Title
Occurrence And Treatment Of Bone Atrophic Non-Unions Investigated By An Integrative Approach
Abstract
Recently developed atrophic non-union models are a good representation of the clinical situation in which many non-unions develop. Based on previous experimental studies with these atrophic non-union models, it was hypothesized that in order to obtain successful fracture healing, blood vessels, growth factors, and (proliferative) precursor cells all need to be present in the callus at the same time. This study uses a combined in vivo-in silico approach to investigate these different aspects (vasculature, growth factors, cell proliferation). The mathematical model, initially developed for the study of normal fracture healing, is able to capture essential aspects of the in vivo atrophic non-union model despite a number of deviations that are mainly due to simplifications in the in silico model. The mathematical model is subsequently used to test possible treatment strategies for atrophic non-unions (i.e. cell transplant at post-osteotomy, week 3). Preliminary in vivo experiments corroborate the numerical predictions. Finally, the mathematical model is applied to explain experimental observations and identify potentially crucial steps in the treatments and can thereby be used to optimize experimental and clinical studies in this area. This study demonstrates the potential of the combined in silico-in vivo approach and its clinical implications for the early treatment of patients with problematic fractures.
Year
DOI
Venue
2010
10.1371/journal.pcbi.1000915
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
genetics,chondrogenesis,proliferating cell nuclear antigen,computer simulation,mathematical model,molecular biology,ecology,cell proliferation
Cell movement,Biology,In vivo,Bone healing,Bioinformatics,In silico
Journal
Volume
Issue
ISSN
6
9
1553-7358
Citations 
PageRank 
References 
2
0.58
1
Authors
5
Name
Order
Citations
PageRank
Liesbet Geris1114.82
Anita A C Reed220.58
Jos Vander Sloten33113.24
A Hamish R W Simpson420.58
Hans Van Oosterwyck5238.51