Regenerative biomaterials for maxillofacial applications

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Arthroscopic surgical procedures aiming to regenerate maxillofacial tissues are troubled by its complex structures and challenging surgical access. Indeed, while minimal invasive procedures that deliver regenerative materials and/or cells are common in articulating joints such as the knee, there are currently no standardised treatments that place cells, regenerative factors or materials into maxillofacial tissues to foster bone, cartilage or muscle repair. This project aimed to develop hyaluronic acid (HA)-based hydrogels, which are suitable for use in minimally invasive procedures, that can adhere to the surrounding tissue, and deliver cells and drugs. Consequently, cells produce cartilage-specific extracellular matrix (ECM) components to replace the hydrogel with, resulting in neo-tissue. This effect might be further increased by introduction of Dimethyloxalylglycine (DMOG).

Modifying HA with both methacrylate (MA) and 3,4-dihydroxyphenylalanine (Dopa) groups using a completely aqueous synthesis route, MA-HA-Dopa hydrogels can be applied under aqueous conditions, gel quickly using a standard surgical light, and adhere to tissue. Moreover, upon oxidation of the Dopa, human marrow stromal cells (hMSC) attach to hydrogels and survive when encapsulated within them. In order to assess the formation of extracellular matrix components, non-canonical amino-acid tagging (FUNCAT) with Raman spectral imaging have been utilised. Combining those, 3D spectral and fluorescence maps of cells and their secreted ECM allow qualitative and quantitative analysis. FUNCAT and Raman are unbiased, inexpensive and rapid techniques. Results show peptides/proteins being secreted, with them accumulating in the immediate space around the plasma membrane. Depending on the hydrogel formulation, DMOG did increase quantity as well as distance of newly synthesised peptides/proteins being detected away from the cell membrane. The overall findings suggest that MA-HA-Dopa hydrogels may find use in minimally invasive procedures to foster maxillofacial tissue repair.
Date of Award1 Oct 2020
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorEileen Gentleman (Supervisor) & Kathy Fan (Supervisor)

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