VEGF-Loaded Heparinised Gelatine-Hydroxyapatite-Tricalcium Phosphate Scaffold Accelerates Bone Regeneration via Enhancing Osteogenesis-Angiogenesis Coupling
Background: Bone tissue defect, one of the common orthopaedicdiseases, is traumatizing and affects patient’s lifestyle. Although autologous and xenograft bone transplantations are performed in bone tissue engineering, clinical development of bone transplantation is limited because ofvarious factors,...
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Frontiers Media S.A.
2022-06-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2022.915181/full |
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author | Xu Chen Xu Chen Chun-Yan Gao Xiao-Yang Chu Chun-Yan Zheng Ying-Yi Luan Xin He Kai Yang Dong-Liang Zhang |
author_facet | Xu Chen Xu Chen Chun-Yan Gao Xiao-Yang Chu Chun-Yan Zheng Ying-Yi Luan Xin He Kai Yang Dong-Liang Zhang |
author_sort | Xu Chen |
collection | DOAJ |
description | Background: Bone tissue defect, one of the common orthopaedicdiseases, is traumatizing and affects patient’s lifestyle. Although autologous and xenograft bone transplantations are performed in bone tissue engineering, clinical development of bone transplantation is limited because ofvarious factors, such as varying degrees of immune rejection, lack of bone sources, and secondary damage to bone harvesting.Methods: We synthesised a heparinised gelatine-hydroxyapatite-tricalcium phosphate (HG-HA-TCP) scaffold loaded with sustained-release vascular endothelial growth factor (VEGF) analysed their structure, mechanical properties, and biocompatibility. Additionally, the effects of HG-HA-TCP (VEGF) scaffolds on osteogenic differentiation and vascularisation of stem cells from human exfoliated deciduous teeth (SHED) in vitro and bone regeneration in vivo were investigated.Results: HG-HA-TCP scaffold possessed good pore structure, mechanical properties, and biocompatibility. HG-HA-TCP scaffold loaded with VEGF could effectively promote SHED proliferation, migration, and adhesion. Moreover, HG-HA-TCP (VEGF) scaffold increased the expression of osteogenesis- and angiogenesis-related genes and promoted osteogenic differentiation and vascularisation in cells. In vivo results demonstrated that VEGF-loaded HG-HA-TCP scaffold improved new bone regeneration and enhanced bone mineral density, revealed byhistological, micro-CT and histochemical straining analyses. Osteogenic and angiogenic abilities of the three biological scaffolds wereranked as follows: HG-HA-TCP (VEGF) > G-HA-TCP (VEGF) > G-HA-TCP.Conclusion: HG-HA-TCP (VEGF) scaffold with good biocompatibility could create an encouraging osteogenic microenvironment that could accelerate vessel formation and osteogenesis, providing an effective scaffold for bone tissue engineering and developing new clinical treatment strategies for bone tissue defects. |
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spelling | doaj.art-3bd2cc102eaa49869ced9ffd8583facb2022-12-22T02:29:06ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-06-011010.3389/fbioe.2022.915181915181VEGF-Loaded Heparinised Gelatine-Hydroxyapatite-Tricalcium Phosphate Scaffold Accelerates Bone Regeneration via Enhancing Osteogenesis-Angiogenesis CouplingXu Chen0Xu Chen1Chun-Yan Gao2Xiao-Yang Chu3Chun-Yan Zheng4Ying-Yi Luan5Xin He6Kai Yang7Dong-Liang Zhang8Department of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, Beijing, ChinaDepartment of Stomatology, Eighth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, Beijing, ChinaDepartment of Stomatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, Beijing, ChinaPrenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, ChinaDepartment of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, Beijing, ChinaPrenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, ChinaDepartment