Synergistic coatings to control stem cell fate

A major field of research in regenerative medicine is the process of replacing or repairing tissues and tissue function by the implantation of modified cells grown on a suitable artificial biomaterial. Specific functionality and viability is required of the implanted cells to correctly emulate the host tissue in-situ and this is regulated by their growth and implantation environment1. Within tissues cells are surrounded by a complex 3D extracellular matrix (ECM) which regulates both cell viability and differentiation state. Cellular ECMs can vary in chemical and physical properties that in turn alter the growth and activity of the cells they encompass. Research has shown that without the structural support and biochemical signalling provided by the ECM, cells become de-differentiated and lose viability making them unsuitable for tissue engineering purposes. Due to these issues different bioreactor and synthetic support scaffold approaches have been developed to emulate the ECM in-vitro. These studies have shown that with the addition of key proteins, a degree of the physical and chemical functions as found in-situ can be maintained and developed in-vitro. These advancements in biomimetics have developed more sustainable cellular populations which maintain differentiation states for longer. In order to optimise this system for tissue engineering treatments; development of synthetic scaffolding to grow and implant cells within, that possess the ability to more accurately simulate the chemical and physical environment found within in-situ tissues is needed. This research aims to examine in-depth the sole relationship individual ECM proteins have with determining cell fate when expressed on a rigid polymer biomaterial. One protein indicated to having a critical role in cellular interactions within the ECM is Fibronectin (FN). Studies have found that the exclusion of FN from a cells ECM can cause developmental embryonic lethality1, 2, possibly due to a loss of regulation of cell fate suggesting a potential role in stem cell differentiation. In mature cells this structural protein has been shown to control many cellular functions including; adhesion, migration, differentiation and growth 3, these vital ECM-cell interactions make this protein a prime candidate for biomimetic studies. Fibronectin is mainly found as dimers within tissue, in either an active fibril conformation which allows for the majority of its alternatively spliced binding sites to interact or in a globular inactive form. To stimulate in-vivo functionality of FN a suitable adsorption medium must be used to express the protein. Research has shown that adsorption of fibronectin onto synthetic polymer surfaces can induce cellular interactions which maintain viability and function of in-vitro cell cultures 4. Current studies 1,4 utilising synthetic polymers as a scaffold for FN, for example poly ethyl acrylate (PEA), have shown the ability to direct the formation and organisation of FN fibrils. This allows for PEA to adsorb and maintain active FN proteins which in turn can regulate cellular functions, emulating aspects of in-vivo ECM.