Considerations of growth factor and material use in bone tissue engineering using biodegradable scaffolds in vitro and in vivo

Abstract Bone tissue engineering aims to harness materials to develop functional bone tissue to heal ‘critical-sized’ bone defects. This study examined a robust, coated poly(caprolactone) trimethacrylate (PCL-TMA) 3D-printable scaffold designed to augment bone formation. Following optimisation of th...

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Main Authors: Karen M. Marshall, Jonathan P. Wojciechowski, Vineetha Jayawarna, Abshar Hasan, Cécile Echalier, Øystein Øvrebø, Tao Yang, Kun Zhou, Janos M. Kanczler, Alvaro Mata, Manuel Salmeron-Sanchez, Molly M. Stevens, Richard O. C. Oreffo
Format: Article
Language:English
Published: Nature Portfolio 2024-10-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-75198-3
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author Karen M. Marshall
Jonathan P. Wojciechowski
Vineetha Jayawarna
Abshar Hasan
Cécile Echalier
Øystein Øvrebø
Tao Yang
Kun Zhou
Janos M. Kanczler
Alvaro Mata
Manuel Salmeron-Sanchez
Molly M. Stevens
Richard O. C. Oreffo
author_facet Karen M. Marshall
Jonathan P. Wojciechowski
Vineetha Jayawarna
Abshar Hasan
Cécile Echalier
Øystein Øvrebø
Tao Yang
Kun Zhou
Janos M. Kanczler
Alvaro Mata
Manuel Salmeron-Sanchez
Molly M. Stevens
Richard O. C. Oreffo
author_sort Karen M. Marshall
collection DOAJ
description Abstract Bone tissue engineering aims to harness materials to develop functional bone tissue to heal ‘critical-sized’ bone defects. This study examined a robust, coated poly(caprolactone) trimethacrylate (PCL-TMA) 3D-printable scaffold designed to augment bone formation. Following optimisation of the coatings, three bioactive coatings were examined, i) elastin-like polypeptide (ELP), ii) poly(ethyl acrylate) (PEA), fibronectin (FN) and bone morphogenetic protein-2 (BMP-2) applied sequentially (PEA/FN/BMP-2) and iii) both ELP and PEA/FN/BMP-2 coatings applied concurrently. The scaffold material was robust and showed biodegradability. The coatings demonstrated a significant (p < 0.05) osteogenic response in vitro in alkaline phosphatase gene upregulation and alkaline phosphatase production. The PCL-TMA scaffold and coatings supported angiogenesis and displayed excellent biocompatibility following evaluation on the chorioallantoic membrane assay. No significant (p < 0.05) heterotopic bone formed on the scaffolds within a murine subcutaneous implantation model, compared to the positive control of BMP-2 loaded collagen sponge following examination by micro-computed tomography or histology. The current studies demonstrate a range of innovative coated scaffold constructs with in vitro efficacy and clearly illustrate the importance of an appropriate in vivo environment to validate in vitro functionality prior to scale up and preclinical application.
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spelling doaj-art-0d419b7d66ce40a3b41f8cab151ffb492025-08-20T02:18:28ZengNature PortfolioScientific Reports2045-23222024-10-0114111810.1038/s41598-024-75198-3Considerations of growth factor and material use in bone tissue engineering using biodegradable scaffolds in vitro and in vivoKaren M. Marshall0Jonathan P. Wojciechowski1Vineetha Jayawarna2Abshar Hasan3Cécile Echalier4Øystein Øvrebø5Tao Yang6Kun Zhou7Janos M. Kanczler8Alvaro Mata9Manuel Salmeron-Sanchez10Molly M. Stevens11Richard O. C. Oreffo12Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of SouthamptonDepartment of Materials, Department of Bioengineering and Institute for Biomedical Engineering, Imperial College LondonSchool of Engineering, Centre for the Cellular Microenvironment, Advanced Research Centre, University of GlasgowSchool of Pharmacy, University of NottinghamDepartment of Materials, Department of Bioengineering and Institute for Biomedical Engineering, Imperial College LondonDepartment of Materials, Department of Bioengineering and Institute for Biomedical Engineering, Imperial College LondonDepartment of Materials, Department of Bioengineering and Institute for Biomedical Engineering, Imperial College LondonDepartment of Materials, Department of Bioengineering and Institute for Biomedical Engineering, Imperial College LondonBone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of SouthamptonSchool of Pharmacy, University of NottinghamSchool of Engineering, Centre for the Cellular Microenvironment, Advanced Research Centre, University of GlasgowDepartment of Materials, Department of Bioengineering and Institute for Biomedical Engineering, Imperial College LondonBone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of SouthamptonAbstract Bone tissue engineering aims to harness materials to develop functional bone tissue to heal ‘critical-sized’ bone defects. This study examined a robust, coated poly(caprolactone) trimethacrylate (PCL-TMA) 3D-printable scaffold designed to augment bone formation. Following optimisation of the coatings, three bioactive coatings were examined, i) elastin-like polypeptide (ELP), ii) poly(ethyl acrylate) (PEA), fibronectin (FN) and bone morphogenetic protein-2 (BMP-2) applied sequentially (PEA/FN/BMP-2) and iii) both ELP and PEA/FN/BMP-2 coatings applied concurrently. The scaffold material was robust and showed biodegradability. The coatings demonstrated a significant (p < 0.05) osteogenic response in vitro in alkaline phosphatase gene upregulation and alkaline phosphatase production. The PCL-TMA scaffold and coatings supported angiogenesis and displayed excellent biocompatibility following evaluation on the chorioallantoic membrane assay. No significant (p < 0.05) heterotopic bone formed on the scaffolds within a murine subcutaneous implantation model, compared to the positive control of BMP-2 loaded collagen sponge following examination by micro-computed tomography or histology. The current studies demonstrate a range of innovative coated scaffold constructs with in vitro efficacy and clearly illustrate the importance of an appropriate in vivo environment to validate in vitro functionality prior to scale up and preclinical application.https://doi.org/10.1038/s41598-024-75198-3Bioactive coatingBiomaterialBone tissue engineeringCAM assayAnimal models
spellingShingle Karen M. Marshall
Jonathan P. Wojciechowski
Vineetha Jayawarna
Abshar Hasan
Cécile Echalier
Øystein Øvrebø
Tao Yang
Kun Zhou
Janos M. Kanczler
Alvaro Mata
Manuel Salmeron-Sanchez
Molly M. Stevens
Richard O. C. Oreffo
Considerations of growth factor and material use in bone tissue engineering using biodegradable scaffolds in vitro and in vivo
Scientific Reports
Bioactive coating
Biomaterial
Bone tissue engineering
CAM assay
Animal models
title Considerations of growth factor and material use in bone tissue engineering using biodegradable scaffolds in vitro and in vivo
title_full Considerations of growth factor and material use in bone tissue engineering using biodegradable scaffolds in vitro and in vivo
title_fullStr Considerations of growth factor and material use in bone tissue engineering using biodegradable scaffolds in vitro and in vivo
title_full_unstemmed Considerations of growth factor and material use in bone tissue engineering using biodegradable scaffolds in vitro and in vivo
title_short Considerations of growth factor and material use in bone tissue engineering using biodegradable scaffolds in vitro and in vivo
title_sort considerations of growth factor and material use in bone tissue engineering using biodegradable scaffolds in vitro and in vivo
topic Bioactive coating
Biomaterial
Bone tissue engineering
CAM assay
Animal models
url https://doi.org/10.1038/s41598-024-75198-3
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