GOOGLE INVESTIGATION AND USE OF AN ELASTIN-LIKE PROTEIN, CONTAINING A STATHERIN DERIVED PEPTIDE SEQUENCE, TO CONTROL BIOMIMETIC FLUORAPATITE FORMATION

PhDDental enamel is an excellent example of a highly mineralised tissue, composed of hierarchically organised apatite mineral. This unique organisation gives enamel superior mechanical properties. However, when mature, enamel becomes acellular and unable to repair itself during traumatic or carious damage. The lack of self-repair requires dental intervention, where the common treatment of decayed enamel is to remove the affected and healthy tissue, and replace with restorative materials. The restorative materials, currently used, can cause further complications in the form of secondary caries or failure due to thermal and mechanical property mismatch with enamel. Problems associated with current restorative materials have driven researchers to explore biomimetic enamel treatment routes. To mimic the natural enamel formation, we can explore how proteins can guide mineral growth, in order to form enamel-like ordered mineral structures. In this thesis, the use of a synthetic, recombinant protein called an elastin-like protein (ELP) containing the analogue of the N-terminal of statherin (STNA15) was under investigation. Statherin is a protein present in saliva that is said to aid in the remineralisation of enamel. ELP with STNA15 (STNA15-ELP) has already shown promise in biomimetic mineralisation. This thesis investigated how conformation and structure of STNA15-ELP can be affected and manipulated by different chemical environments, surface constraint and crosslinking. The STNA15-ELP characteristics were related to formation of fluorapatite. STNA15-ELP conformation changed due to presence if salts in solution and whether or not it was constrained. We linked the conformational changes within STNA15-ELP, in solution versus on the surface, to two different routes of mineral formation. FAp formed in an uncontrolled manner with free STNA15-ELP. Ordered FAp formed via a precursor when STNA15-ELP was constrained on a surface. This work leads to an understanding of biomimetic mineralisation using STNA15-ELP. This information can aid in the design of novel biomimetic, enamel-like therapeutics.Life Sciences Initiative, QMUL

Elastin-Like Protein, with Statherin Derived Peptide, Controls Fluorapatite Formation and Morphology

Life Science Initiative, QMUL. The work was additionally supported by the European Research Council Starting Grant (STROFUNSCAFF) and the Marie Curie Career Integration Grant (BIOMORPH). The authors would like to acknowledge Dr. Carol Crean and Dr. Rachida Bance-Soualhi (Department of Chemistry, University of Surrey) for their help with acquiring the Raman spectroscopy data, funded by EPSRC (grant number EP/M022749/1). KS gratefully acknowledges Dr. Sherif El-Sharkawy for intellectual input and Gastón Agustín Primo for help with FTIR deconvolution, alongside other group members of the Mata, MHAtriCell and DPSU groups

Protein disorder-order interplay to guide the growth of hierarchical mineralized structures

A major goal in materials science is to develop bioinspired functional materials based on the precise control of molecular building blocks across length scales. Here we report a protein-mediated mineralization process that takes advantage of disorder–order interplay using elastin-like recombinamers to program organic–inorganic interactions into hierarchically ordered mineralized structures. The materials comprise elongated apatite nanocrystals that are aligned and organized into microscopic prisms, which grow together into spherulite-like structures hundreds of micrometers in diameter that come together to fill macroscopic areas. The structures can be grown over large uneven surfaces and native tissues as acid-resistant membranes or coatings with tuneable hierarchy, stiffness, and hardness. Our study represents a potential strategy for complex materials design that may open opportunities for hard tissue repair and provide insights into the role of molecular disorder in human physiology and pathology

Topographically guided hierarchical mineralization

Material platforms based on interaction between organic and inorganic phases offer enormous potential to develop materials that can recreate the structural and functional properties of biological systems. However, the capability of organic-mediated mineralizing strategies to guide mineralization with spatial control remains a major limitation. Here, we report on the integration of a protein-based mineralizing matrix with surface topographies to grow spatially guided mineralized structures. We reveal how well-defined geometrical spaces defined within the organic matrix by the surface topographies can trigger subtle changes in single nanocrystal co-alignment, which are then translated to drastic changes in mineralization at the microscale and macroscale. Furthermore, through systematic modifications of the surface topographies, we demonstrate the possibility of selectively guiding the growth of hierarchically mineralized structures. We foresee that the capacity to direct the anisotropic growth of such structures would have important implications in the design of biomineralizing synthetic materials to repair or regenerate hard tissues