-caprolactone) and the corresponding cellular response of adipose stem cells. Acta Biomater. 2010 Jun;6(6):2060-5.
  61. Smit TH, Engels TAP, Söntjens SHM, Govaert LE (2010): Time-dependent failure in load-bearing polymers: a potential hazard in structural applications of polylactides. J. Mater Sci. Mater Med. 21(3):871-8.
  62. Kraan GA, Smit TH, Hoogland PVJM, Snijders CJ (2010): Lumbar extraforaminal ligaments act as a traction relief and prevent spinal nerve compression. Clinical Biomechanics 25(1): 10-5.
  63. Engels TAP, Söntjens SHM, Smit TH, Govaert LE (2010): Time-dependent failure of amorphous polylactides in static loading conditions. J Mater Sci Mater Med 21(1):89-97.
  64. Berendsen AD, Smit TH, Walboomers XF, Everts V, Jansen JA, Bronckers (2009): Three-Dimensional Loading Model for Periodontal Ligament Regeneration in vitro. Tissue Eng Part C Methods 15(4): 561-70.
  65. Kroeze RJ, Helder M, Govaert LE, Smit TH (2009): Biodegradable polymers in bone tissue engineering. Materials 2009, 2, 833-856
  66. Jiya TU, Smit TH, Deddens J, Mullender MG (2009): Posterior lumbar interbody fusion using non resorbable poly-ether-ether-ketone versus resorbable poly-L-lactide-co-D,L-lactide fusion device. A prospective randomized study to assess fusion and clinical outcome. Spine 34: 233-237.
  67. Bacabac RM, Van Loon JWA, Smit TH, Klein Nulend J (2009): Noise enhances the rapid nitric oxide production by bone cells in response to fluid shear stress. Technology and Health Care 17(1): 57-65.
  68. Van Hove RP, Nolte PA, Vatsa A, Semeins CM, Salmon PL, Smit TH, Klein Nulend J (2009): Difference in osteocyte morphology in osteoporotic, osteopetrotic and osteoarthitic bone – is there a role for mechanosensing? Bone 45(2): 321-329.
  69. Breuls RGM, Klumpers DD, Everts V, Smit TH (2009): Collagen Type V Modulates Fibroblast Behavior Dependent on Substrate Stiffness. Biochem Biophys Res Commun. 6;380(2):425-9.
  70. Bron JL, Helder MN, Meisel HJ, Van Royen BJ, Smit TH (2009): Repair, regenerative and supportive therapies of the annulus fibrosus: achievements and challenges. Eur. Spine J. 18(3): 301-13.
  71. Bron JL, Koenderink G, Everts V, Smit TH (2009.): Rheological Characterization of the Nucleus Pulposus and Dense Collagen Scaffolds intended for Functional Replacement. J Orthop Res. 2009 May;27(5):620-6.
  72. Krijnen MR, Smit TH, Everts V, and Wuisman PIJM (2009): PLDLA mesh and 60/40 biphasic calcium phosphate in iliac crest regeneration in the goat. J Biomed Mater Res B Appl Biomater. 89(1):9-17.
  73. Van Haaren EH, van der Zwaard BC, van der Veen AJ, Heyligers IC, Wuisman PIJM, and Smit TH (2008): Effect of long-term preservation on mechanical properties of bone. Acta Orthopaedica 79(5):708-16.
  74. Breuls RGM, Jiya TU, Smit TH (2008): Scaffold Stiffness Influences Basic Cell Behavior: Opportunities for Skeletal Tissue Engineering. Open Orthop. J. 2: 103-109.
  75. Vatsa A, Breuls RG, Semeins CM, Salmon PL, Smit TH, Klein Nulend J (2008): Osteocyte morphology in fibula and calvaria – is there a role for mechanosensing? Bone 43(3):452-8.
