A5027413155- Tuberous Sclerosis Complex Research
- 3D Printing in Biomedical Research
- Renal and related cancers
- Extracellular vesicles in disease
- Nerve injury and regeneration
- Glycosylation and Glycoproteins Research
- Hydrogels: synthesis, properties, applications
- Neurogenesis and neuroplasticity mechanisms
- Mesenchymal stem cell research
- Tissue Engineering and Regenerative Medicine
- Monoclonal and Polyclonal Antibodies Research
- Freezing and Crystallization Processes
- Cellular Mechanics and Interactions
- Proteoglycans and glycosaminoglycans research
- Electrospun Nanofibers in Biomedical Applications
- Photochromic and Fluorescence Chemistry
- Physiological and biochemical adaptations
- Supramolecular Self-Assembly in Materials
- nanoparticles nucleation surface interactions
- Pluripotent Stem Cells Research
- Spinal Cord Injury Research
- Spaceflight effects on biology
- Protein purification and stability
- Epigenetics and DNA Methylation
- Muscle Physiology and Disorders
Health Canada
2020-2023
University of Toronto
2012-2019
Ottawa Hospital
2017-2018
Ottawa Hospital Research Institute
2017-2018
Occupational Cancer Research Centre
2014-2018
University of Ottawa
2008-2017
Toronto Public Health
2015-2016
Marie Curie
2011
Engineered hydrogels have been extensively used to direct cell function in 3D culture models, which are more representative of the native cellular microenvironment than conventional 2D culture. Previously, hyaluronan-furan and bis-maleimide polyethylene glycol were synthesized via Diels–Alder chemistry at acidic pH, did not allow encapsulation viable cells. In order enable gelation physiological reaction kinetics accelerated by replacing with electron-rich hyaluronan-methylfuran. These new...
ConspectusConventional cell culture techniques using 2D polystyrene or glass have provided great insight into key biochemical mechanisms responsible for cellular events such as proliferation, differentiation, and cell–cell interactions. However, the physical chemical properties of in vitro are dramatically different than those found native microenvironment vivo. Cells grown on substrates differ significantly from vivo, this explains, part, why many promising drug candidates discovered...
Design of experiment is used to develop a hybrid methylcellulose hydrogel that combines physical and chemical crosslinks, resulting in an injectable, situ stiffening, long-lasting material with predictable swelling rheological properties. Chemical crosslinking complete prior injection, allowing for ease use storage. Controlled release two relevant protein therapeutics biocompatibility the are demonstrated. As service our authors readers, this journal provides supporting information supplied...
Hydrogels are used to create 3D microenvironments with properties that direct cell function. The current study demonstrates the versatility of hyaluronic acid (HA)-based hydrogels independent control over hydrogel such as mechanics, architecture, and spatial distribution biological factors. were prepared by reacting furan-modified HA bis-maleimide-poly(ethylene glycol) in a Diels–Alder click reaction. Biomolecules photopatterned into two-photon laser processing, resulting spatially defined...
For native breast cancer cell growth to be mimicked in vitro as spheroids, a well-defined matrix that mimics the tumor microenvironment is required. Finding biomimetic material for 3D culture other than Matrigel has challenged field. Because hyaluronan naturally abundant and can chemically modified, we synthesized (HA) hydrogel with independently tunable mechanical chemical properties of cells. By modifying HA distinct bioorthogonal functional groups, its are controlled by cross-linking via...
Abstract Background Extracellular vesicles (EVs) produced by human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) are currently investigated for their clinical effectiveness towards immune-mediated diseases. The large amounts of stem cell-derived EVs required testing suggest that bioreactor production systems may be a more amenable alternative than conventional EV methods manufacturing products therapeutic use in humans. Methods To characterize the potential utility these systems,...
The role of hydration in modulating solution conformation, molecular recognition, and biological activity oligosaccharides, proteins, nucleotides is widely recognized but often neglected when investigating many processes such as the mechanism by which antifreezes inhibit growth ice. We have investigated relationship between carbohydrate configuration recrystallization-inhibition (RI) functional C-linked antifreeze glycoprotein (AFGP) analogues using a series 1−4. While 1−4 did not show any...
The ice recrystallization inhibition activity of various mono- and disaccharides has been correlated with their ability to cryopreserve human cell lines at concentrations. Cell viabilities after cryopreservation were compared control experiments where cells cryopreserved dimethylsulfoxide (DMSO). most potent inhibitors 220 mM solutions disaccharides; however, the best viability was obtained when a 200 d-galactose solution utilized. This minimally cytotoxic physiological temperature...
Several simple mono- and disaccharides have been assessed for their ability to inhibit ice recrystallization. Two carbohydrates were found be effective recrystallization inhibitors. D-galactose (1) was the best monosaccharide D-melibiose (5) most active disaccharide. The of each carbohydrate growth correlated its respective hydration number reported in literature. A reflects tightly bound water molecules is a function stereochemistry. It discovered that using absolute does not allow one...
With the goal of controlling stem cell fate, for ultimate application in delivery, we synthesized a delivery vehicle comprised an injectable hydrogel hyaluronan (HA) and methyl cellulose (MC) wherein MC is modified to allow bio-orthogonal coupling chemistry. Specifically, was using thiol-maleimide biotin–streptavidin chemistry covalently conjugate adhesive peptide, glycine–arginine–glycine–aspartic acid–serine (GRGDS), oligodendrocyte-differentiating factor, recombinant platelet-derived...
Many 3D in vitro models induce breast cancer spheroid formation; however, this alone does not recapitulate the complex vivo phenotype. To effectively screen therapeutics, it is urgently needed to validate against gold standard of xenografts. A new oxime-crosslinked hyaluronan (HA) hydrogel designed, manipulating gelation rate and mechanical properties grow spheroids 3D. This HA-oxime model maintains gene expression profile most similar that tumor xenografts based on a pan-cancer (comprising...
Cell behavior is highly dependent upon microenvironment. Thus, to identify drugs targeting metastatic cancer, screens need be performed in tissue mimetic substrates that allow cell invasion and matrix remodeling. A novel biomimetic 3D hydrogel platform enables quantitative analysis of viability at the individual level developed using automated data acquisition methods with an invasive lung disease (lymphangioleiomyomatosis, LAM) characterized by hyperactive mammalian target rapamycin complex...
Biomimetic scaffolds are desirable for 3D cell culture, yet optically transparent, macroporous, polysaccharide hydrogels have been limited. By incorporating soluble mono- and disaccharide additives during cryogelation, we synthesized biomimetic gained insight into the mechanism of their formation. The mono/disaccharide affect size ice crystal porogens interact with polymers, altering cryogel pore mechanical properties. Importantly, gel transparency is maintained following removal additives,...
Characterization of the structural diversity glycans by liquid chromatography–tandem mass spectrometry (LC–MS/MS) remains an analytical challenge in large-scale glycomics applications because presence heterogeneous composition, ubiquitous isomers, lability post-translational glycan modifications, and complexity data interpretation. High-resolution separation isomers differentiating from positional, linkage, branching, anomeric structures is often a prerequisite to ensure comprehensive...
Antifreeze glycoproteins (AFGPs) are a unique class of proteins that found in many organisms inhabiting subzero environments and ensure their survival by preventing ice growth vivo. During the last several years, our laboratory has synthesized functional C-linked AFGP analogues (3 5) possess custom-tailored antifreeze activity suitable for medical, commercial, industrial applications. These compounds potent inhibitors recrystallization do not exhibit thermal hystersis. The current study...