Advanced Biomaterials for Tissue Engineering of Developmental Systems

The ovary is the central reproductive organ in females and provides an environment for the development of follicles, as well as producing steroid hormones, which are essential for healthy reproduction. Also, important for ovarian function is the extracellular matrix (ECM) a non-cellular component of all tissues, including the ovary, which provides structure and support for the cells. More recently it has been shown that the ECM is also involved in regulating cell behaviour, including cell division, cell death and what genes are active to produce essential proteins. Unique interactions between follicles and their ECM microenvironment direct how they develop.
Polycystic ovary syndrome (PCOS) is a reproductive disorder characterised by differing physical and biochemical features, namely elevated androgen (testosterone) levels. Evidence highlights a change in extracellular matrix morphology, and it has been suggested that the ovary is stiffer and more rigid, due to excessive collagen. This characteristic, and possible change in mechanical environment associated with the condition, may play a role in the pathogenesis of the disorder and disrupted follicle growth.
This project aims to apply the use of engineering methods and the functionalisation of biomaterials to promote tissue and follicle growth that mimics the natural environment. By understanding and characterising the natural environment, the system aims to be adaptable with the ability to match the physiology expected within the syndrome, to gain insight into the disorder.
Normal tissue mechanical dynamics have been analysed using atomic force microscopy. AFM microscopy allows you to measure the elasticity and stiffness of the environment probed. Understanding mechanical heterogeneity allows insight into how tissues and cells function. Additionally, determining whether a disease or defect is due to a perturbation in the mechanical environment.
Characterisation of the biomechanics for the ovarian environment has not been achieved, therefore a novel setup of the system has been developed and created to allow for accurate measurements. Future work will include further phenotype analysis and tissue cultures, with androgens (associated with the disorder), to measure the mechanical response.
The approach so far has created a novel set of data which will then be applied in designing a biomaterial akin to the natural environment, predominantly ECM derived. Our aim is to understand and create a normal ovarian environment in vitro. After completion of this, future work will include the testing of different materials with different mechanical properties to confirm and further understand the tissue and cellular response.
Equally the fibrotic response will be analysed using cellular gene transcription studies. The follicular response to androgens has been assessed. These results demonstrated an increase in fibrotic associated factors and a perturbed ECM response. Further validating the role of ECM and stiffness in the pathophysiology of the disorder. A crosstalk between the two approaches will allow for a thorough understanding of tissue engineering and designing the correct biomimetic system.