  76. Uffen MP, Krijnen MR, Hoogendoorn RJW, Strijkers GJ, Everts V, Wuisman PIJM, and Smit TH (2008): Tissue identification with micro-Magnetic Resonance Imaging: an ex-vivo goat study of spinal fusion. Eur. Spine. J. 17: 1006-1011.
  77. Hoogendoorn RJW, Helder MN, Wuisman PIJM, Bank RA, Everts V, Smit TH (2008): Adjacent Segment Degeneration: observations in a Goat Spinal Fusion Study.  Spine 33(12): 1337-1343.
  78. Hoogendoorn RJW, Helder MN, Kroeze RJ, Smit TH, Wuisman PIJM (2008): Reproducible long term disc degeneration in a large animal model. Spine 33(9): 949-954.
  79. Bacabac RG, Mizuno D, Vatsa A, Schmidt CF, MacKintosh FC, Klein-Nulend J, Smit TH, (2008): Round versus flat: bone cell morphology, elasticity, and mechanosensing. J. Biomech. 41(7):1590-8. Erratum in: J Biomech. 41(12):2786
  80. Van der Veen AJ, Mullender MG, Kingma I, Van Dieen JH, Smit TH (2008): Contribution of vertebral bodies, endplates, and intervertebral discs to the compression creep of spinal motion segments. J. Biomech. 41(6):1260-8.
  81. Vatsa A, Semeins CM, Smit TH, Klein Nulend J (2008): Paxillin localisation in osteocytes-Is it determined by the direction of loading? Biochem Biophys Res Commun. 377(4):1019-24.
  82. Pigge RR, Scheerder FJ, Smit TH, Mullender MG, Van Royen BJ (2008): Effectiveness of pre-operative planning in the restoration of balance and view in ankylosing spondylitis. Neurosurg. Focus 24 (1): E7.
  83. Smit TH, Engels TAP, Wuisman PI, Govaert LE (2008): Time-dependent mechanical strength of 70/30 poly(L,DL-lactide): shedding light on the premature failure of degradable spinal cages. Spine 33(1):14-8.
  84. Kouwenhoven JWM, Smit TH, Van der Veen AJ, Kingma I, van Dieen J, Castelein RM (2007): Effects of dorsal versus ventral shear loads on the rotational stability of the thoracic spine. Spine.32(23):2545-50.
  85. Hoogendoorn RJW, Wuisman PIJM, Smit TH, Everts V, Helder MN (2007): Experimental intervertebral disc degeneration induced by chondroitinase ABC in the goat. Spine 32(17):1816-25.
  86. Vatsa A, Smit TH, Klein Nulend J (2007): Extracellular NO signalling from a mechanically stimulated osteocyte. J. Biomech. 40 Suppl1: S89-S95.
  87. Berendsen A, Smit TH, Hoeben KA, Walboomers XF, Bronckers AJ, Everts V (2007): Alkaline phosphatase-induced mineral deposition to anchor collagen fibrils to a solid surface. Biomaterials. 2007 Aug;28(24):3530-6.
  88. Van Royen BJ, Scheerder FJ, Jansen E, Smit TH (2007): ASKyphoplan: a program for deformity planning in ankylosing spondylitis. Eur. Spine J. 2007 Apr.18
  89. Smit TH, Thomas KA, Hoogendoorn RJW, Strijkers GJ, Helder MN, Wuisman PI (2007): Sterilization and strength of 70/30 polylactide cages: e-beam vs. ethylene oxide. Spine 32(7): 742-747.
  90. van Laar W, Meester RJ, Smit TH and van Royen BJ. (2007): A biomechanical analysis of the self-retaining pedicle hook device in posterior spinal fixation. Eur Spine J. 16: 1209-14.
