Sensitivity of tissue differentiation and bone healing predictions to tissue properties

Isaksson, Hanna; Donkelaar, Corrinus C. van; Ito, Keita

doi:10.1016/j.jbiomech.2009.01.001

Cited by 68 publications

(41 citation statements)

References 73 publications

(69 reference statements)

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“…Taken together, BMPs contribute to the differentiation of progenitor cells to nonosteoblast fates, such as adipose and cartilage in addition to or instead of bone, which can compromise the structural stability of newly formed bone. [90][91][92] Our laboratory has already proven the principle that Nell-1 delivered by adenovirus improves spinal fusion rate in rats. 85 The major advantages of using soluble Nell-1 protein are the avoidance of immunological complications related to adenoviral gene therapy, and an improved ability to control the therapeutic dose, both by adjusting the amount of Nell-1 protein delivery and designing biomaterials to control the rate and timing of delivery (discussed below).…”

Section: Nell-1 Mediates Bone Formation In Sheep Spinal Fusionmentioning

confidence: 99%

Nell-1 Protein Promotes Bone Formation in a Sheep Spinal Fusion Model

Siu

et al. 2011

Tissue Engineering Part A

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Bone morphogenetic proteins (BMPs) are widely used as bone graft substitutes in spinal fusion, but are associated with numerous adverse effects. The growth factor Nel-like molecule-1 (Nell-1) is mechanistically distinct from BMPs and can minimize complications associated with BMP therapies. This study evaluates the efficacy of Nell-1 combined with demineralized bone matrix (DBM) as a novel bone graft material for interbody spine fusion using sheep, a phylogenetically advanced animal with biomechanical similarities to human spine. Nell-1 + sheep DBM or Nell-1 + heat-inactivated DBM (inDBM) (to determine the osteogenic effect of residual growth factors in DBM) were implanted in surgical sites as follows: (1) DBM only (control) (n = 8); (2) DBM + 0.3 mg/mL Nell-1 (n = 8); (3) DBM + 0.6 mg/mL Nell-1 (n = 8); (4) inDBM only (control) (n = 4); (5) inDBM + 0.3 mg/mL Nell-1 (n = 4); (6) inDBM + 0.6 mg/mL Nell-1 (n = 4). Fusion was assessed by computed tomography, microcomputed tomography, and histology. One hundred percent fusion was achieved by 3 months in the DBM + 0.6 mg/mL Nell-1 group and by 4 months in the inDBM + 0.6 mg/mL Nell-1 group; bone volume and mineral density were increased by 58% and 47%, respectively. These fusion rates are comparable to published reports on BMP-2 or autograft bone efficacy in sheep. Nell-1 is an independently potent osteogenic molecule that is efficacious and easily applied when combined with DBM.

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Section: Nell-1 Mediates Bone Formation In Sheep Spinal Fusionmentioning

confidence: 99%

Nell-1 Protein Promotes Bone Formation in a Sheep Spinal Fusion Model

Siu

et al. 2011

Tissue Engineering Part A

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“…The choice of tissue material properties, one of the most important steps in FE model development [20,21], represents particularly high variability [22]. Parameters defining the underlying tissue differentiation hypothesis (e.g.…”

Section: Introductionmentioning

confidence: 99%

Prediction of fracture healing under axial loading, shear loading and bending is possible using distortional and dilatational strains as determining mechanical stimuli

Steiner

Claes

Ignatius

et al. 2013

J. R. Soc. Interface.

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Numerical models of secondary fracture healing are based on mechanoregulatory algorithms that use distortional strain alone or in combination with either dilatational strain or fluid velocity as determining stimuli for tissue differentiation and development. Comparison of these algorithms has previously suggested that healing processes under torsional rotational loading can only be properly simulated by considering fluid velocity and deviatoric strain as the regulatory stimuli. We hypothesize that sufficient calibration on uncertain input parameters will enhance our existing model, which uses distortional and dilatational strains as determining stimuli, to properly simulate fracture healing under various loading conditions including also torsional rotation. Therefore, we minimized the difference between numerically simulated and experimentally measured courses of interfragmentary movements of two axial compressive cases and two shear load cases (torsional and translational) by varying several input parameter values within their predefined bounds. The calibrated model was then qualitatively evaluated on the ability to predict physiological changes of spatial and temporal tissue distributions, based on respective in vivo data. Finally, we corroborated the model on five additional axial compressive and one asymmetrical bending load case. We conclude that our model, using distortional and dilatational strains as determining stimuli, is able to simulate fracture-healing processes not only under axial compression and torsional rotation but also under translational shear and asymmetrical bending loading conditions.

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“…Moreover, the material properties of the granulation tissue are ill-defined. Different values for Young's modulus, porosity and permeability have been proposed -depending on where and when the tissue was collected -and the commonly used value for Poisson's ratio (0.167) is based on a value measured in cartilage (Jurvelin et al 1997;Isaksson et al 2009). The nature of the interstitial fluid is also unclear, and its viscosity remains unknown.…”

Section: Materials Properties Boundary and Initial Conditionsmentioning

confidence: 99%

Micromotion-induced peri-prosthetic fluid flow around a cementless femoral stem

Camine

Terrier

Pioletti

2017

Computer Methods in Biomechanics and Biomedical Engineering

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Micromotion-induced interstitial fluid flow at the bone-implant interface has been proposed to play an important role in aseptic loosening of cementless implants. High fluid velocities are thought to promote aseptic loosening through activation of osteoclasts, shear stress induced control of mesenchymal stem cells differentiation, or transport of molecules. In this study, our objectives were to characterize and quantify micromotion-induced fluid flow around a cementless femoral stem using finite element modeling. With a 2D model of the bone-implant interface and full-factorial design, we first evaluated the relative influence of material properties, and bone-implant micromotion and gap on fluid velocity. Transverse sections around a femoral stem were built from computed tomography images, while boundary conditions were obtained from experimental measurements on the same femur. In a second step, a 3D model was built from the same data-set to estimate the shear stress experienced by cells hosted in the peri-implant tissues. The full-factorial design analysis showed that local micromotion had the most influence on peak fluid velocity at the interface. Remarkable variations in fluid velocity were observed in the macrostructures at the surface of the implant in the 2D transverse sections of the stem. The 3D model predicted peak fluid velocities extending up to 2.2 mm/s in the granulation tissue and to 3.9 mm/s in the trabecular bone. Peak shear stresses on the cells hosted in these tissues ranged from 0.1 to 12.5 Pa. These results offer insight into mechanical stimuli encountered at the bone-implant interface.

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Sensitivity of tissue differentiation and bone healing predictions to tissue properties

Cited by 68 publications

References 73 publications

Nell-1 Protein Promotes Bone Formation in a Sheep Spinal Fusion Model

Nell-1 Protein Promotes Bone Formation in a Sheep Spinal Fusion Model

Prediction of fracture healing under axial loading, shear loading and bending is possible using distortional and dilatational strains as determining mechanical stimuli

Micromotion-induced peri-prosthetic fluid flow around a cementless femoral stem

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