3-D acini models of oral epithelial dysplasia
The epithelium represents a major class of tissue architecture with unique functions. It serves as a regulator of mass transport, defense against pathogens, and source of mucosal extracellular matrix (ECM). Dysregulation of the normal turnover of epithelial cells has been associated with several chronic diseases, including fibrosis and cancer. The current gold standard for studying epithelium function in vitro is the transwell culture. However, the lack of physiologically relevant dimensional cues and mismatched material properties between cells and polymer membranes can lead to unnatural epithelium morphologies and functions. Our proposed solution is to use 3-D epithelial acini (i.e., well-organized and polarized spherical epithelial structures) as a long-term and physiologically relevant epithelium model. Currently we are using this platform to model epigenetic and metabolic changes in during epithelial dysplasia, which characterized by progressive tissue disorganization and is the precursor to oral cancer. The goal is to understand the pathways and biomarkers present in the early stage of oral cancer progression, so that better diagnostic tests and treatments can be developed. This model will also be broadly useful in modelling other epithelial tissues in the airway and digestive track.
Bio-printed human-microbe co-cultures
Human beings live alongside a vast variety of microorganisms in the environment, many of which reside within us and in direct contact with our mucosal epithelium (e.g oral, airways and gut). Recent research has highlighted the associations between microbes and human health, from metabolic diseases to cancers. However, little is known about the mechanisms of these interactions due to the lack of translatable in vivo and in vitro models. To date, few in vitro systems are able to directly co-culture human cells and microbes in a defined and repeatable fashion. Our group aims to address this problem by using advanced bio-printing techniques and specially formulated bio-ink to confine bacterial colonies in direct co-culture with engineered human tissues (see project 1). In an earlier study we have successfully cultivated bacteria biofilm on an epithelial cell monolayer using an aqueous two-phase system (ATPS). The goal here is to expand on this concept to create long-term, multiplexed bacteria colonies on a 3-D epithelium model to study human microbiome related diseases.
In vitro models of tumour microenvironment
Over the course of tumour development, its microenvironment becomes increasingly depleted in nutrients (glucose, oxygen etc.) due to poor mass transport. In response, tumour cells develop a variety of coping mechanisms, including altered metabolic and signalling pathways. One strategy to combat tumours is by interrupting these survival mechanisms. This can be achieved by sustained local release of therapeutics in the tumour microenvironment. To this end, degradable bioactive glass material capable of releasing therapeutic inorganic ions (TII) presents a unique intervention modality. In collaboration with Dr. Daniel Boyd we aim to develop novel TII-glass compositions that can 1) interfere with tumour-specific metabolic pathways, and 2) abolish tumour permissive phenotypes of local immune cells (macrophages and dendritic cells). These materials may have the potential to augment current anti-cancer treatment regimes or be used as standalone therapeutic options.
Biomaterial Design for regenerative endodontic therapy
Endodontic therapy, or commonly known as root canal therapy, is a standard procedure for treating infected pulp by replacing living pulp tissue with inert filling material. However, the loss of living pulp tissue prevents future growth and development of the dentinal wall, and this is particularly problematic for young patients as it leads to weak tooth and increase chances of fracture. Recently, regenerative endodontic therapy based on revascularization has gain traction as a promising option to restore dentin development. The technique relies on the formation of a blood clot in the root canal space to act as a provisional scaffold by mechanically inducing bleeding from the root. However, controlled formation of blood clot in situ is difficult, which may lead to unpredictable results. In collaboration with Dr. Isabel Mello (Dalhousie) we are developing novel biomaterials to guide the formation of blood clot and to assist the migration of stem cells of the apical papilla (SCAP) into the root canal. We are exploring the of 3-D bioprinting technology to deliver cell migration cues and differentiation cues directly into the structure of biomaterials to direct SCAP function within the root canal. In addition, we are building in vitro models of the root canal to better understand the transport kinetics of antimicrobial antiseptic agents and to investigate their roles in SCAP survival.