Publications of Varun Manhas
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See detailIn silico modeling of bone formation under the influence of calcium phosphate-based biomaterials and osteochondrogenic growth factors
Manhas, Varun ULiege

Doctoral thesis (2017)

Bone regeneration is a complex process that involves regulation of different cell types by multiple biochemical, physical and mechanical factors. Unlike other biological tissues, bone can heal scarlessly ... [more ▼]

Bone regeneration is a complex process that involves regulation of different cell types by multiple biochemical, physical and mechanical factors. Unlike other biological tissues, bone can heal scarlessly and recover its original shape, size and strength. However, about 5% of bone defects result in non-unions. To tackle these non-unions, tissue engineering (TE) aims to develop bone substitutes or intelligent TE constructs to replace damaged, diseased or aging tissue. These bone substitutes/TE constructs are designed to support the chemotaxis, proliferation and differentiation of bone progenitor cells as well as being a biochemical agent delivery system. However, these delivery systems have a few limitations such as structural weakness of the carrier, high doses of biochemical agents being delivered due to burst release, unknown optimal concentrations of implanted cells and their high cost. Another drawback of these systems is the limited understanding on the relationship between biochemical agent dose, implanted cells, carrier volume, carrier material type and resultant bone formation. Given their significant medical potential, there is an increasing demand to design and develop improved bone substitutes/TE constructs. This PhD work fits in the long-term vision that mathematical models can be used as a part of design and manufacturing processes to develop improved treatment strategies and ultimately save experimental time and costs. In the first part of this work, a novel computational model was developed to predict the in vitro release of Ca2+ ions from calcium phosphate (CaP)-based scaffolds. The developed model was based on the Noyes-Whitney equation, the Fick’s second law of diffusion equation and the level-set method (LSM). The model was dependent on biophysicochemical phenomena such as dissolution, diffusion and degradation along with specific scaffold characteristics such as composition, size and shape. The predictions of the model were compared to dedicated experimental results. In the second part of this work, we investigated the use of a previously reported oxygen-dependent fracture healing model to elucidate the in vivo bone formation capacity of bone morphogenetic protein-2 (BMP-2) delivery systems in an ectopic environment. Specific attention was paid to the influence of BMP-2 dose and carrier volume on ectopic bone formation. The performance of this mathematical model was corroborated by comparison with experimental results published in the literature. Finally, the model was applied to investigate the influence of different BMP-2 release profiles on ectopic bone formation. In the third part of this work, we developed a novel computational model to predict the CaP and BMP-dependent ectopic bone formation in nude mice with and without incorporation of donor cells. The model specifically investigated the influence of BMP-2 dose, donor cell concentrations and calcium ion release on ectopic bone formation. The performance of this mathematical model was compared to the results of dedicated in-house experiments. The model was able to capture essential elements of the experimental results yet at the same time, a number of points for further improvement were identified. In the final part of this work, we investigated the application of the aforementioned CaP and BMP-dependent bone formation model to an orthotopic setting in sheep. The performance of the mathematical model was corroborated by comparing the model predictions with experimental results published in the literature. Subsequently, the model was applied to investigate the influence of different CaP-BMP-cell combinations on orthotopic bone formation, simulating in-house ongoing experiments. In conclusion, this PhD work illustrates a computational step taken towards enhancing the understanding on the role of CaP and BMPs in healing large bone defects. [less ▲]

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See detailModelling BMP-2 carrier device for bone tissue engineering application
Manhas, Varun ULiege; Carlier, Aurelie; Geris, Liesbet ULiege

Poster (2017, February 01)

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See detailAN IN-SILICO MODEL OF BMP-2 CARRIER DEVICE FOR BONE TISSUE ENGINEERING APPLICATION
Manhas, Varun ULiege; Carlier, Aurelie; Geris, Liesbet ULiege

Poster (2016, November 25)

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See detailMathematical modelling of ectopic bone formation in bone morphogenetic (BMP) carrier device
Manhas, Varun ULiege; Carlier, Aurelie; Geris, Liesbet ULiege

Conference (2016, September 28)

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See detailComputational modelling of local calcium ions release from calcium phosphate-based scaffolds
Manhas, Varun ULiege; Guyot, Yann; Kerckhofs, Greet et al

in Biomechanics & Modeling in Mechanobiology (2016)