  91. Van der Veen AJ, Van Dieën J, Nadort A, Stam B, and Smit TH (2007): Intervertebral disc recovery after dynamic or static loading in vitro: is there a role for the endplate? J Biomech 40(10):2230-5
  92. Bacabac RG, Van Loon JJW, De Blieck-Hoogervorst J, Semeins CM, Zandieh-Dulabi B, Helder MN, Smit TH, Klein Nulend J: Microgravity and bone cell mechanosensitivity: FLOW experiment during the DELTA mission.  Microgravity Science and Technology 2007 19(5-6): 133-137
  93. Mullender MG, Krijnen MR, Helder MN, Smit TH, Everts V, Wuisman PI (2007): Lumbar Body Fusion with a Bioresorbable Cage in a Goat Model is Delayed by the Use of a Carboxymethylcellulose-Stabilized Collagenous RhOP-1 Device. J. Orthop. Res. 25(1):132-41
  94. Smit TH, Krijnen MR, Van Dijk M, Wuisman PIJM (2006): Application of polylactides in spinal cages: studies in a goat model. J Mater Sci Mater Med. 17(12):1237-44.
  95. Vatsa A, Mizuno D, Smit TH, Schmidt CF, MacKintosh FC, Klein Nulend J (2006): Bio-imaging of intracellular nitric oxide production in single bone cells after mechanical stimulation. J Bone Miner Res.21(11):1722-8
  96. Berendsen A, Bronckers AJ, Smit TH, Walboomers XF, Everts V (2006): Collagen type V enhances matrix contraction by human periodontal ligament fibroblasts seeded in 3D collagen gels. Matrix Biology 25(8):515-22
  97. Krijnen MR, Valstar ER, Smit TH, Wuisman PI (2006): Does bioresorbable cage material influence segment stability in spinal interbody fusion? Clin. Orthop. Rel. res. 448: 33-38
  98. Krijnen MR, Mensch D, Van Dieën J, Wuisman PIJM, Smit TH (2006): Primary spinal segment stability with a stand-alone cage – in vitro evaluation of a successful goat model. Acta Orthop 77(3):454-61
  99. Krijnen MR, Mullender MG, Smit TH, Everts V, Wuisman PIJM (2006): Radiographic, histologic and chemical evaluation of bioresorbable 70/30 poly (L-D,L-lactide) interbody fusion cages in a goat model. Spine 31(14):1559-67
  100. Bacabac RG, Smit TH, Van Loon JWA, Zandieh Doulabi B, Helder MN, Klein Nulend J: (2006) Bone cell responses to high-frequency vibration stress: does the nucleus oscillate within the cytoplasm?   FASEB J  20(7):858-64.
  101. Van Schoor NM, Van der Veen AJ, Schaap L, Smit TH, Lips P (2006): Biomechanical comparison of ten different hip protectors. Bone 39(2):401-7.
  102. Wuisman PIJM, Smit TH (2006): Bioresorbable polymers: heading for a new generation of spinal cages. Eur. Spine J.2006 Feb;15(2):133-48.
  103. Van Royen BJ, Kastelijns RCA, Noske DP, Öner FC, Smit TH (2006.): Transpedicular wedge resection osteotomy of a kyphotic Anderson lesion complicated ankylosing spondylitis. Eur Spine J. 15(2):246-52.
  104. Van der Veen AJ, Mullender M, Smit TH, Kingma I, Van Dieën J (2005): Flow related mechanics of the intervertebral disc: the validity of an in vitro model. Spine 30: E534-539.
  105. Van Royen BJ. Smit TH (2005): Indikation und Planung von Kolumnotomien bei Spondylitis ankylosans Arthritis + Rheuma 25: 189-193
  106. Klein-Nulend J, Vatsa A, Bacabac RG, Tan SD, Smit TH (2005): The role of osteocytes in bone mechanotransduction. Curr. Opinions Orthop. 16: 316-324
  107. Wuisman PI, Krijnen MR, Helder MN, Smit TH (2005): Bioabsorbable interbody cages in a sheep cervical spine fusion model. Spine 30(17):2005-6.
  108. Castelein RM, Van Dieën J, Smit TH (2005): Could dorsal shear forces contribute to Adolescent Idiopathic Scoliosis? Med. Hypoth. 65: 501-508.
