A5085100888- Cellular Mechanics and Interactions
- Bone Tissue Engineering Materials
- Collagen: Extraction and Characterization
- 3D Printing in Biomedical Research
- Electrospun Nanofibers in Biomedical Applications
- Nerve injury and regeneration
- Tissue Engineering and Regenerative Medicine
- Cell Adhesion Molecules Research
- Tendon Structure and Treatment
- Silk-based biomaterials and applications
- Wound Healing and Treatments
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Osteoarthritis Treatment and Mechanisms
- Anesthesia and Pain Management
- Nausea and vomiting management
- Biomedical Ethics and Regulation
- Angiogenesis and VEGF in Cancer
- Anesthesia and Sedative Agents
- Chemical Synthesis and Analysis
- Connective tissue disorders research
- Protease and Inhibitor Mechanisms
- Muscle Physiology and Disorders
- Breast Cancer Treatment Studies
- Laser Applications in Dentistry and Medicine
Eli Lilly (United States)
2022-2024
University of Wisconsin–Madison
2018-2024
Imperial College London
2006-2020
University College London
2008-2018
University of Manchester
1978-2018
Stanmore College
2007-2018
University of California, Davis
1985-2014
Royal National Orthopaedic Hospital
1992-2012
Draper Laboratory
2012
NIHR Oxford Musculoskeletal Biomedical Research Centre
2009
Abstract Currently, the concept of engineered tissues depends on ability cultured cells to fabricate new tissue around a scaffold. This is inherently slow and expensive has had limited success so far. We report here process for cell‐independent, controlled engineering biomimetic scaffolds by rapid removal fluid from hyperhydrated collagen gel (or other) constructs, using plastic compression (PC). PC fabrication produces dense, cellular, mechanically strong native structures with controllable...
One hundred ten local breast recurrences were observed in 1108 pathologically evaluable patients enrolled NSABP protocol 6 who treated by lumpectomy and followed for 5 to 95 months (average, 39 months). Eighty-six percent 95% of all noted within 4 years, respectively, following lumpectomy. Life table analysis revealed their incidence be 24% those not 6% receiving irradiation. four (95%) the involved mammary parenchyma remaining (5%) skin and/or nipple only. Eleven (10%) former noninvasive....
Human dermal fibroblasts (HDFs) in free-floating collagen matrices show minimal proliferation, although this may increase when the matrix is 'under tension'. We have investigated detailed mechanics underlying one of possible controls important cell behaviour, particular hypothesis that a response to substrate stiffness. Hyperhydrated gels were plastic-compressed (PC) give predetermined density and Mechanical properties tested using dynamic mechanical analyser; number by Alamar blue assay. In...
Tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor (GIPR/GLP-1R) agonist, has, in clinical trials, demonstrated greater reductions glucose, body weight, and triglyceride levels compared with selective GLP-1R agonists people type 2 diabetes (T2D). However, cellular mechanisms by which GIPR agonism may contribute to these improved efficacy outcomes have not been fully defined. Using human adipocyte mouse models, we investigated how long-acting regulate...
Many soft connective tissues are under endogenous tension, and their resident cells generate considerable contractile forces on the extracellular matrix. The present work was aimed to determine quantitatively how fibroblasts, grown within three-dimensional collagen lattices, respond mechanically precisely defined tensional loads. Forces generated in response changes applied load were measured using a culture force monitor. In number of variant systems, consistently reacted modify matrix...
The contraction of a collagen lattice by resident fibroblasts causes strains to be developed within that lattice. These can increased or decreased altering the aspect ratio (ratio length/width/thickness) fibroblast populated lattice, as cross-sectional area resisting strain is changed and application an external load. align themselves with direction maximum principle strain; in effect, these cells are "hiding" from perceived strain. pre-determined use computational finite element analysis....
Abstract While matrix stiffness has been implicated in cell adhesion and migration, most studies have focused on the effects of substrate 2D. The present work describes a novel continuous gradient model for studying such processes 3D. Wedge‐shaped collagen scaffolds were compressed to produce sheets desired (0.1 mm) uniform thickness, but with increasing density along length sheet. Dynamic mechanical analysis, carried out 1 mm wide strips obtained from two ends middle each sheet, showed that...
Collagen gel is a poroelastic/biphasic system consisting of fibrillar loose lattice structure filled with >99% fluid. Its mechanical behaviour governed by the inherent viscoelasticity fibrils, and their interaction This study investigated underlying mechanisms plastic compression (PC), recently introduced technique for production dense collagen matrices tissue engineering. Unconfined compressive loading results in rapid expulsion fluid phase to produce scaffolds improved properties...