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See detailMathematical modelling of the degradation behaviour of biodegradable metals
Bajger, P; Ashbourn, JMA; Manhas, Varun ULiege et al

in Biomechanics & Modeling in Mechanobiology (2016)

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See detailInvestigating in vitro calcium dissolution using a mathematical model
Manhas, Varun ULiege; Guyot, Yann; Kerckhofs, Greet et al

Scientific conference (2016, March)

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See detailModelling afferent nerve responses to bladder filling
Argungu, Maryam; Bayram, Saziye; Brook, Bindi et al

Report (2015)

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See detailModelling the regulation of immunoglobulin class switching to IgE and IgG in human B cells to reduce animal use
Eljazi, R; Fear, D; Gould, H et al

Report (2015)

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See detailInvestigating cell-carrier combinations for bone formation using a mathematical model
Manhas, Varun ULiege; Guyot, Yann ULiege; Chai, Yoke C et al

Poster (2014, November 28)

This study describes the development and implementation of a bio-regulatory model that focuses on the Ca2+ release from CaP scaffolds and aims to determine the local Ca2+ concentration of different ... [more ▼]

This study describes the development and implementation of a bio-regulatory model that focuses on the Ca2+ release from CaP scaffolds and aims to determine the local Ca2+ concentration of different clinical grade CaP scaffold types during bone formation. [less ▲]

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See detailInvestigating local Ca2+ concentration in calcium phosphate scaffolds for bone tissue engineering applications
Manhas, Varun ULiege; Guyot, Yann ULiege; Chai, Yoke C et al

Conference (2014, October)

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See detailMathematical modelling of bone formation based on local Ca2+ concentrations in calcium phosphate scaffolds
Manhas, Varun ULiege; Guyot, Yann; Chai, Yoke Chin et al

Poster (2014, September)

In tissue engineering applications, scaffolds act as carriers for cells and growth factors that restore the functionality of an organ either permanently or temporarily. Since their introduction, calcium ... [more ▼]

In tissue engineering applications, scaffolds act as carriers for cells and growth factors that restore the functionality of an organ either permanently or temporarily. Since their introduction, calcium phosphates (CaP) have proven to be an excellent bone substitute material, however, the complexity of the in vitro and in vivo behavior has not been elucidated completely. Computational models can help us to gain a comprehensive understanding of this complexity, allowing improvement of the design for optimal bone healing. For the development of a mathematical model accounting for the complexity of CaP driven bone formation, this study focuses on the Ca2+ release from CaP scaffolds and aims to determine the local Ca2+ concentration of different clinical grade CaP scaffold types during bone formation. [less ▲]

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See detailSerum Vascular Endothelial Growth Factor is Selectively Upregulated in Patients with Biopsy-Proven Giant Cell Arteritis
Morlet, Julien; Mahoney, David; Zarei, Ali et al

in Rheumatology (2014), 53(1), 188-188

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See detailAssessing local Ca2+ concentrations in calcium phosphate scaffolds by computational modelling
Manhas, Varun ULiege; Guyot, Yann ULiege; Chai, Yoke Chin et al

Poster (2013, October 24)

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See detailComputational modelling of aneurysm risk in giant cell arteritis (GCA)
Manhas, Varun ULiege; Piper, Jennifer; Singh, Surjeet et al

Scientific conference (2013, September)

Detailed reference viewed: 27 (5 ULiège)
See detailPreparation and characterization of sonosensitive nanoparticles for cavitation-aided therapeutics
Manhas, Varun ULiege; Schiffter, Heiko A; Arora, Manish

Scientific conference (2012, May)

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See detailStandardisation of the use of Ultrasound as a diagnostic tool in the diagnosis of Giant Cell Arteritis (GCA)
Piper, Jennnifer; Singh, Surjeet; Masters, Shauna et al

Scientific conference (2012, May)

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See detailBiocompatible solid particles for controlled instigation of cavitation during therapeutic ultrasound.
Arora, Manish; Schiffter, Heiko; Manhas, Varun ULiege et al

in Journal of the Acoustical Society of America (2010, October), 128(4), 2440

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See detailBiodegradable micro- and nanoparticles for controlled cavitation inception in water and porcine blood
Schiffter, Heiko; Manhas, Varun ULiege; Arora, Manish

Scientific conference (2010, May 25)

Detailed reference viewed: 15 (2 ULiège)