Reference : Size does matter: an integrative in vivo-in silico approach for the treatment of crit...
Scientific journals : Article
Engineering, computing & technology : Multidisciplinary, general & others
http://hdl.handle.net/2268/183857
Size does matter: an integrative in vivo-in silico approach for the treatment of critical size bone defects.
English
Carlier, Aurelie [> >]
van Gastel, Nick [> >]
Geris, Liesbet mailto [Université de Liège > Département d'aérospatiale et mécanique > Génie biomécanique >]
Carmeliet, Geert [> >]
Van Oosterwyck, Hans [> >]
2014
PLoS computational biology
10
11
e1003888
Yes (verified by ORBi)
International
1553-734X
1553-7358
United States
[en] Although bone has a unique restorative capacity, i.e., it has the potential to heal scarlessly, the conditions for spontaneous bone healing are not always present, leading to a delayed union or a non-union. In this work, we use an integrative in vivo-in silico approach to investigate the occurrence of non-unions, as well as to design possible treatment strategies thereof. The gap size of the domain geometry of a previously published mathematical model was enlarged in order to study the complex interplay of blood vessel formation, oxygen supply, growth factors and cell proliferation on the final healing outcome in large bone defects. The multiscale oxygen model was not only able to capture the essential aspects of in vivo non-unions, it also assisted in understanding the underlying mechanisms of action, i.e., the delayed vascularization of the central callus region resulted in harsh hypoxic conditions, cell death and finally disrupted bone healing. Inspired by the importance of a timely vascularization, as well as by the limited biological potential of the fracture hematoma, the influence of the host environment on the bone healing process in critical size defects was explored further. Moreover, dependent on the host environment, several treatment strategies were designed and tested for effectiveness. A qualitative correspondence between the predicted outcomes of certain treatment strategies and experimental observations was obtained, clearly illustrating the model's potential. In conclusion, the results of this study demonstrate that due to the complex non-linear dynamics of blood vessel formation, oxygen supply, growth factor production and cell proliferation and the interactions thereof with the host environment, an integrative in silico-in vivo approach is a crucial tool to further unravel the occurrence and treatments of challenging critical sized bone defects.
http://hdl.handle.net/2268/183857
10.1371/journal.pcbi.1003888
FP7 ; 279100 - BRIDGE - Biomimetic process design for tissue regeneration: from bench to bedside via in silico modelling

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Open access
PLoS CB_2014_Carlier.pdfPublisher postprint3.2 MBView/Open

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.