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,...

Full description

Bibliographic Details
Main Authors: Xu Chen, Chun-Yan Gao, Xiao-Yang Chu, Chun-Yan Zheng, Ying-Yi Luan, Xin He, Kai Yang, Dong-Liang Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2022.915181/full
_version_ 1828334377374842880
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.
first_indexed 2024-04-13T21:32:15Z
format Article
id doaj.art-3bd2cc102eaa49869ced9ffd8583facb
institution Directory Open Access Journal
issn 2296-4185
language English
last_indexed 2024-04-13T21:32:15Z
publishDate 2022-06-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Bioengineering and Biotechnology
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
work_keys_str_mv AT xuchen vegfloadedheparinisedgelatinehydroxyapatitetricalciumphosphatescaffoldacceleratesboneregenerationviaenhancingosteogenesisangiogenesiscoupling
AT xuchen vegfloadedheparinisedgelatinehydroxyapatitetricalciumphosphatescaffoldacceleratesboneregenerationviaenhancingosteogenesisangiogenesiscoupling
AT chunyangao vegfloadedheparinisedgelatinehydroxyapatitetricalciumphosphatescaffoldacceleratesboneregenerationviaenhancingosteogenesisangiogenesiscoupling
AT xiaoyangchu vegfloadedheparinisedgelatinehydroxyapatitetricalciumphosphatescaffoldacceleratesboneregenerationviaenhancingosteogenesisangiogenesiscoupling
AT chunyanzheng vegfloadedheparinisedgelatinehydroxyapatitetricalciumphosphatescaffoldacceleratesboneregenerationviaenhancingosteogenesisangiogenesiscoupling
AT yingyiluan vegfloadedheparinisedgelatinehydroxyapatitetricalciumphosphatescaffoldacceleratesboneregenerationviaenhancingosteogenesisangiogenesiscoupling
AT xinhe vegfloadedheparinisedgelatinehydroxyapatitetricalciumphosphatescaffoldacceleratesboneregenerationviaenhancingosteogenesisangiogenesiscoupling
AT kaiyang vegfloadedheparinisedgelatinehydroxyapatitetricalciumphosphatescaffoldacceleratesboneregenerationviaenhancingosteogenesisangiogenesiscoupling
AT dongliangzhang vegfloadedheparinisedgelatinehydroxyapatitetricalciumphosphatescaffoldacceleratesboneregenerationviaenhancingosteogenesisangiogenesiscoupling