  109. Klein Nulend J, Bacabac RG, Vatsa A, Tan D, Smit TH, Van Loon J (2005): Modulation of gene expression in bone cells during strain-adapted bone remodelling. J. Grav. Physiol.12: P225-P228
  110. Faber C, Hoogendoorn RJ, Lyaruu DM, Stallmann HP, van Marle J, Van Nieuw Amerongen A, Smit TH, Wuisman PI (2005): The effect of antimicrobial peptide, Dhvar-5, on gentamicin release from a polymethyl methacrylate bone cement. Biomaterials 26: 5717-5726.
  111. Van Dijk M, Van Diest PJ, Smit TH, Berkhof H, Burger EH, Wuisman PIJM (2005): Long-term tissue reaction to poly-L-lactic acid cages for lumbar interbody fusion – A 4-year follow-up study in goats. J Long Term Eff Med Implants.15(2):125-38.
  112. Van Haaren EH, Smit TH, Phipps K, Wuisman PI, Blunn G, Heyligers IC (2005): Tricalcium-phosphate and hydroxyapatite bone-graft extender for use in impaction grafting revision surgery. An in vitro study on human femora. J Bone Joint Surg Br. 87(2):267-71.
  113. Van Haaren EH, Smit TH, Van der Veen AJ, Wuisman PIJM, Heyligers IC (2005): A Bioresorbable Molding Mesh for Impaction Grafting Revision Hip Surgery. Clin Orthop Relat Res. 432:167-73.
  114. Bacabac RG, Smit TH, Mullender MG, Van Loon JJ, Klein-Nulend J (2005) Initial stress-kick is required for fluid shear stress-induced rate dependent activation of bone cells. Ann Biomed Eng. 33(1):104-10.
  115. Bacabac RG, Smit TH, Cowin SC, Heethaar RM, Klein Nulend J (2005): Dynamic shear stress in parallel-plate flow chambers. J. Biomech. 38: 159-167.
  116. Van Loon JJWA, Folgering EHTE, Bouten CVC, Veldhuijzen JP, Smit TH (2004.): Centrifuges and inertial shear forces. J. Grav. Physiol. 11: 29-38.
  117. Tunc DC, van Dijk M, Smit T, Higham P, Burger E, Wuisman P. (2004): Three-year follow-up of bioabsorbable PLLA cages for lumbar interbody fusion: in vitro and in vivo degradation., Adv Exp Med Biol.553:243-55.
  118. Van Haaren EH, Smit TH, Phipps K, Wuisman PI, Heyligers IC (2004): Tricalcium-phosphate/hydroxyapatite bone graft extender for use in impaction grafting revision surgery – an in vitro study in human femora.  Bioceramics 16: 667-670.
  119. Huyghe J.M.R.J. and Smit TH (2004): Comment les cellules de l’os ressentent-elles une contrainte mecanique? Arch. Physiol.Bioch. 112(suppl) 48-50.
  120. Krijnen MR, Smit TH, Strijkers GJ, Nicolay K, Pouwels PJW, Wuisman PIJM (2004): The use of high-resolution magnetic resonance imaging for monitoring interbody fusion and bioresorbable cages – an ex vivo pilot study. Neurosurgical Focus 16(3) E3
  121. Bacabac RG, Smit TH,  Dijcks S, Van Loon JJWA, Klein-Nulend J (2004): Nitric Oxide Production by Bone Cells is Fluid Shear Stress Rate Dependent. Biochem. Biophys. Res. Comm. Vol 315/4 pp 823-829
  122. Burger E.H., Klein-Nulend J., Smit T.H. (2003): Strain-derived canalicular fluid flow regulates osteoclast activity in a remodelling osteon – a proposal. J Biomech. 36(10):1453-9.
  123. Smit TH, Mueller R, Van Dijk M, Wuisman PIJM (2003) Changes in bone architecture during spinal fusion: three years follow-up and the effect of cage stiffness. Spine. 2003 Aug 15;28(16):1802-1808.
