Angiogenesis in bone fracture healing: A bioregulatory model

Geris, Liesbet; Gerisch, Alf; Sloten, Jos Vander; Weiner, Rüdiger; Oosterwyck, Hans Van

doi:10.1016/j.jtbi.2007.11.008

Cited by 214 publications

(239 citation statements)

References 101 publications

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“…Normal Fracture Healing Initially, it was assumed that vessels could only grow into the callus from the periosteum of the cortical bone (Burke and Kelly, 2012;Burke et al, 2013;Geris et al, 2008;Chen et al, 2009;Carlier et al, 2015). 3 % of the lattice points on this edge contained active vessels.…”

Section: Simulationsmentioning

confidence: 99%

A computational model to explore the role of angiogenic impairment on endochondral ossification during fracture healing

O'Reilly

Hankenson

Kelly

2016

Biomech Model Mechanobiol

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While it is well established that an adequate blood supply is critical to successful bone regeneration, it remains poorly understood how progenitor cell fate is affected by the altered conditions present in fractures with disrupted vasculature. In this study, computational models were used to explore how angiogenic impairment impacts oxygen availability within a fracture callus and hence regulates mesenchymal stem cell (MSC) differentiation and bone regeneration. Tissue differentiation was predicted using a previously developed algorithm which assumed that MSC fate is governed by the local oxygen tension and substrate stiffness. This was updated to include conditions for oxygen regu- lated cell death and endochondral ossification. The updated algorithm was validated by using it within a model of normal fracture healing where it predicted the experimentally observed quantity and spatial distribution of bone and cartilage at 10 and 20 days post fracture (dpf). Furthermore, it also predicted the ratio of cartilage which had become hypertrophic at 10 dpf. Following this, three models of fracture healing with increasing levels of angiogenic impairment were developed. Under mild impairment the model predicted the experimentally observed reduction in hypertrophic cartilage at 10 dpf as well as the persistence of cartilage at 20 dpf. Models of more severe angiogenic impairment predicted the development of fibrous and necrotic tissue within the callus. These results provide insight into how environmental factors specific to an ischemic callus regulate tissue regeneration and provide support for the hypothesis that endochondral ossification during fracture healing is governed by the local oxygen tension.

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Section: Simulationsmentioning

confidence: 99%

A computational model to explore the role of angiogenic impairment on endochondral ossification during fracture healing

O'Reilly

Hankenson

Kelly

2016

Biomech Model Mechanobiol

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“…Geris et al (2008a) started from the model of Bailón-Plaza & van der Meulen (2001) and introduced key aspects of healing such as angiogenesis and directed cell migration. A schematic overview of this model is presented in figure 3.…”

Section: Bone Regeneration (A ) Biology Of Bone Regenerationmentioning

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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“…Other mathematical models that incorporate these effects present a more irregular distribution of bone (Gómez-Benito et al, 2005;Geris et al, 2004Geris et al, , 2008.…”

mentioning

confidence: 99%

“…In parallel to inflammation, angiogenesis takes place and it is necessary as the only means of providing nutrients supply to the peri-implant healing compartment. In Geris et al (2008), the role of angiogenesis in bone fracture healing was considered.…”

mentioning

confidence: 99%