Rapid assessment of the osteogenic capacity of hydroxyapatite/aragonite using a murine tibial periosteal ossification model

Biomaterials are widely used as orthopaedic implants and bone graft substitutes. We aimed to develop a rapid osteogenic assessment method using a murine tibial periosteal ossification model to evaluate the bone formation/remodelling potential of a biomaterial within 2–4 weeks. A novel hydroxyapatite...

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Main Authors: Emma Steijvers, Yunshong Shi, Hong Lu, Weixin Zhang, Yitian Zhang, Feihu Zhao, Baichuan Wang, Louise Hughes, Jake E. Barralet, Giulia Degli-Alessandrini, Igor Kraev, Richard Johnston, Zengwu Shao, Frank H. Ebetino, James T. Triffitt, R. Graham G. Russell, Davide Deganello, Xu Cao, Zhidao Xia
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-03-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X24005097
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author Emma Steijvers
Yunshong Shi
Hong Lu
Weixin Zhang
Yitian Zhang
Feihu Zhao
Baichuan Wang
Louise Hughes
Jake E. Barralet
Giulia Degli-Alessandrini
Igor Kraev
Richard Johnston
Zengwu Shao
Frank H. Ebetino
James T. Triffitt
R. Graham G. Russell
Davide Deganello
Xu Cao
Zhidao Xia
author_facet Emma Steijvers
Yunshong Shi
Hong Lu
Weixin Zhang
Yitian Zhang
Feihu Zhao
Baichuan Wang
Louise Hughes
Jake E. Barralet
Giulia Degli-Alessandrini
Igor Kraev
Richard Johnston
Zengwu Shao
Frank H. Ebetino
James T. Triffitt
R. Graham G. Russell
Davide Deganello
Xu Cao
Zhidao Xia
author_sort Emma Steijvers
collection DOAJ
description Biomaterials are widely used as orthopaedic implants and bone graft substitutes. We aimed to develop a rapid osteogenic assessment method using a murine tibial periosteal ossification model to evaluate the bone formation/remodelling potential of a biomaterial within 2–4 weeks. A novel hydroxyapatite/aragonite (HAA) biomaterial was implanted into C57BL/6 mice juxtaskeletally between the tibia and tibialis anterior muscle. Rapid intramembranous bone formation was observed at 14 days, with 4- to 8-fold increases in bone thickness and callus volume in comparison with sham-operated animals (p < 0.0001), followed by bone remodelling and a new layer of cortical bone formation by 28 days after implantation. The addition of zoledronate, a clinically-utilised bisphosphonate, to HAA, promoted significantly more new bone formation than HAA alone over 28 days (p < 0.01). The osteogenic potential of HAA was further confirmed by implanting into a 3.5 mm diameter femoral cancellous bone defect in rats and a 5 mm diameter femoral cortical bone defect in minipigs. To understand the biodegradation and the cellular activity at the cell/biomaterial interfaces, non-decalcified specimens were resin embedded and sections subjected to combined scanning electron microscopy (SEM)/electron backscatter diffraction (EBSD)/energy dispersive X-ray spectrometry (EDS) analysis. We conclude that murine tibial periosteal ossification is a novel method for rapid assessment of the interaction of bioactive materials with osteogenic tissues. This study also highlights that combining calcium carbonate with hydroxyapatite enhances biodegradation and osteogenesis.