of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, Beijing, ChinaBackground: Bone tissue defect, one of the common orthopaedicdiseases, is traumatizing and affects patient’s lifestyle. Although autologous and xenograft bone transplantations are performed in bone tissue engineering, clinical development of bone transplantation is limited because ofvarious factors, such as varying degrees of immune rejection, lack of bone sources, and secondary damage to bone harvesting.Methods: We synthesised a heparinised gelatine-hydroxyapatite-tricalcium phosphate (HG-HA-TCP) scaffold loaded with sustained-release vascular endothelial growth factor (VEGF) analysed their structure, mechanical properties, and biocompatibility. Additionally, the effects of HG-HA-TCP (VEGF) scaffolds on osteogenic differentiation and vascularisation of stem cells from human exfoliated deciduous teeth (SHED) in vitro and bone regeneration in vivo were investigated.Results: HG-HA-TCP scaffold possessed good pore structure, mechanical properties, and biocompatibility. HG-HA-TCP scaffold loaded with VEGF could effectively promote SHED proliferation, migration, and adhesion. Moreover, HG-HA-TCP (VEGF) scaffold increased the expression of osteogenesis- and angiogenesis-related genes and promoted osteogenic differentiation and vascularisation in cells. In vivo results demonstrated that VEGF-loaded HG-HA-TCP scaffold improved new bone regeneration and enhanced bone mineral density, revealed byhistological, micro-CT and histochemical straining analyses. Osteogenic and angiogenic abilities of the three biological scaffolds wereranked as follows: HG-HA-TCP (VEGF) > G-HA-TCP (VEGF) > G-HA-TCP.Conclusion: HG-HA-TCP (VEGF) scaffold with good biocompatibility could create an encouraging osteogenic microenvironment that could accelerate vessel formation and osteogenesis, providing an effective scaffold for bone tissue engineering and developing new clinical treatment strategies for bone tissue defects.https://www.frontiersin.org/articles/10.3389/fbioe.2022.915181/fullheparinVEGFgelatinehydroxyapatitetricalcium phosphatebone regeneration |
spellingShingle | Xu Chen Xu Chen Chun-Yan Gao Xiao-Yang Chu Chun-Yan Zheng Ying-Yi Luan Xin He Kai Yang Dong-Liang Zhang VEGF-Loaded Heparinised Gelatine-Hydroxyapatite-Tricalcium Phosphate Scaffold Accelerates Bone Regeneration via Enhancing Osteogenesis-Angiogenesis Coupling Frontiers in Bioengineering and Biotechnology heparin VEGF gelatine hydroxyapatite tricalcium phosphate bone regeneration |
title | VEGF-Loaded Heparinised Gelatine-Hydroxyapatite-Tricalcium Phosphate Scaffold Accelerates Bone Regeneration via Enhancing Osteogenesis-Angiogenesis Coupling |
title_full | VEGF-Loaded Heparinised Gelatine-Hydroxyapatite-Tricalcium Phosphate Scaffold Accelerates Bone Regeneration via Enhancing Osteogenesis-Angiogenesis Coupling |
title_fullStr | VEGF-Loaded Heparinised Gelatine-Hydroxyapatite-Tricalcium Phosphate Scaffold Accelerates Bone Regeneration via Enhancing Osteogenesis-Angiogenesis Coupling |
title_full_unstemmed | VEGF-Loaded Heparinised Gelatine-Hydroxyapatite-Tricalcium Phosphate Scaffold Accelerates Bone Regeneration via Enhancing Osteogenesis-Angiogenesis Coupling |
title_short | VEGF-Loaded Heparinised Gelatine-Hydroxyapatite-Tricalcium Phosphate Scaffold Accelerates Bone Regeneration via Enhancing Osteogenesis-Angiogenesis Coupling |
title_sort | vegf loaded heparinised gelatine hydroxyapatite tricalcium phosphate scaffold accelerates bone regeneration via enhancing osteogenesis angiogenesis coupling |
topic | heparin VEGF gelatine hydroxyapatite tricalcium phosphate bone regeneration |
url | https://www.frontiersin.org/articles/10.3389/fbioe.2022.915181/full |
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