The European Ceramic Society
YCN Research in the Spot : Effect of silicon substitution in calcium phosphates on blood vessel formation by Else Ellermann
YCN Newsletter 11 - December 2021
As a fourth-year PhD student at the Cambridge Centre of Medical Materials, I have dived into the topic of tissue regeneration. Bone tissue engineering, specifically, aims to regenerate bone using a degradable construct similar in composition to the body’s own material. Ultimately, the so-called scaffold should stimulate the host to successfully heal a critical-size fracture or bone void. Synthetic hydroxyapatite (HA) closely mimics the mineral component of bone, making it an attractive material for orthopaedic surgery and, over the years, studies have assessed ways to improve the biological response incited by the biomaterial. As bone is known to naturally contain various ions, much research has focussed on ion substitution into the HA lattice. Silicon substitution, in particular, has shown promising results, inducing enhanced bone mineralisation, mechanical stability and bone cell (osteoblast) attachment and proliferation. However, a major challenge in this field remains the development of an interconnected blood vessel network into the construct, enabling nutrient and waste exchange to prevent core degradation of the graft. To date, a few studies have shown successful conduction of blood vessels on silicon-substituted HA (Si-HA) surfaces and improved vessel growth compared with HA in in vitro monocultures. While monocultures can be useful for assessing the direct response of one cell type to certain surface properties without the interference of other cell types, heterotypic cell-cell contact, as will occur in vivo, will ultimately alter their response. In vitro co-culturing of different cell types has been found to result in one of the cell types stimulating its counterpart to proliferate, differentiate, survive and produce certain growth factors. Therefore, more in-depth knowledge of simultaneous growth of endothelial cells (for blood vessel formation) and bone cells in response to Si-HA is needed to enable optimisation of the surface properties of the graft to suit both cell types.
At the Cambridge Centre of Medical Materials, we specialise in engineering biomedical devices and assessing biological tissue for the purpose of tissue engineering. Calcium phosphates as a scaffold material for bone regeneration is one of the versatile topics studied in this lab. My research, specifically, aims to establish the optimal experimental parameters for promoting in vitro formation of vessel-like structures to assess the effect of silicon substitution in calcium phosphates on blood vessel formation. Sequential seeding of osteoblasts (OBs) and endothelial cells (ECs) at an OB to EC cell ratio of 70:30 without external stimuli, was found to induce a more complex vessel-like network on Si-HA as opposed to HA in a 2D environment (see Figure). Furthermore, since it has been proven difficult to assess the direct effects of silicon on cell behaviour, as the ion substitution simultaneously changes the electrochemical and physical properties of HA, a novel method is tested and applied to deconvolute between these surface properties. Obtaining reliable knowledge on the extent to which each property influences the bioactivity of Si-HA would allow future studies to make informed decisions regarding the optimisation of scaffold properties, to ultimately improve bone tissue engineering outcomes.
Figure: Fluorescent images of Si-HA and HA discs co-cultured with an OB:EC cell ratio of 70:30 (scale bar indicates 150 µm). Red: CD31 staining, Blue: DAPI nuclei staining, Green: von Willebrand Factor.
Cambridge Centre of Medical Materials
University of Cambridge
Email Address: Ee310@cam.ac.uk
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