Biomimetic 3D scaffold for cancer research

Abstract

Cancer is a leading cause of death around the world in recent years. Tissue engineering and Materials Science are important tools in cancer research in the fields of basic pathology, drug discovery and radiation oncology. This project involved the development of a biomimetic three-dimensional (3D) model based polycaprolactone (PCL) that was biocompatible and biodegradable for cancer cells. Such a scaffold would have significant advantages compared to traditional 2D models in mimicking the in vivo tumour microenvironment as tumours are 3D structures. An aliphatic composite scaffold concept was adopted and the scaffold composition was modified to improve cancer cell growth. The development of the synthetic scaffold (extracellular-matrix analogue) which demonstrated superior scaffold design flexibility as well as reproducibility was compared to naturally-derived counterparts. Bioactive glass is a synthetic biomaterial and commonly used in tissue replacement. Bioactive glass scaffold dopant was incorporated to enhance tissue formation and was a stimulant to improve cell growth in the polymeric scaffold. Bioactive glass 45S5 was incorporated into the scaffold by coating, infusion and coating with PCL sizing (extremely thin encapsulation). Pre-soaking of scaffolds by culture medium was a second promoting factor that was explored. In vitro cell growth (Melanoma and bowel cancer cell lines) on bioactive glass implanted scaffolds was compared to non-modified scaffold and scaffolds with collagen coating (natural material) and quantified with haemocytometry and protein assay. In composition modification, non-supplemented medium pre-soaking represented a promoting effect on cell adsorption. Advanced sized bioactive glass coated scaffold with non-supplemented medium pre-soaking demonstrated the highest capability in proliferating cells compared to other synthetic and natural modifications. Cell proliferating capability of bioactive glass was promoted 6folds by PCL sizing and non-supplemented medium pre-soaking, which was an innovative strategy for in vitro tumour modelling. Scaffold pore size was important for cell growth and an optimal pore size was determined by cell size according to cell type. Interconnectivity of the pore in the scaffold was also important for tumour cell migration. The second stage of the research involved the development of a novel porosity-graded FGM (functionally graded material) PCL scaffold, fabricated by compressing wedged shape scaffolds to a pellet with even thickness. Modules were fabricated by various methods such as carving, moulding and 3D printing with several materials from metal, polymer to gel. Optimization was conducted with the view of developing a scaffold with maximum cell capture and retention capability during cell seeding of the scaffold. The FGM system was novel in tissue engineering and cancer research. FGM system was particularly useful in facilitating in vitro 3D model design as well as for study of cellular behaviours in tumour development.