负载血管内皮生长因子的肝素化明胶-羟基磷灰石-磷酸三钙支架通过增强成骨-血管生成耦合加速骨再生。
VEGF-Loaded Heparinised Gelatine-Hydroxyapatite-Tricalcium Phosphate Scaffold Accelerates Bone Regeneration Enhancing Osteogenesis-Angiogenesis Coupling.
作者信息
Chen Xu, Gao Chun-Yan, Chu Xiao-Yang, Zheng Chun-Yan, Luan Ying-Yi, He Xin, Yang Kai, Zhang Dong-Liang
机构信息
Department of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, Beijing, China.
Department of Stomatology, Eighth Medical Center of Chinese PLA General Hospital, Beijing, China.
出版信息
Front Bioeng Biotechnol. 2022 Jun 8;10:915181. doi: 10.3389/fbioe.2022.915181. eCollection 2022.
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. 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) and bone regeneration were investigated. 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. 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. 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.
骨组织缺损是常见的骨科疾病之一,具有创伤性,会影响患者的生活方式。尽管在骨组织工程中进行了自体和异种骨移植,但由于各种因素,如不同程度的免疫排斥、骨源缺乏以及取骨的二次损伤等,骨移植的临床发展受到限制。我们合成了一种负载缓释血管内皮生长因子(VEGF)的肝素化明胶 - 羟基磷灰石 - 磷酸三钙(HG - HA - TCP)支架,分析了其结构、力学性能和生物相容性。此外,还研究了HG - HA - TCP(VEGF)支架对人乳牙脱落干细胞(SHED)的成骨分化、血管生成及骨再生的影响。HG - HA - TCP支架具有良好的孔隙结构、力学性能和生物相容性。负载VEGF的HG - HA - TCP支架能有效促进SHED的增殖、迁移和黏附。此外,HG - HA - TCP(VEGF)支架增加了成骨和血管生成相关基因的表达,促进了细胞的成骨分化和血管生成。组织学、显微CT和组织化学染色分析结果表明,负载VEGF的HG - HA - TCP支架改善了新骨再生并提高了骨密度。三种生物支架的成骨和血管生成能力排序如下:HG - HA - TCP(VEGF)> G - HA - TCP(VEGF)> G - HA - TCP。具有良好生物相容性的HG - HA - TCP(VEGF)支架可以创建一个促进成骨的微环境,加速血管形成和成骨过程,为骨组织工程提供有效的支架,并为骨组织缺损开发新的临床治疗策略。