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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
first_indexed 2023-03-17T12:56:06Z
last_indexed 2024-11-15T18:00:40Z
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recordtype RisThesis
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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. 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spelling 2024-04-22T15:27:16.4227042 v2 62975 2023-03-17 Development of a Novel Composite Bioink for Cartilage Tissue Engineering 57856a56b812b74d91a61a923fef2217 THOMAS JOVIC THOMAS JOVIC true false 2023-03-17 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. E-Thesis Swansea Biomaterials, 3D Printing, nanocellulose, facial reconstruction 5 1 2023 2023-01-05 10.23889/SUthesis.62975 COLLEGE NANME COLLEGE CODE Swansea University Whitaker, Iain S,; Doak, Sharren H. Doctoral Ph.D Action Medical Research and VTCT Foundation Clinical Research Training Fellowship, Royal College of Surgeons England Clinical Research Fellowship, BAPRAS Paton Masser Award Action Medical Research and VTCT Foundation Clinical Research Training Fellowship, Royal College of Surgeons England Clinical Research Fellowship, BAPRAS Paton Masser Award GN2782 2024-04-22T15:27:16.4227042 2023-03-17T12:00:49.5891350 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine THOMAS JOVIC 1 62975__26880__57cbebfc89a14b219f8083d82258da61.pdf Development of a Novel Composite Bioink for Cartilage Tissue Engineering_Redacted.pdf 2023-03-17T12:49:45.5138624 Output 29743915 application/pdf E-Thesis – open access true 2024-04-01T00:00:00.0000000 Development of a Novel Composite Bioink for Cartilage Tissue Engineering © 2022 by Thomas Harry Jovic is licensed under CC BY 4.0 true eng https://creativecommons.org/licenses/by/4.0/?ref=chooser-v1
title Development of a Novel Composite Bioink for Cartilage Tissue Engineering
spellingShingle Development of a Novel Composite Bioink for Cartilage Tissue Engineering
THOMAS JOVIC
title_short Development of a Novel Composite Bioink for Cartilage Tissue Engineering
title_full Development of a Novel Composite Bioink for Cartilage Tissue Engineering
title_fullStr Development of a Novel Composite Bioink for Cartilage Tissue Engineering
title_full_unstemmed Development of a Novel Composite Bioink for Cartilage Tissue Engineering
title_sort Development of a Novel Composite Bioink for Cartilage Tissue Engineering
author_id_str_mv 57856a56b812b74d91a61a923fef2217
author_id_fullname_str_mv 57856a56b812b74d91a61a923fef2217_***_THOMAS JOVIC
author THOMAS JOVIC
author2 THOMAS JOVIC
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publishDate 2023
institution Swansea University
doi_str_mv 10.23889/SUthesis.62975
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description 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.
published_date 2023-01-05T05:07:17Z
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