139 research outputs found
sj-docx-1-tej-10.1177_20417314221140500 – Supplemental material for RANKL neutralisation prevents osteoclast activation in a human in vitro ameloblastoma-bone model
No full textSupplemental material, sj-docx-1-tej-10.1177_20417314221140500 for RANKL neutralisation prevents osteoclast activation in a human in vitro ameloblastoma-bone model by Judith Pape, Deniz Bakkalci, Rawiya Al Hosni, Benjamin S Simpson, Kristiina Heikinheimo, Stefano Fedele and Umber Cheema in Journal of Tissue Engineering</p
Pharmacological and therapeutic studies using a bioengineered 3D breast cancer model
No full textThe breast tumour microenvironment comprises specific biophysical, biochemical, and cellular facets, which include a collagen-rich extracellular matrix and a mixture of tumour cells and stromal cells. The interactions between tumour cells and their microenvironment alter tumour behaviour and impact response to therapies. Despite their common use in breast cancer studies, in vitro 2D cell cultures exhibit limited biomimicry of breast cancer complexity. 3D cell culture models are more biomimetic as they recapitulate the physiological 3D tissue architecture of the tumour microenvironment. In this study, a biomimetic 3D in vitro breast tumour model, termed ‘tumouroid’, was developed by incorporating breast tumour cells within a complex stroma to mimic the physiological tumour microenvironment. This model was used to investigate the therapeutic effects of targeted nano-delivery systems, combined ultrasound with chemotherapy and photodynamic therapy in the treatment of breast cancer.
A novel 3D multi-compartment dense collagen I gel was engineered, where either MCF-7 or MDA-MB-231 breast cancer cells were embedded within a central artificial tumour mass surrounded by a stromal compartment composed of stromal cells with various extracellular matrix proteins. The impact of the stromal compartment on cancer cell growth and invasion, along with changes in oxygen levels, was evaluated in 3D tumouroids. The response to different therapies, including doxorubicin, liposomal doxorubicin, hyaluronic nanoparticles encapsulating doxorubicin, and photoactivatable drugs, was assessed in 3D tumouroids via imaging, cell viability assay, and real-time monitoring of oxygen gradient levels. Finally, the effect of ultrasound application on the uptake of previously drug-treated tumouroids was investigated.
3D breast tumouroids were successfully established where the presence of adipose tissue-derived mesenchymal stem cells and extracellular matrix proteins in the stromal compartment influenced vascular network formation, hypoxia development, cancer cell growth, invasion, as well as response to therapies. The stromal compartment significantly enhanced the tumourigenic potential of the less metastatic MCF-7 breast cancer cells compared to the highly metastatic MDA-MB-231. Direct killing of tumour cells was observed in addition to disruption of vascular networks and alleviation of hypoxia, in response to doxorubicin, hyaluronic nanoparticles encapsulating doxorubicin, and combined doxorubicin/photoactivatable drug treatments. MCF-7 breast cancer cells showed higher drug therapeutic responses compared to MDA-MB-231 breast cancer cells. Ultrasound application improved the cell-killing effects of doxorubicin and liposomal doxorubicin in MDA-MB-231 3D tumouroids.
In conclusion, 3D breast tumouroids display biomimicry of the in vivo breast tumour microenvironment and the ability to distinguish between different drug responses, which support their suitability as a platform for mechanistic studies of tumour biology and therapeutic screening.
Development and characterisation of 3D skeletal muscle constructs under defined mechanical regulation
No full textEThOS - Electronic Theses Online ServiceGBUnited Kingdo
Oxygen consumption rate of cells in 3D culture: The use of experiment and simulation to measure kinetic parameters and optimise culture conditions
No full textMultiple Long-Term Conditions (MLTC) and the Environment: A Scoping Review
No full textBackground: Multiple Long Term conditions (MLTC) are a major health care challenge associated with high service utilisation and expenditure. Once established, the trajectory to an increased number and severity of conditions, hospital admission, increased social care need and mortality is multifactorial. The role of wider environmental determinants in the MLTC sequelae is unclear. Aim: the aim of this review was to summarise and collate existing evidence on environmental determinants on established MLTC. Methods: comprehensive search of Medline, Embase, Cochrane, CINAHL and Bielefeld Academic Search Engine (BASE), from inception to 4th June 2022 in addition to grey literature. Two authors independently screened and extracted papers. Disagreements were resolved with a third author. Results: searches yielded 9079 articles, 12 of which met the review’s inclusion criteria. Evidence of correlations between some environmental determinants and increased or decreased risks of MLTC were found, including the quality of internal housing/living environments, exposure to airborne environmental hazards and a beneficial association with socially cohesive, accessible and greener neighbourhood environments. Conclusions: The majority of the 12 included papers focused on the built and social environments. The review uncovered very limited evidence, indicating a need for further research to understand the role of environmental determinants in MLTC
Enhancing the Mechanical Properties of 3d Biomimetic Type I Collagen Scaffolds Using Restricted Plastic Compression for Musculoskeletal Engineering
No full text
Evolution of oxygen utilization in multicellular organisms and implications for cell signalling in tissue engineering
No full textOxygen is one of the critically defining elements resulting in the existence of eukaryotic life on this planet. The rise and fall of this element can be tracked through time and corresponds with the evolution of diverse life forms, development of efficient energy production (oxidative phosphorylation) in single cell organisms, the evolution of multicellular organisms and the regulation of complex cell phenotypes. By understanding these events, we can plot the effect of oxygen on evolution and its direct influence on different forms of life today, from the whole organism to specific cells within multicellular organisms. In the emerging field of tissue engineering, understanding the role of different levels of oxygen for normal cell function as well as control of complex signalling cascades is paramount to effectively build 3D tissues in vitro and their subsequent survival when implanted
Photobiomodulation therapy (PBMT) in skeletal muscle regeneration: A comprehensive review of mechanisms, clinical applications, and future directions
No full textPhotobiomodulation therapy (PBMT) emerged as a significant non-invasive method of stimulating regeneration of the skeletal muscle tissue. This review considers the pathophysiologic and molecular mechanisms of muscle repair, with a focus on the imperative of inflammation resolution, activation of satellite cells, mitochondrial ATP generation, and angiogenesis, with consideration of the role of PBMT.We systematically evaluate preclinical and clinical studies, highlighting the translational gaps caused by differences between controlled experimental models and the complex, heterogeneous nature of human muscle injuries. Variability in PBMT parameters—such as wavelength, fluence, and pulse mode—and the lack of standardized protocols are identified as major barriers to consistent therapeutic outcomes.Furthermore, we discuss the effects of PBMT in acute and chronic muscle injury models and provide an in-depth analysis of laser parameters to elucidate dose-response relationships.Future directions for research involve the application of real-time biofeedback devices, the utilization of artificial intelligence-based individualized therapeutic approaches, as well as the integration of photobiomodulation therapy with nanotechnology, biomaterials, and multiple mechanical stimulation methods.In concusion, while PBMT has significant potential for muscle regeneration therapies, its clinical application requires more complete mechanistic validation, rigorous standardization, and interdisciplinary technological development
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