Daniel Vonwil

University of Freiburg

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V. Prasad Shastri

University of Freiburg

Iván Martín

University Hospital of Basel

Jon Christensen

University of California, Los Angeles

Andrea Barbero

University of Basel

M. Heberer

University Hospital of Basel

David Wendt

University Hospital of Basel

Lucas Ahrens

University of Freiburg

Daniel Gygax

FHNW University of Applied Sciences and Arts

E. Bonacina

Istituti di Ricovero e Cura a Carattere Scientifico

Simon Ströbel

Inspire

Cooperative Institutions

University of Freiburg

University of Basel

University Hospital of Basel

École Polytechnique Fédérale de Lausanne

ETH Zurich

Massachusetts Institute of Technology

University of Lausanne

University of Belgrade

Heidelberg University

John Wiley & Sons (United States)

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Assessment of the stability of TGFβ3 bioactivity for potential bioreactor applications

Biochemical Engineering Journal (2007)

Daniel Vonwil David Wendt Simon Ströbel Hans‐Joachim Wallny Daniel Gygax

10.1016/j.bej.2007.11.009

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Citations (7)

Validation of Fluorescence Molecular Tomography/Micro-CT Multimodal Imaging In Vivo in Rats

Molecular Imaging and Biology (2013)

Daniel Vonwil Jon Christensen Sascha B. Fischer Olaf Ronneberger V. Prasad Shastri

Biodistribution

X-ray microtomography

Molecular Imaging

Fluorescence-lifetime imaging microscopy

Whole body imaging

10.1007/s11307-013-0698-8

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Citations (24)

Engineered cartilage generated by nasal chondrocytes is responsive to physical forces resembling joint loading

Arthritis & Rheumatism (2007)

Christian Candrian Daniel Vonwil Andrea Barbero E. Bonacina Sylvie Miot

Abstract Objective To determine whether engineered cartilage generated by nasal chondrocytes (ECN) is responsive to different regimens of loading associated with joint kinematics and previously shown to be stimulatory of engineered cartilage generated by articular chondrocytes (ECA). Methods Human nasal and articular chondrocytes, harvested from 5 individuals, were expanded and cultured for 2 weeks into porous polymeric scaffolds. The resulting ECN and ECA were then maintained under static conditions or exposed to the following loading regimens: regimen 1, single application of cyclic deformation for 30 minutes; regimen 2, intermittent application of cyclic deformation for a total of 10 days, followed by static culture for 2 weeks; regimen 3, application of surface motion for a total of 10 days. Results Prior to loading, ECN constructs contained significantly higher amounts of glycosaminoglycan (GAG) and type II collagen compared with ECA constructs. ECN responded to regimen 1 by increasing collagen and proteoglycan synthesis, to regimen 2 by increasing the accumulation of GAG and type II collagen as well as the dynamic modulus, and to regimen 3 by increasing the expression of superficial zone protein, at the messenger RNA level and the protein level, as well as the release of hyaluronan. ECA constructs were overall less responsive to all loading regimens, likely due to the lower extracellular matrix content. Conclusion Human ECN is responsive to physical forces resembling joint loading and can up‐regulate molecules typically involved in joint lubrication. These findings should prompt future in vivo studies exploring the possibility of using nasal chondrocytes as a cell source for articular cartilage repair.

Regimen

10.1002/art.23155

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Citations (101)

Biotin-Avidin-Mediated Capture of Microspheres on Polymer Fibers

Molecules (2019)

Lucas Ahrens Daniel Vonwil Neha Arya Aurélien Forget V. Prasad Shastri

Systems for efficient and selective capture of micro-scale objects and structures have application in many areas and are of particular relevance for selective isolation of mammalian cells. Systems for the latter should also not interfere with the biology of the cells. This study demonstrates the capture of microspheres through orthogonal coupling using biotin (ligand) and (strept)avidin (receptor). Fibrous poly(ethylene terephthalate) (PET) meshes were hydrolyzed under controlled alkaline conditions to obtain activated surfaces with COOH groups allowing for the functionalization of the PET with biotin of various spacer length. The system capture efficiency was optimized by varying the length of spacer presenting the biotin against streptavidin. In a proof of concept experiment, avidin-functionalized microspheres were used as surrogates for cells, and their capture under dynamic conditions including virous mixing and high-flow rate perfusion is demonstrated. Functionalization of PET meshes with biotin conjugated to longest spacer yielded the most efficient capture of microspheres. These preliminary results lay the foundation for the development of biosystems for capture of specific cells under physiologically relevant conditions, using biorthogonal avidin-biotin interactions.

Avidin

Streptavidin

Surface Modification

10.3390/molecules24112036

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Citations (2)

Glycosylation facilitates transdermal transport of macromolecules

Proceedings of the National Academy of Sciences (2012)

Christopher J. Pino Jordan U. Gutterman Daniel Vonwil Samir Mitragotri V. Prasad Shastri

Stratum corneum, the outermost layer of skin, allows transport of only low-molecular weight (<500) lipophilic solutes. Here, we report a surprising finding that avicins ( Av s), a family of naturally occurring glycosylated triterpenes with a molecular weight > 2,000, exhibit skin permeabilities comparable to those of small hydrophobic molecules, such as estradiol. Systematic fragmentation of the Av molecule shows that deletion of the outer monoterpene results in a 62% reduction in permeability, suggesting an important role for this motif in skin permeation. Further removal of the tetrasaccharide residue results in a further reduction of permeability by 79%. These results, taken in sum, imply that synergistic effects involving both hydrophobic and hydrophilic residues may hold the key in facilitating translocation of Av s across skin lipids. In addition to exhibiting high permeability, Av s provided moderate enhancements of skin permeability of estradiol and polysaccharides, including dextran and inulin but not polyethylene glycol.