  124. Van Loon JJWA, Folgering EHTE, Bouten CVC, Veldhuijzen JP, Smit TH (2003): Inertial shear forces and the use of centrifuges in gravity research. What is the proper control? ASME JBE. 125: 342-346.
  125. Van Dijk M, Smit TH, Arnoe M, Burger EH, Wuisman PIJM (2003.) The Use of Poly (L-Lactic Acid) in Lumbar Interbody Cages – Design and Biomechanical Evaluation In Vitro. Eur Spine J. 12:34-40.
  126. Van Dijk M, Smit TH, Burger EH, Wuisman PIJM (2002): Bioabsorbable Poly-L-Lactic Acid Cages for Lumbar Interbody Fusion: Three-Year Follow-up Radiographic, Histologic, and Histomorphometric Analysis in Goats. Spine 27: 2706-14
  127. Wuisman PIJM, Van Dijk M, Smit TH (2002.) Resorbable cages for spinal fusion: an experimental goat model. J Neurosurg. 97(4 Suppl):433-439.
  128. Van Dijk M, Tunc DC, Smit TH, Higham P, Burger EH, Wuisman PIJM (2002) In vitro and in vivo degradation of bioabsorbable PLLA spinal fusion cages. J Biomed Mater Res. 63(6):752-9.
  129. Smit TH, Burger EH, Huyghe JM (2002.): A case for strain-induced fluid flow as a regulator of BMU-coupling and osteonal alignment. J Bone Miner Res. 11 :2021-2029.
  130. Wuisman PIJM, Van Dijk M, Smit TH (2002.) Resorbable cages for spinal fusion: an experimental goat model. Orthopedics 25(10 Suppl):s1141-8.
  131. Van Loon JJWA, Folgering EHTE, Bouten CVC, Veldhuijzen JP, Smit TH (2002): Inertial shear force and the impact on facilities for the International Space Station.  J Gravit Physiol. 9(1):P359-60.
  132. Van Dijk M, Smit TH, Burger EH, Wuisman PIJM (2002): Bone histomorphometric evaluation of a clinically fused titanium tumour cage in a child. Eur Spine J. 5: 507-511.
  133. Smit TH, Huyghe JM and Cowin SC (2002): A two-level poroelastic model of cortical bone: estimation of the linear isotropic parameters. J. Biomech. 35: 829-836.
  134. Van Dijk M, Smit TH, Sugihara S, Burger EH, Wuisman PIJM (2002.) The Effect of Cage Stiffness on the Rate of Lumbar Interbody Fusion. Spine 27: 682-688.
  135. Smit TH (2002): The use of a quadruped as an in vivo model for the study of the spine – biomechanical considerations. Eur. Spine J. 11: 137-144.
  136. Van Dijk M, Smit TH, Jiya TU and Wuisman PIJM (2001): Polyurethane real-size models used in planning complex spinal surgery. Spine 26(17):1920-6.
  137. Selles RW, Wagenaar RC, Smit TH and Wuisman PIJM (2001): Disorders in trunk rotation during walking in patients with low back pain: a dynamical systems approach. Clin. Biomech.16: 175-181.
  138. Royen BJ van, Gast A de and Smit TH (2000): Deformity planning for sagittal plane corrective osteotomies of the spine in ankylosing spondylitis. Eur. Spine 9(6): 492-498
  139. Smit TH and Burger EH (2000): Is BMU-coupling a strain-regulated phenomenon? – a finite element analysis. JBMR 15: 301-307.
  140. Smit TH, Schneider E and Odgaard A (1998): Star Length Distribution: a volume-based concept for the characterisation of structural anisotropy. J. Microscopy 191(3): 249-257.
  141. Smit TH, Odgaard A and Schneider E (1997): Structure and function of vertebral trabecular bone. Spine 22: 2823-2833.