Current Research SinceCaroline has been working in peripheral nerve repair, characterising blends of biodegradable polymers for use in nerve tissue Engineering.
They provide convenient models to tackle some of the key issues in the preclinical development of novel diagnostic technologies for oral cancer and oral dysplastic lesions.
Here, we assess the ability of the pH-sensitive poly 2- methacryloyloxy ethyl phosphorylcholine PMPC - poly 2- diisopropylamino ethyl methacrylate PDPA polymersomes to Vanessa hearnden thesis chemotherapeutic agents for effective combinational anticancer therapy. Multi-cellular tumour spheroids were created from an oral cancer cell line to model solid expanding tumour masses.
More targeted treatments for oral cancer are also needed which can be administered to the site of disease with higher efficiency and accuracy to reduce side effects and allow higher concentrations of therapeutic agents to be delivered to tumour cells. In addition, we explored the potential of polymersomes to cross the oral epithelial permeability barrier and act as delivery vehicles for topical delivery of therapies for oral mucosal diseases and as an alternative to parenteral administration for the systemic delivery of drugs.
Results showed good penetration of polymersomes into the oral mucosa and the multi-cellular tumour spheroids demonstrating the potential to develop these drug delivery vehicles to deliver anti-cancer drugs and other therapeutic agents in the future.
The tissue engineered models of oral mucosa and the multi-cellular tumour spheroids were used to test the behaviour of polymersomes, a novel drug delivery system, in three dimensional tissues.
Drug delivery agents that are able to reach the central hypoxic region of solid expanding tumours are particularly important as these cells are often resistant to both radio- and chemotherapy and correlate with poor patient prognosis. Early detection could reduce these mortality rates but unfortunately diagnosing oral cancer, which is often symptomless, in the early stages of the disease is incredibly challenging.
In monolayer culture, only a short exposure to drug-loaded polymersomes was required to elicit a strong cytotoxic effect. These oral cancer models incorporated many pathological features of oral cancer progression including features seen in dysplastic epithelia, carcinoma in situ and early invasive squamous cell carcinomas.
Caroline has used 3D microfabrication techniques, such as microstereolithography and electospinning, to fabricate Nerve guide conduits, and internal scaffolds for nerve guidance.
Caroline has also investigated the use of aminosilanes, as a coating to aid peripheral nerve repair, which is to be published soon. Doxorubicin and paclitaxel were encapsulated into pH-sensitive PMPC-PDPA polymersomes with high efficiencies either in isolation or as a dual-load for both singular and combinational delivery.
There is a need for both better detection and treatment. The results obtained from these different techniques showed varying degrees of promise with the images from OCT demonstrating that this technology has real diagnostic potential.
Whilst working, Caroline has also done her PhD full time in Peripheral Nerve repair and Nerve Tissue Engineering, working in the Haycock research Group, and is due to submit her thesis in the next month. Polymersome uptake and ability to deliver encapsulated drugs into healthy normal oral cells and oral head and neck squamous cell carcinoma HNSCC cells was measured in two and three-dimensional culture systems.
Polymersome cellular uptake was found to be mediated by class B scavenger receptors. We also observed that these receptors are more highly expressed by cancer cells compared to normal oral cells, enabling polymersome-mediated targeting.
The 3D models proved useful test-beds for some but not all of these diagnostic imaging techniques. Caroline has been supervised by Professor John W.
This has involved in vitro testing titanium Scaffolds, using primary human osteoblasts, for use in Bone tissue Engineering applications. These included a cell metabolism marker, impedance spectroscopy, Fourier transform infra-red and optical coherence tomography. When delivered to three-dimensional tumor models, PMPC-PDPA polymersomes were able to penetrate deep into the center of the spheroid resulting in extensive cell damage when loaded with both singular and dual-loaded chemotherapeutics.
This project used a tissue engineered oral mucosa model to develop models of oral cancer progression. The tissue engineered models of cancer were next utilised to test four non-invasive diagnostic technologies.
Samples underwent physical characterisation and chemical characterisation, and in vitro testing was performed using NG neuronal cells, primary Schwann cells and Dorsal root ganglion ex vivo culture.
Despite advances in surgery and therapy the survival rates for those diagnosed with oral cancer have not significantly improved over the past 20 years. Moreover, the preferential internalization of PMPC polymersomes by exploiting elevated scavenger receptor expression on cancer cells opens up the opportunity to target polymersomes to tumors.Vanessa Hearnden ultimedescente.com Member.
UPLOADS. POSTS. Hearnden, Vanessa () Developing tissue engineered models of oral mucosa and oral cancer to study novel therapeutic and diagnostic techniques.
PhD thesis, University of Sheffield. This list was generated on Mon Sep 3 BST. Vanessa Hearnden, The University of Sheffield, Depertment of Material Science and Engineering Department, Faculty Member.
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Vanessa Hearnden joined the Department of Materials Science and Engineering in as Lecturer in Biomaterials and Tissue Engineering. Vanessa’s undergraduate degree was in Biomedical Science; she then obtained her PhD in Tissue Engineering from the University of Sheffield inDownload