Thesis

3D biofabrication of constructs for orthopaedic tissue regeneration and clinical biofilm study

Creator
Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2022
Thesis identifier
  • T16405
Person Identifier (Local)
  • 201676349
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • The rising prevalence of arthritis and osteochondral defects (OCDs) has led to growing worldwide demand for joint replacement surgery. Meanwhile, the prevalence of antimicrobial resistance (AMR) and prosthetic joint infections (PJIs) in clinical orthopaedics is growing at alarming pace. A novel approach to help tackle AC defects and AMR alike is offered by 3D biofabrication, as a technology with the capacity to deposit cells, bacteria and biomaterials in user-defined patterns to build 3D constructs from the “bottom-up.” Initially composite AlgMA/Col and AlgMA/GelMA bioinks were developed and combined with a novel triple-crosslinking approach (double ionic and UV) following extrusion FRESH (freeform reversible embedding of suspended hydrogels) bioprinting to allow creation of 1mm thick constructs. Constructs maintained shape in culture over 28 days, whilst stability was improved with addition of AlgMA (p<0.05). High chondrocyte and MSC viability was achieved following bioprinting (>95%) with accelerated cell growth demonstrated with inclusion of cell spheroids (p<0.05). The prolonged stability and cell viability seen outperformed many commercially available bioinks. The composite bioinks were also successfully injected into in vitro OCDs and crosslinked in situ, with cell viability and 3D integrity of OCD patches maintained over 14-days. Focussing on AMR, a biocompatible ionically cross-linked bacterial bioink was also developed that allowed precise 3D bioprinting of bacterial structures that developed clinically relevant, mature 3D biofilms during culture. Further analysis of 3D biofilms allowed antimicrobial penetration and the biofilm lifecycle to be observed in 3D. The 3D biofilms were also utilised to allow development of a novel Raman spectroscopy technique, that allowed detection of bacterial biofilms within a joint infection model. In summary, we hope that our findings show potential for a new approach to the regeneration of AC defects, progress the investigation of 3D biofilm formation and AMR, and finally show a new approach to diagnosis of joint infection.
Advisor / supervisor
  • Shu, Will
Resource Type
DOI

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