The characterisation of adipose derived stem cells on coralline scaffolds for bone tissue engineering
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Skeletal injuries affect millions of people worldwide, making it one of the most common causes of severe chronic pain and physical disability while also being a heavy burden on Australian healthcare, costing approximately $700 million a year. Over the past decades, biodegradable coralline biomaterials have been considered as an alternative implant material for bone regenerative therapy. This is because coralline materials have been found as being clinically advantageous due to their biocompatibility, osteoconductivity and scaffold resorbability. Additionally, coating coralline material with autologous stem cells is desirable for tissue ingrowth to occur rapidly as possible to provide the implant with structural integrity and eventual complete scaffold resorption. Adipose Derived stem cells (ADSCs) are considered promising biological tools for regenerative medicine as they are an accessible and abundant source of stem cells that have shown to be able to differentiate into bone tissue. Recent in vivo and in vitro studies of coralline materials seeded with mesenchymal stem cells have produced conflicting results that range from demonstrating complete fracture repair to ineffective tissue regeneration. This is because the underlying biological mechanism behind the clinically advantageous properties of coralline material is not well understood. This PhD project has therefore been developed in order to address the problems outlined above. This work has investigated the effect of seeding rat adipose derived stem cells (rADSCs) and human adipose derived stem cells (hADSCs) onto biomimetic coralline scaffolds. The data presented here demonstrates that ADSCs can be successfully cultured onto coralline scaffolds, which provide a suitable microenvironment for ADSCs to proliferate. Additionally, the research I have undertaken shows that ADSCs seeded on coralline scaffolds undergo a proteomic change that resembles osteogenic cells, without the addition of any external osteoinductive factors. This project also investigated the effects of different coralline scaffolds such as coralline carbonate, converted coralline hydroxyapatite (cHA), nanoporous cHA, macroporous cHA and high-density cHA on hADSCs where I showed that seeded cHA induced a stronger osteogenic response than seeded coralline calcium carbonate. Furthermore, I identified a unique immunomodulatory response from each seeded coralline scaffold that suggested a microenvironment rich in pro-inflammatory and pro- angiogenic factors which is a physiological feature commonly noted during in vivo fracture repair. Overall this PhD project has contributed significantly to a wealth of biological knowledge about the effects of coralline scaffolds on ADSCs. Future work can utilise what is described here to either fabricate a coralline implant to harness the biological responses we have recorded or apply the data towards a safe and effective animal model for future therapeutic applications.
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