Brouwers, J.E.M.

Donkelaar, van, C.C.

Huiskes, H.W.J.

Sengers, B.G.

English

Pure OAI Repository

 A computational model of the human growth plateCitation for published version (APA):Brouwers, J. E. M., Donkelaar, van, C. C., Sengers, B. G., & Huiskes, H. W. J. (2004). A computational model ofthe human growth plate. Poster session presented at Mate Poster Award 2004 : 9th Annual Poster Contest.Document status and date:Published: 01/01/2004Document Version:Publisher’s PDF, also known as Version of Record (includes final page, issue and volume numbers)Please check the document version of this publication:• A submitted manuscript is the version of the article upon submission and before peer-review. There can beimportant differences between the submitted version and the official published version of record. Peopleinterested in the research are advised to contact the author for the final version of the publication, or visit theDOI to the publisher's website.• The final author version and the galley proof are versions of the publication after peer review.• The final published version features the final layout of the paper including the volume, issue and pagenumbers.Link to publicationGeneral rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright ownersand it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.            • Users may download and print one copy of any publication from the public portal for the purpose of private study or research.            • You may not further distribute the material or use it for any profit-making activity or commercial gain            • You may freely distribute the URL identifying the publication in the public portal.If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license above, pleasefollow below link for the End User Agreement:www.tue.nl/taverneTake down policyIf you believe that this document breaches copyright please contact us at:openaccess@tue.nlproviding details and we will investigate your claim.Download date: 04. Oct. 202312/mhjA Computational model of the growth plateJ.E.M. Brouwers, C.C. v. Donkelaar, B.G.Sengers, R. HuiskesBiomechanics and Tissue engineering, Bone and Orthopaedic BiomechanicsIntroductionEndochondral ossification is the differentiation process ofcartilaginous into osseous tissue. A large variety of locallyproduced signaling molecules play a role in controlling thisprocess. However, data from the literature suggest thatPTHrP, Ihh and VEGF are the most important growth factors(GFs). Our aim was to quantitatively evaluate whether thesethree growth factors together can control the initiation anddevelopment of the fetal growth plate. For this purpose, weemployed a new, temporo-spatial finite element model.Material and methodsOnce initial hypertrophiation has started in the center of theanlage, organized columns of proliferating (PZ), prehyper-trophic (pHZ) and hypertrophic zones (HZ) emerge. PTHrP, Ihhand VEGF are produced in the articular perichondrium (PC),pHZ and HZ, respectively (Fig 1). These GFs need to be trans-ported through the bone, as they have their effects on cellsin a distinct zone.PTHrP chondriumPeri−PZpHZHZBONEIhhVEGFFigure 1: Left: Regula-tory effects of GFs, de-picted with solid (stimu-latory) or dotted (inhi-bitory) lines. Arrows be-tween zones indicate celldifferentiation. Right:PZ, pHZ, HZ and bonein the growth plate.A 1-D FE model was developed representing the distal halfof a human femur. All interactions of GFs as depicted in Fig1 were incorporated. All cells with surrounding extracellularmatrix were represented by groups of elements.Synthesis (s), diffusion (t) and decay (d) of all GFs determinedthe change in local GF concentration (c) per element:dcdt= s − t − d = s −∇.(D∇c) − ln2τc (1)in which half-life time (t) was assumed to be 10 minutes forall GFs [4]. The diffusion coefficient (D) was 63 mm2/s for thePZ, based on FRAP measurements in porcine growth plate.The proliferation rate in PZ was semi-dependent on Ihh. Allother processes, i.e. cell differentiation rate and ossification,were controlled by local GF concentration. All effects of GFswere concentration dependent following a Michaelis-Mentenequation. Lengths of cells and zones were taken from humandata [1, 2].ResultsA stable growth plate was formed, correctly simulating thehuman femoral growth plate. The number of cells varied cycli-cally within a small, physiological range (Fig 2). Bone growthwas found to be constant and self-regulating during the sim-ulation.0 5 10 150102030405060simulation time (days)number of cells per zonePZpHZHZ1.4 1.6 1.8 200.20.40.60.811.21.41.6position [mm]concentration [µg/mL]PTHrP Ihh VEGF PZ pHZ HZ BONE Figure 2: Left: Nr of cells per zone during the simulation. Right:PTHrP and Ihh profiles as a result of the transition of a cell from pHZto HZ. The subsequent PTHrP and Ihh decreases lead to a transitionof a cell from PZ to pHZ.DiscussionThe growth factors PTHrP, Ihh and VEGF together were ableto control the initiation and development of the growth platein a computational model, correctly simulating the develop-ment of the cartilage anlage to a mineralized bone at threemonths after birth.Enhanced or decreased GF synthesis resulted in new steadystates, which corresponded with changes seen in transgenicmice and with human growth plate pathologies (data notshown).The approach to model endochondral ossification in a longbone based on growth factor effects, is new and is a promis-ing addition to earlier computational models, which generallyfocussed on the mechanical environment in the tissue as atrigger for endochondral ossification.Future developments enable extensions to later developmen-tal stages, 2-D and 3-D representations, and incorporation ofthe interactions of mechanical loading and synthesis, trans-port and receptors of growth factors.References:[1] Fazzalari, et al., 1997, The anat. record 248:1-12[2] Kember, et al., 1976, JBJS 58-B: 426-35[3] Hunziker, et al., 1987, JBJS 69:162-72[4] Bailon-Plaza, et al., 2001, J. Theor. Biol. 212:191-209[5] Stevens, et al., 1999, JBJS 17:646-53

A computational model of the human growth plate

NARCIS 

Brouwers, JEM Julienne

Donkelaar, CC René  van

Sengers, BG Bram

Huiskes, HWJ Rik

Repository TU/e

https://pure.tue.nl/ws/files/3652473/916408685913464.pdf

A computational model of the human growth plate

Abstract

Similar works

Full text

Available Versions

Pure OAI Repository

NARCIS

Repository TU/e