<i>In silico</i>design of treatment strategies in wound healing and bone fracture healing

Geris, Liesbet; Schugart, Richard C.; Oosterwyck, Hans Van

doi:10.1098/rsta.2010.0056

Cited by 26 publications

(21 citation statements)

References 144 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In all cases, the simulations were able to capture observed experimental and clinical outcomes. Moreover, in silico experiments were conducted to design potential treatment strategies for the various non-union models [15], [18], [19] however, these predictions were not corroborated by dedicated experiments as is the case in this study.…”

Section: Methodsmentioning

confidence: 66%

Occurrence and Treatment of Bone Atrophic Non-Unions Investigated by an Integrative Approach

et al. 2010

View full text Add to dashboard Cite

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.

show abstract

Section: Methodsmentioning

confidence: 66%

Occurrence and Treatment of Bone Atrophic Non-Unions Investigated by an Integrative Approach

et al. 2010

View full text Add to dashboard Cite

show abstract

“…When a different set of mechanics dependent parameters (still related to angiogenesis and osteogenesis) was used in the here proposed modeling framework (e.g., a subset of the parameters used in this study for case 3), nonunion formation was still predicted under overloading conditions. The influence of the exact set of the mechanics dependent parameters on the simulation results only became obvious when treatment strategies for these obtained overload-induced nonunions were implemented (Geris et al 2010b). …”

Section: Modeling Framework Assumptions Validation and Sensitivitymentioning

confidence: 98%

“…Furthermore, mathematical models can play a role in the development of treatment strategies and the design of animal experiments. Previous work by the authors has focused on the biological aspects of the regeneration process and the use of biological agents (growth factors and cells) to treat fracture nonunions (Geris et al 2008(Geris et al , 2010a). The bioregulatory model describes fracture healing based on the spatial and temporal evolution of cell and matrix densities and growth factor concentrations.…”

Section: Introductionmentioning

confidence: 99%

Connecting biology and mechanics in fracture healing: an integrated mathematical modeling framework for the study of nonunions

Geris

Sloten

Oosterwyck

2010

Biomech Model Mechanobiol

Self Cite

View full text Add to dashboard Cite

Both mechanical and biological factors play an important role in normal as well as impaired fracture healing. This study aims to provide a mathematical framework in which both regulatory mechanisms are included. Mechanics and biology are coupled by making certain parameters of a previously established bioregulatory model dependent on local mechanical stimuli. To illustrate the potential added value of such a framework, this coupled model was applied to investigate whether local mechanical stimuli influencing only the angiogenic process can explain normal healing as well as overload-induced nonunion development. Simulation results showed that mechanics acting directly on angiogenesis alone was not able to predict the formation of overload-induced nonunions. However, the direct action of mechanics on both angiogenesis and osteogenesis was able to predict overload-induced nonunion formation, confirming the hypotheses of several experimental studies investigating the interconnection between angiogenesis and osteogenesis. This study shows that mathematical models can assist in testing hypothesis on the nature of the interaction between biology and mechanics.

show abstract

“…On DNA level, we report [26,30] as references on tumor sensitivity with respect to DNA. A review on macroscopic modelling combined with ther-apies related to wound healing is given in [18]. Further examples are [26,31].…”

Section: Introductionmentioning

confidence: 99%

Particle methods to solve modelling problems in wound healing and tumor growth

Vermolen

2015

Comp. Part. Mech.

View full text Add to dashboard Cite

The paper deals with a compilation of several of our modelling studies on particle methods used for simulation of wound healing and tumor growth processes. The paper serves as an introduction of our modelling approaches to researchers with interest in biological cell-based models that use particle-based modelling approaches. The particles that we consider in the present models mimic either cells or points on cell boundaries that are allowed to migrate as a result of several chemical and mechanical factors. A distinct feature of our modelling frameworks with respect to conventional particle models, is that cells, mimicked by particles, are allowed to divide, differentiate and to die as a result of apoptosis or any causes for cell death. The paper is merely descriptive, rather than written in full mathematical rigor, and will show some of the potentials of the applied modelling.

show abstract

In silicodesign of treatment strategies in wound healing and bone fracture healing

Cited by 26 publications

References 144 publications

Occurrence and Treatment of Bone Atrophic Non-Unions Investigated by an Integrative Approach

Occurrence and Treatment of Bone Atrophic Non-Unions Investigated by an Integrative Approach

Connecting biology and mechanics in fracture healing: an integrated mathematical modeling framework for the study of nonunions

Particle methods to solve modelling problems in wound healing and tumor growth

Contact Info

Product

Resources

About