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Manufacturing and assessment of osteogenically enhanced hydroxyapatite/ calcium carbonate bone scaffolds / EMMA STEIJVERS

Swansea University Author: EMMA STEIJVERS

Abstract

Bone grafts are essential for repairing large bone defects, but natural sources are scarce and alternatives are needed. Hydroxyapatite/calcium carbonate scaffolds are osteocompatible and resorbable and thus suitable for bone grafts, but lack the growth factors and related osteogenicity present in na...

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Published: Swansea, Wales, UK 2023
Institution: Swansea University
Degree level: Master of Research
Degree name: MSc by Research
Supervisor: Xia, Zhidao., Deganello, Davide. and Khan, Ilyas.
URI: https://cronfa.swan.ac.uk/Record/cronfa64629
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first_indexed 2023-09-27T13:57:01Z
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spelling v2 64629 2023-09-27 Manufacturing and assessment of osteogenically enhanced hydroxyapatite/ calcium carbonate bone scaffolds 0b8e2c94c5ea2b8bc99f5cdaea16883f EMMA STEIJVERS EMMA STEIJVERS true false 2023-09-27 Bone grafts are essential for repairing large bone defects, but natural sources are scarce and alternatives are needed. Hydroxyapatite/calcium carbonate scaffolds are osteocompatible and resorbable and thus suitable for bone grafts, but lack the growth factors and related osteogenicity present in natural grafts. This study aimed to enhance the osteogenic capacity of these bone scaffolds through two methods: 1) culturing and osteogenically differentiating mesenchymal stem cells onto the scaffolds in vitro so that they generate and deposit growth factors, and adding retinoic acid to increase cell differentiation and bone morphogenic protein expression, and 2) adding bisphosphonates, anti-osteoporotic medication, to the scaffolds to inhibit bone resorption and maximize the initial bone growth. Cell growth on scaffolds in vitro was analysed using fluorescence and scanning electron microscopy and metabolic assays, and growth factors were quantified using ELISA. The results indicate that MSCs grow and deposit BMPs onto the scaffolds. Osteogenic differentiation increased the amount after 14, but not 7 or 21 days of culture, while the addition of RA is detrimental to growth factor production. The effect of bisphosphonates was determined by implanting scaffolds treated with OX-14 and Zoledronate in vivo in mice, then quantifying the bone growth through μCT scanning and the gene expression using qPCR. The addition of Zoledronate, but not OX-14, increased the bone callus size at all time points. In conclusion, both approaches are promising methods to improve bone scaffold osteogenicity. Culturing cells onto scaffolds can be done to add growth factors to them, though future research should aim to increase the amount deposited. The addition of Zoledronate increases bone callus size, and future research should determine the effectiveness of this approach in critical-sized bone defects. E-Thesis Swansea, Wales, UK Bone scaffolds, hydroxyapatite, bone cement, bone implant 27 9 2023 2023-09-27 COLLEGE NANME COLLEGE CODE Swansea University Xia, Zhidao., Deganello, Davide. and Khan, Ilyas. Master of Research MSc by Research 2023-09-27T14:59:29.4359575 2023-09-27T14:54:01.3400367 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science EMMA STEIJVERS 1 64629__28646__079e9a15c9974bae8616abda63a33b70.pdf 2023_Steijvers_E.final.64629.pdf 2023-09-27T14:57:15.4736301 Output 3145614 application/pdf E-Thesis true Copyright: The Author, Emma Steijvers, 2023. true eng
title Manufacturing and assessment of osteogenically enhanced hydroxyapatite/ calcium carbonate bone scaffolds
spellingShingle Manufacturing and assessment of osteogenically enhanced hydroxyapatite/ calcium carbonate bone scaffolds
EMMA STEIJVERS
title_short Manufacturing and assessment of osteogenically enhanced hydroxyapatite/ calcium carbonate bone scaffolds
title_full Manufacturing and assessment of osteogenically enhanced hydroxyapatite/ calcium carbonate bone scaffolds
title_fullStr Manufacturing and assessment of osteogenically enhanced hydroxyapatite/ calcium carbonate bone scaffolds
title_full_unstemmed Manufacturing and assessment of osteogenically enhanced hydroxyapatite/ calcium carbonate bone scaffolds
title_sort Manufacturing and assessment of osteogenically enhanced hydroxyapatite/ calcium carbonate bone scaffolds
author_id_str_mv 0b8e2c94c5ea2b8bc99f5cdaea16883f
author_id_fullname_str_mv 0b8e2c94c5ea2b8bc99f5cdaea16883f_***_EMMA STEIJVERS
author EMMA STEIJVERS
author2 EMMA STEIJVERS
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publishDate 2023
institution Swansea University
college_str Faculty of Medicine, Health and Life Sciences
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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 - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
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description Bone grafts are essential for repairing large bone defects, but natural sources are scarce and alternatives are needed. Hydroxyapatite/calcium carbonate scaffolds are osteocompatible and resorbable and thus suitable for bone grafts, but lack the growth factors and related osteogenicity present in natural grafts. This study aimed to enhance the osteogenic capacity of these bone scaffolds through two methods: 1) culturing and osteogenically differentiating mesenchymal stem cells onto the scaffolds in vitro so that they generate and deposit growth factors, and adding retinoic acid to increase cell differentiation and bone morphogenic protein expression, and 2) adding bisphosphonates, anti-osteoporotic medication, to the scaffolds to inhibit bone resorption and maximize the initial bone growth. Cell growth on scaffolds in vitro was analysed using fluorescence and scanning electron microscopy and metabolic assays, and growth factors were quantified using ELISA. The results indicate that MSCs grow and deposit BMPs onto the scaffolds. Osteogenic differentiation increased the amount after 14, but not 7 or 21 days of culture, while the addition of RA is detrimental to growth factor production. The effect of bisphosphonates was determined by implanting scaffolds treated with OX-14 and Zoledronate in vivo in mice, then quantifying the bone growth through μCT scanning and the gene expression using qPCR. The addition of Zoledronate, but not OX-14, increased the bone callus size at all time points. In conclusion, both approaches are promising methods to improve bone scaffold osteogenicity. Culturing cells onto scaffolds can be done to add growth factors to them, though future research should aim to increase the amount deposited. The addition of Zoledronate increases bone callus size, and future research should determine the effectiveness of this approach in critical-sized bone defects.
published_date 2023-09-27T14:59:30Z
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