生物电效应材料在骨组织工程支架设计中的应用

Application of bioelectric effect materials in design of bone tissue engineering scaffolds

背景:骨具有生物电效应,然而骨缺损的发生会导致骨骼内源性生物电的缺失。具有生物电效应的骨组织工程支架植入骨缺损处会补足缺失的电信号,加速骨缺损的修复。目的:文章介绍了骨组织的生物电效应,阐述了电刺激对骨缺损的修复作用,总结了生物电效应应用于骨组织工程的研究进展,以期为骨组织工程的研究提供新的思路。方法:以“bioelectrical effect,bioelectrical materials,electrical stimulation,bone tissue engineering,bone scaffold,bone defect,bone repair,osteogenesis”为英文检索词,以“生物电效应,生物电支架,电刺激,骨组织工程,骨支架,骨缺损,骨修复,骨再生”为中文检索词,在中国知网、万方、PubMed、Web of Science和ScienceDirect数据库检索与生物电效应骨组织工程支架相关的文献,最终纳入87篇进行系统归纳、总结和分析。结果与结论:①生物电效应结合体外电刺激设计骨组织工程支架是一种理想可行的方法,主要涉及的材料包括金属材料、石墨烯材料、天然生物衍生材料以及人工合成生物材料;目前运用最广泛的导电材料是石墨烯材料,得益于自身的超强导电性能、大比表面积、同细胞及骨骼的良好生物相容性以及优异的力学性能。②石墨烯材料主要是作为修饰材料引入支架以增强整体支架的电导率,同时其大表面积和丰富的官能团能够促进生物活性物质的装载和释放。③然而生物电效应的骨组织工程支架尚存一些重大挑战需要克服:满足导电性能的同时还需考虑支架的综合性能;缺乏统一、标准化的生物电效应骨组织工程支架的制备方式;体外电刺激干预系统尚不够成熟;缺乏个体化指导支架的选择以实现针对不同病理情况的患者选择并设计最适宜的支架。④研究者们在设计导电支架时,要深入考虑支架的综合效应,譬如生物相容性、力学性能以及生物降解性能等,而此种综合性能可以通过多种材料的复合来实现。⑤除此之外,临床转化应该是导电支架设计的最终考量,在评估出电刺激作用于人体且有利于骨缺损修复的安全电流阈值的基础之上,设计动物实验以及基础实验,然后应用于临床,从而在未来实现生物电效应骨组织工程支架应用于临床的终极目标。

BACKGROUND:Bone has bioelectric effects.However,bone defects can lead to loss of endogenous bioelectricity in bone.The implantation of bone tissue engineering scaffolds with bioelectric effect into bone defects will replenish the missing electrical signals and accelerate the repair of bone defects.OBJECTIVE:To introduce the bioelectric effect of bone tissue and expound the repair effect of electrical stimulation on bone defects,summarize the research progress of bioelectric effect applied to bone tissue engineering,in order to provide new ideas for the research of bone tissue engineering.METHODS:Relevant articles were searched on CNKI,WanFang,PubMed,Web of Science and ScienceDirect databases,using“bioelectrical effect,bioelectrical materials,electrical stimulation,bone tissue engineering,bone scaffold,bone defect,bone repair,osteogenesis”as the English and Chinese search terms.Finally,87 articles were included for analysis.RESULTS AND CONCLUSION:(1)Bioelectrical effect combined with ex vivo electrical stimulation to design bone tissue engineering scaffolds is an ideal and feasible approach,and the main materials involved include metallic materials,graphene materials,natural bio-derived materials,and synthetic biomaterial.At present,the most widely used conductive material is graphene material,which benefits from its super conductivity,large specific surface area,good biocompatibility with cells and bones,and excellent mechanical properties.(2)Graphene materials are mainly introduced into the scaffold as modified materials to enhance the conductivity of the overall scaffold,while its large surface area and rich functional groups can promote the loading and release of bioactive substances.(3)However,there are still some major challenges to overcome for bioelectrically effective bone tissue engineering scaffolds:not only electrical conductivity but also the overall performance of the bracket needs to be considered;lack of uniform,standardized preparation of bioelectrically effective bone tissue engineering scaffolds;extracorporeal electrical stimulation intervention systems are not yet mature enough;lack of individualized guidance on stent selection to enable the selection and design of the most appropriate stent for patients with different pathologies.(4)When designing conductive scaffolds,researchers have to deeply consider the comprehensive effects of the scaffolds,such as biocompatibility,mechanical properties,and biodegradability.This combination of properties can be achieved by combining multiple materials.(5)Beyond that,clinical translation should be the ultimate consideration for conductive stent design.On the basis of evaluating the safe current threshold for electrical stimulation to act on the human body and facilitate the repair of bone defects,animal experiments as well as basic experiments are designed and then applied to the clinic to achieve the ultimate goal of applying bioelectrical effect bone tissue engineering scaffolds in the clinic.