10.1073/pnas.1200942109

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Citations (15)

Generation of 3D Soluble Signal Gradients in Cell‐Laden Hydrogels Using Passive Diffusion

Advanced Biosystems (2018)

Lucas Ahrens Simon Tanaka Daniel Vonwil Jon Christensen Dagmar Iber

Soluble signal gradients play an important role in organ patterning, cell migration, and differentiation. Currently, signal gradients in 2D cell culture are realized using microfluidics and here cells are exposed to high and nonphysiological shear stress. Tissue morphogenesis (organogenesis) however occurs in 3D and therefore there is a need for simple and practical systems to impose gradients to cells dispersed in 3D matrix. Herein, a 3D gradient generator based on passive diffusion elements that recapitulates interstitial flow and is capable of imposing predictable gradients over long length scales (6 mm) lasting up to 48 h to cells dispersed in a hydrogel environment is reported. Using recombinant human WNT3A (rhWNT3A), the spatiotemporal activation of the canonical WNT pathway in human epithelial kidney cells and human mesenchymal stems cells expressing a green fluorescence protein reporter on a transcription factor/lymphoid enhancer-binding factor (TCF/LEF) promoter is demonstrated. By refining computation models based on experimental findings, the diffusion coefficient of rhWNT3A in presence of human cells in 3D is determined. Furthermore, the formation of rhBMP4 gradients is visualized using immunohistochemistry by staining for phospho-SMAD1/5, the downstream targets of the bone morphogenetic protein (BMP) pathway. The simplicity of the gradient generator is expected to spur its adoption in studying developmental biology paradigms in vitro.

SIGNAL (programming language)

10.1002/adbi.201800237

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Citations (9)

A Novel Method of Dynamic Culture Surface Expansion Improves Mesenchymal Stem Cell Proliferation and Phenotype

Stem Cells (2008)

Hicham Majd Pierre‐Jean Wipff Lara Buscemi Manuel Bueno Daniel Vonwil

Abstract Repeated passaging in conventional cell culture reduces pluripotency and proliferation capacity of human mesenchymal stem cells (MSC). We introduce an innovative cell culture method whereby the culture surface is dynamically enlarged during cell proliferation. This approach maintains constantly high cell density while preventing contact inhibition of growth. A highly elastic culture surface was enlarged in steps of 5% over the course of a 20-day culture period to 800% of the initial surface area. Nine weeks of dynamic expansion culture produced 10-fold more MSC compared with conventional culture, with one-third the number of trypsin passages. After 9 weeks, MSC continued to proliferate under dynamic expansion but ceased to grow in conventional culture. Dynamic expansion culture fully retained the multipotent character of MSC, which could be induced to differentiate into adipogenic, chondrogenic, osteogenic, and myogenic lineages. Development of an undesired fibrogenic myofibroblast phenotype was suppressed. Hence, our novel method can rapidly provide the high number of autologous, multipotent, and nonfibrogenic MSC needed for successful regenerative medicine.

Multipotent Stem Cell

Chondrogenesis

Regenerative Medicine

10.1634/stemcells.2008-0674

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Citations (69)

Direct quantification of dual protein adsorption dynamics in three dimensional systems in presence of cells

Acta Biomaterialia (2017)

Melika Sarem Daniel Vonwil Steffen Lüdeke V. Prasad Shastri

Dynamics

Protein Adsorption

10.1016/j.actbio.2017.05.021

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Citations (3)

Assessment of TGF-b3 bioactivity for potential bioreactor applications

Daniel Vonwil David Wendt Sami Stroebel Hans‐Joachim Wallny Daniel Gygax

Source

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Citations (1)

A novel bioreactor with mechanical stimulation for skeletal tissue engineering

Chemical Industry and Chemical Engineering Quarterly (2009)

Miloš Petrović D. V. Mitraković Branko Bugarski Daniel Vonwil Iván Martín

The provision of mechanical stimulation is believed to be necessary for the functional assembly of skeletal tissues, which are normally exposed to a variety of biomechanical signals in vivo. In this paper, we present a development and validation of a novel bioreactor aimed for skeletal tissue engineering that provides dynamic compression and perfusion of cultivated tissues. Dynamic compression can be applied at frequencies up to 67.5 Hz and displacements down to 5 ?m thus suitable for the simulation of physiological conditions in a native cartilage tissue (0.1-1 Hz, 5-10 % strain). The bioreactor also includes a load sensor that was calibrated so to measure average loads imposed on tissue samples. Regimes of the mechanical stimulation and acquisition of load sensor outputs are directed by an automatic control system using applications developed within the LabView platform. In addition, perfusion of tissue samples at physiological velocities (10-100 ?m/s) provides efficient mass transfer, as well as the possibilities to expose the cells to hydrodynamic shear and simulate the conditions in a native bone tissue. Thus, the novel bioreactor is suited for studies of the effects of different biomechanical signals on in vitro regeneration of skeletal tissues, as well as for the studies of newly formulated biomaterials and cell biomaterial interactions under in vivo-like settings.

Biomaterial

10.2298/ciceq0901041p

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Citations (22)