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Development of a Novel Composite Bioink for Cartilage Tissue Engineering / THOMAS JOVIC

Swansea University Author: THOMAS JOVIC

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DOI (Published version): 10.23889/SUthesis.62975

Abstract

SummaryIntroduction and aims: Nanocellulose bioinks have promising biological andmechanical properties for 3D bioprinting. The aim of this thesis was to developa novel natural composite biomaterial derived of nanocellulose to bioprint withcartilage derived cells for ear reconstruction.Methods: Carti...

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Published: Swansea 2023
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
Supervisor: Whitaker, Iain S,; Doak, Sharren H.
URI: https://cronfa.swan.ac.uk/Record/cronfa62975
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Abstract: SummaryIntroduction and aims: Nanocellulose bioinks have promising biological andmechanical properties for 3D bioprinting. The aim of this thesis was to developa novel natural composite biomaterial derived of nanocellulose to bioprint withcartilage derived cells for ear reconstruction.Methods: Cartilage derived cells were extracted from nasoseptal cartilage andchondroprogenitor cells were isolated using fibronectin adhesion assay.Different combinations of progenitor cells and chondrocytes were created todetermine the most chondrogenic combination for 3D bioprinting cartilage.Nanocellulose blend, crystal and fibrils were blended with alginate andcompared for printability and chondrogenicity profiles. The most chondrogenicand printable formulation was then mixed with varying proportions ofhyaluronic acid to produce composite bioinks. Human nasoseptalchondrocytes from at least 3 separate patients were cultured in the compositebiomaterial, and crosslinking with low dose hydrogen peroxide was optimised.Chondrogenicity was determined with PCR, quantitative protein assays andhistology. Printability was assessed using rheology and printing assays.Mechanical properties were examined using atomic force microscopy andcompression testing. Biocompatibility was demonstrated with Live-Dead,lactate dehydrogenase and alamarBlue assays.Conclusions: There were no benefits to combining cells isolated with thefibronectin assay compared to using native cartilage cell populations,indicating an inadequacy with the validity of this assay in nasoseptal cartilage.All nanocellulose materials demonstrated superior printability andbicompatibilty to alginate, with crystals and blend varieties offering superiorbiological properties. Instant crosslinking of the nanocellulose-hyaluronic acidbioinks were achievable with no detriment to cell survival. Nanocellulosehyaluronic acid bioink was more chondrogenic than nanocellulose-alginateand hyaluronic acid alone. Cell viability and proliferation was sustained over21 days. Nanocellulose-hyaluronic acid bioinks demonstrate superiorchondrogenicity, favourable mechanical properties and excellentbiocompatibility for bioprinting cartilage for reconstructive surgery. These inkshold promise for in vivo testing and eventually clinical translation.
Keywords: Biomaterials, 3D Printing, nanocellulose, facial reconstruction
College: Faculty of Medicine, Health and Life Sciences
Funders: Action Medical Research and VTCT Foundation Clinical Research Training Fellowship, Royal College of Surgeons England Clinical Research Fellowship, BAPRAS Paton Masser Award