Simulation of fracture healing incorporating mechanoregulation of tissue differentiation and dispersal/proliferation of cells

Andreykiv, A.; Keulen, Fred van; Prendergast, Patrick J.

doi:10.1007/s10237-007-0108-8

Cited by 81 publications

(45 citation statements)

References 47 publications

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“…This implies that bone remodeling was significant only at late healing stages. Present mathematical models of bone healing (45)(46)(47) usually are based on the experimental observation that the main source of the stem cells is the periosteum, (48)(49)(50) and thus new bone tissue within the external mineralized callus is predicted to form first on the periosteal side and then into the osteotomy/fracture gap. Our study does support this concept in a way that callus mineral particles appeared to develop much earlier/faster in the periosteal region near the cortical bone ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Size and habit of mineral particles in bone and mineralized callus during bone healing in sheep

Liu

Manjubala

Schell

et al. 2010

Journal of Bone and Mineral Research

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Bone healing is known to occur through the successive formation and resorption of various tissues with different structural and mechanical properties. To get a better insight into this sequence of events, we used environmental scanning electron microscopy (ESEM) together with scanning small-angle X-ray scattering (sSAXS) to reveal the size and orientation of bone mineral particles within the regenerating callus tissues at different healing stages (2, 3, 6, and 9 weeks). Sections of 200 mm were cut from embedded blocks of midshaft tibial samples in a sheep osteotomy model with an external fixator. Regions of interest on the medial side of the proximal fragment were chosen to be the periosteal callus, middle callus, intercortical callus, and cortex. Mean thickness (T parameter), degree of alignment (r parameter), and predominant orientation (c parameter) of mineral particles were deduced from resulting sSAXS patterns with a spatial resolution of 200 mm. 2D maps of T and r overlapping with ESEM images revealed that the callus formation occurred in two waves of bone formation, whereby a highly disordered mineralized tissue was deposited first, followed by a bony tissue with more lamellar appearance in the ESEM and where the mineral particles were more aligned, as revealed by sSAXS. As a consequence, degree of alignment and mineral particle size within the callus increased with healing time, whereas at any given moment there were structural gradients, for example, from periosteal toward the middle callus. ß

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Section: Discussionmentioning

confidence: 99%

Size and habit of mineral particles in bone and mineralized callus during bone healing in sheep

Liu

Manjubala

Schell

et al. 2010

Journal of Bone and Mineral Research

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“…They used their model to investigate the influence of gap size and interfragmentary movement on the callus size. Andreykiv et al (2007) started from the mechanoregulatory model proposed by Prendergast et al (1997) and included diffusion, proliferation and differentiation of cell populations (mesenchymal stem cells, fibroblasts, chondrocytes and osteoblasts). Model parameters were selected based on the comparison with an in vivo experiment.…”

Section: (C ) and Back Againmentioning

confidence: 99%

In silicobiology of bone modelling and remodelling: regeneration

Geris

Sloten

Oosterwyck

2009

Phil. Trans. R. Soc. A.

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Bone regeneration is the process whereby bone is able to (scarlessly) repair itself from trauma, such as fractures or implant placement. Despite extensive experimental research, many of the mechanisms involved still remain to be elucidated. Over the last decade, many mathematical models have been established to investigate the regeneration process in silico. The first models considered only the influence of the mechanical environment as a regulator of the healing process. These models were followed by the development of bioregulatory models where mechanics was neglected and regeneration was regulated only by biological stimuli such as growth factors. The most recent mathematical models couple the influences of both biological and mechanical stimuli. Examples are given to illustrate the added value of mathematical regeneration research, specifically in the in silico design of treatment strategies for non-unions. Drawbacks of the current continuum-type models, together with possible solutions in extending the models towards other time and length scales are discussed. Finally, the demands for dedicated and more quantitative experimental research are presented.

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“…Furthermore, it assumes that all MSCs will respond identically to their mechanical environment, whereas in reality the bone marrow cell population in itself is highly heterogeneous. Cellular events and characteristics can be captured more accurately with extended continuum models (Andreykiv et al, 2008;Isaksson et al, 2008b,a) or lattice based approaches including stochastic components (Perez and Prendergast, 2007;Byrne et al, 2007;Checa and Prendergast, 2009a). Callus growth was not considered, but has been incorparated into other models (Gómez-Benito et al, 2005García-Aznar et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…where c cell is the current cell concentration and D = 0.34 mm 2 d −1 the diffusion coefficient (Lacroix et al, 2002;Andreykiv et al, 2008). Fluid flow and shear strain were used as mechanoregulatory stimuli for tissue differentiation Lacroix and Prendergast, 2002b,a;Isaksson et al, 2006a,b).…”

Section: Mechano-regulation Modelmentioning

confidence: 99%

Mechano-regulation of mesenchymal stem cell differentiation and collagen organisation during skeletal tissue repair

Nagel

Kelly

2009

Biomech Model Mechanobiol

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A number of mechano-regulation theories have been proposed that relate the differentiation pathway of mesenchymal stem cells (MSCs) to their local biomechanical environment. During spontaneous repair processes in skeletal tissues, the organisation of the extracellular matrix is a key determinant of its mechanical fitness. In this paper we extend the mechano-regulation theory proposed by Prendergast et al (1997) to include the role of the mechanical environment on the collagen architecture in regenerating soft tissues. A large strain anisotropic poroelastic material model is used in a simulation of tissue differentiation in a fracture subject to cyclic bending (Cullinane et al, 2002). The model predicts non-union with cartilage and fibrous tissue formation in the defect. Predicted collagen fibre angles, as determined by the principal decomposition of strainand stress-type tensors, are similar to the architecture seen in native articular cartilage and neoarthroses induced by bending of mid-femoral defects in rats. Both stress and strain based remodelling stimuli successfully predicted the general patterns of collagen fibre organisation observed in vivo. This provides further evidence that collagen organisation during tissue differentiation is determined by the mechanical environment. It is envisioned that such predictive models can play a key role in optimising MSC based skeletal repair therapies where recapitulation of the normal tissue architecture

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Simulation of fracture healing incorporating mechanoregulation of tissue differentiation and dispersal/proliferation of cells

Cited by 81 publications

References 47 publications

Size and habit of mineral particles in bone and mineralized callus during bone healing in sheep

Size and habit of mineral particles in bone and mineralized callus during bone healing in sheep

In silicobiology of bone modelling and remodelling: regeneration

Mechano-regulation of mesenchymal stem cell differentiation and collagen organisation during skeletal tissue repair

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