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spelling doaj-art-6625a9c896de4e58b4195cad2602b0ee2025-01-26T05:04:24ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-03-0145257273Rapid assessment of the osteogenic capacity of hydroxyapatite/aragonite using a murine tibial periosteal ossification modelEmma Steijvers0Yunshong Shi1Hong Lu2Weixin Zhang3Yitian Zhang4Feihu Zhao5Baichuan Wang6Louise Hughes7Jake E. Barralet8Giulia Degli-Alessandrini9Igor Kraev10Richard Johnston11Zengwu Shao12Frank H. Ebetino13James T. Triffitt14R. Graham G. Russell15Davide Deganello16Xu Cao17Zhidao Xia18Centre for Nanohealth, Swansea University Medical School, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, United KingdomCentre for Nanohealth, Swansea University Medical School, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, United Kingdom; School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaCentre for Nanohealth, Swansea University Medical School, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, United Kingdom; Department of Orthopaedics, Xiangyang Central Hospital, No. 136, Jingzhou Street, Xiangyang City, Hubei Province, ChinaDepartment of Orthopaedics, Johns Hopkins Medical School, Baltimore, MD, 21205, United StatesFaculty of Science and Engineering, Swansea University, Swansea, United KingdomFaculty of Science and Engineering, Swansea University, Swansea, United KingdomCentre for Nanohealth, Swansea University Medical School, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, United Kingdom; Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaOxford Instruments NanoAnalysis, Halifax Road, High Wycombe, Bucks, HP12 3SE, United KingdomFaculty of Dentistry and Health Sciences, Surgical and Interventional Sciences Division, Department of Surgery, Faculty of Medicine and Health Sciences, McGill University, Quebec, CanadaThe Open University, Electron Microscopy Suite, Walton Hall, Milton Keynes, MK7 6AA, United KingdomThe Open University, Electron Microscopy Suite, Walton Hall, Milton Keynes, MK7 6AA, United KingdomFaculty of Science and Engineering, Swansea University, Swansea, United KingdomDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Chemistry, University of Rochester, Rochester, NY, 14627, United StatesNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, Oxford, United KingdomNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, Oxford, United Kingdom; The Mellanby Centre for Musculoskeletal Research, Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield Medical School, Sheffield, S10 2RX, United KingdomFaculty of Science and Engineering, Swansea University, Swansea, United KingdomDepartment of Orthopaedics, Johns Hopkins Medical School, Baltimore, MD, 21205, United States; Corresponding author. Department of Orthopaedics, Johns Hopkins Medical School, Baltimore, MD, 21205, United States.Centre for Nanohealth, Swansea University Medical School, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, United Kingdom; Corresponding author. Centre for Nanohealth, Swansea University Medical School, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, SA2 8PP, United Kingdom.Biomaterials are widely used as orthopaedic implants and bone graft substitutes. We aimed to develop a rapid osteogenic assessment method using a murine tibial periosteal ossification model to evaluate the bone formation/remodelling potential of a biomaterial within 2–4 weeks. A novel hydroxyapatite/aragonite (HAA) biomaterial was implanted into C57BL/6 mice juxtaskeletally between the tibia and tibialis anterior muscle. Rapid intramembranous bone formation was observed at 14 days, with 4- to 8-fold increases in bone thickness and callus volume in comparison with sham-operated animals (p < 0.0001), followed by bone remodelling and a new layer of cortical bone formation by 28 days after implantation. The addition of zoledronate, a clinically-utilised bisphosphonate, to HAA, promoted significantly more new bone formation than HAA alone over 28 days (p < 0.01). The osteogenic potential of HAA was further confirmed by implanting into a 3.5 mm diameter femoral cancellous bone defect in rats and a 5 mm diameter femoral cortical bone defect in minipigs. To understand the biodegradation and the cellular activity at the cell/biomaterial interfaces, non-decalcified specimens were resin embedded and sections subjected to combined scanning electron microscopy (SEM)/electron backscatter diffraction (EBSD)/energy dispersive X-ray spectrometry (EDS) analysis. We conclude that murine tibial periosteal ossification is a novel method for rapid assessment of the interaction of bioactive materials with osteogenic tissues. This study also highlights that combining calcium carbonate with hydroxyapatite enhances biodegradation and osteogenesis.http://www.sciencedirect.com/science/article/pii/S2452199X24005097Osteogenesis assessmentIntramembranous ossificationTibial periosteal bone formationHydroxyapatite/aragoniteBiomaterials
spellingShingle Emma Steijvers
Yunshong Shi
Hong Lu
Weixin Zhang
Yitian Zhang
Feihu Zhao
Baichuan Wang
Louise Hughes
Jake E. Barralet
Giulia Degli-Alessandrini
Igor Kraev
Richard Johnston
Zengwu Shao
Frank H. Ebetino
James T. Triffitt
R. Graham G. Russell
Davide Deganello
Xu Cao
Zhidao Xia
Rapid assessment of the osteogenic capacity of hydroxyapatite/aragonite using a murine tibial periosteal ossification model
Bioactive Materials
Osteogenesis assessment
Intramembranous ossification
Tibial periosteal bone formation
Hydroxyapatite/aragonite
Biomaterials
title Rapid assessment of the osteogenic capacity of hydroxyapatite/aragonite using a murine tibial periosteal ossification model
title_full Rapid assessment of the osteogenic capacity of hydroxyapatite/aragonite using a murine tibial periosteal ossification model
title_fullStr Rapid assessment of the osteogenic capacity of hydroxyapatite/aragonite using a murine tibial periosteal ossification model
title_full_unstemmed Rapid assessment of the osteogenic capacity of hydroxyapatite/aragonite using a murine tibial periosteal ossification model
title_short Rapid assessment of the osteogenic capacity of hydroxyapatite/aragonite using a murine tibial periosteal ossification model
title_sort rapid assessment of the osteogenic capacity of hydroxyapatite aragonite using a murine tibial periosteal ossification model
topic Osteogenesis assessment
Intramembranous ossification
Tibial periosteal bone formation
Hydroxyapatite/aragonite
Biomaterials
url http://www.sciencedirect.com/science/article/pii/S2452199X24005097
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