Significance Mycobacteria, including the notorious pathogen Mycobacterium tuberculosis , possess a mycolic acid membrane that is barrier to antibiotics. Although key enzymes generate this structure are known, full understanding of cell envelope assembly lacking. We synthesized fluorogenic analog trehalose monomycolate, building block used by mycolyltransferase construct membrane. When analog, termed QTF, processed in cells mycolyltransferases, fluorescence generated. Thus, biosynthesis can...
SignificanceTirzepatide is a dual agonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 (GLP-1R), which are incretin receptors that regulate carbohydrate metabolism. This investigational agent has proven superior to selective GLP-1R agonists in clinical trials subjects with type 2 diabetes mellitus. Intriguingly, although tirzepatide closely resembles native GIP how it activates GIPR, differs markedly from GLP-1 its activation GLP-1R,...
Abstract A better understanding of the mechanisms nerve regeneration could improve outcome surgical repair. We have previously shown that axonal is increased by growth factor. Neurotrophin‐3 (NT‐3) belongs to same family as factor but acts on a distinct neuron subpopulation. As little known about its role following injury, we investigated effect NT‐3 delivered via fibronectin mats, support comparable grafts. stimulation (0.1–1000 ng/ml) neurite extension from embryonic chick dorsal root...
We report a novel implantable device that will deliver tethered aligned collagen guidance conduit containing Schwann cells into peripheral nerve injury site. Cells (Schwann and fibroblasts) incorporated rectangular gels contracted resulted in uniaxial alignment. This tissue-engineered construct was tested three-dimensional culture demonstrated the ability to guide neurite extension from dissociated dorsal root ganglia. A silicone tube adapted provide tethering sites for an such...
Fibroblast contraction in wound healing involves the interaction of several cell types, cytokines, and extracellular matrix molecules. We have previously developed fibroblast alignment models using precise uniaxial mechanical loads 3D culture contact guidance on fibronectin strands. Our aim here was to use place fibroblasts their potentially most sensitive configuration, i.e., perpendicular axis loading, present cells with conflicting cues. Gene expression at mRNA level recovered from...
Abstract It has been shown that the insulin‐like growth factor (IGF‐I) gene is spliced in response to mechanical signals producing forms of IGF‐I which have different actions. In order study how influence this splicing developing muscle, C 2 12 cells were grown three‐dimensional (3D) culture and subjected regimens strain. IGF‐IEa initiates fusion myoblasts form myotubes was found be constitutively expressed (held under endogenous tension) its expression upregulated by a single ramp stretch...
Plastic compression of hyperhydrated collagen gels produces tissue-like scaffolds enhanced biomechanical properties. By increasing density, these could be developed into highly Biomimetic cell-seeded templates. When utilizing three-dimensional (3-D) scaffold systems for tissue repair, and indeed when investigating the cytocompatibility two-dimensional (2-D) surfaces, cell seeding density is often overlooked. In this study, we investigated potentially critical parameter using MG-63 cells...
Abstract Cell‐level mechanical and 3D spatial cues are essential to the organization architecture of new tissues that form during growth, repair or in bioreactors. Fibroblast‐seeded collagen constructs have been used as bioartifical extracellular matrix (ECM) providing a environment embedded resident cells. As cells attach scaffold fibrils, they generate quantifiable contractile forces which depend on cell type, attachment, density, growth factors, stiffness. The aim this study was quantify...
A problem with tissue engineering scaffolds is maintaining seeded cell viability and function due to limitations of oxygen nutrient transfer. An approach maintain suitable concentrations throughout the scaffold would be controllably incorporate microchannelling within these scaffolds. This study investigated incorporation unidirectionally aligned soluble phosphate based glass fibers (PGF) into dense collagen PGF are degradable, their degradation can controlled through chemistry dimensions....
To investigate the absorption of aerosolized drugs from rat lung, anesthetized animals were allowed to inhale through a tracheal cannula liquid aerosols drug solutions generated with an air-jet nebulizer. The had mass median aerodynamic diameter 2.81 +/- 0.08 micron and geometric standard deviation 2.53 0.05. At various times after aerosol inhalation, lungs removed assayed for amount compound that not been absorbed. (min) necessary 50% were: antipyrine, 0.25; salicylic acid, 0.67; barbital,...