聚乙烯亚胺在骨组织工程中的研究进展和应用前景

Research progress and application prospect of polyethyleneimine in bone tissue engineering

背景:聚乙烯亚胺作为一种阳离子聚合物,目前在医学的诸多领域已得到广泛的研究,凭借自身丰富的胺基基团和阳离子电荷,使其具备易修饰性和静电吸附性,这些特性运用于骨组织工程中,具有潜在的优势与前景。目的:总结目前聚乙烯亚胺在骨组织工程的研究进展,并且对其用于骨组织工程中的应用前景作了讨论与展望。方法:检索2000年1月至2022年3月PubMed、Web of Science、中国知网及万方数据库中相关文献,英文检索词:“polyethyleneimine,bone tissue engineering,bone tissue regeneration,bone tissue repair,regenerative medicine,drug delivery”;中文检索词:“聚乙烯亚胺、骨组织工程、骨组织再生、骨组织修复、再生医学、药物递送”,最终纳入57篇文献进行综述分析。结果与结论:(1)基于基因技术利用聚乙烯亚胺与成骨相关基因形成的复合物是一种高效的基因载体,能够诱导种子细胞表达成骨相关的细胞因子,促进成骨分化;通过与不同基团进行修饰,可以实现在不影响聚乙烯亚胺转染效率的同时尽可能的降低对间充质干细胞等种子细胞的毒性,但是对于DNA和聚乙烯亚胺链的长度、聚乙烯亚胺的电荷密度、结构和化学修饰以及氮/磷酸盐等关键参数未达成共识。(2)聚乙烯亚胺作为表面涂层或直接与支架材料形成复合物制备的骨缺修复支架,在支架的生物相容性、降解速率、孔隙大小和机械强度方面均有优化;同时聚乙烯亚胺及其衍生物应用于骨缺损修复支架可以赋予支架抗菌性和增强促血管生成的能力。(3)体内加载成骨诱导因子方面,聚乙烯亚胺搭载的成骨诱导因子基因在体外细胞实验中具有高效的转染能力,负载在支架上植入骨缺损动物模型体内则能提升支架的生物相容性,具有理想的骨缺损修复效果,并且未有严重的不良反应报道,但是对于基因的异位插入及促成骨蛋白的异位表达仍然是目前存在的问题。(4)为实现药物骨靶向递送,聚乙烯亚胺凭借自身丰富的可修饰基团,成为了靶头与药物载体之间连接的“桥梁”。(5)基于双膦酸盐类、刺激响应性系统及生物素亲和素系统的药物靶向递送方式向骨修复支架靶向持续递送促成骨的药物目前尚未见报道,但聚乙烯亚胺目前在药物递送领域的应用提供了实现该想法的可能,未来值得进一步探索。

BACKGROUND:As a cationic polymer,polyethyleneimine has been widely studied in many fields of medicine.With its rich amino and cationic charges,it has the ability of easy modification and electrostatic adsorption,which has potential advantages and prospects for application in bone tissue enginee ring.OBJECTIVE:To summarize the research progress of polyethyleneimine in bone tissue engineering,and discuss and explore its development prospect in bone tissue engineering.METHODS:Relevant articles were searched on PubMed,Web of Science,CNKI,and Wanfang databases from January 2000 to March 2022 with the search terms of"polyethyleneimine,bone tissue enginee ring,bone tissue regeneration,bone tissue repair,regenerative medicine,drug delivery in English and Chinese.Finally,57 articles were included for analysis.RESULTS AND CONCLUSION:(1)The complex formed by polyethyleneimine and osteogenic genes based on gene technology is an efficient gene carrie r,which can induce seed cells to express osteogenic cytokines and promote osteogenic differentiation.Modification with different groups can reduce the toxicity to seed cells such as mesenchymal stem cells as much as possible without affecting the transfection efficiency of polyethyleneimine.However,no consensus was reached on the key parameters such as the length of DNA and polyethyleneimine chains,charge density of polyethyleneimine,structure and chemical modification,and nitrogen/phosphate.(2)Polyethyleneimine has been optimized in the aspects of biocompatibility,degradation rate,pore size and mechanical strength of the scaffold as a surfa ce coating or a composite prepared directly with the scaffold material.Meanwhile,the application of polyethyleneimine and its derivatives in bone defect repair scaffolds can give the antibacterial activity of scaffolds and enhance the ability of promoting angiogenesis.(3)In terms of in vivo loading of osteogenic inducible factor,the osteogenic inducible factor gene carried by polyethyleneimine had efficient transfection ability in vitro cell experiments.When loaded on the scaffold and implanted into the bone defect animal model,the biocompatibility of the scaffold could be improved,and the bone defect repair effect was ideal,and no serious adverse reactions were reported.However,ectopic gene insertion and promoting ectopic expression of bone protein are still existing pro blems.(4)In order to achieve targeted drug bone delivery,polyethyleneimine is a"bridge"between target and drug carrier with its abundant modifiable groups.(5)The targeted drug delive ry method based on bisphosphonates,stimulus response system and biotin avidin system has not been reported yet,but the current application of polyethyleneimine in the field of drug delivery provides the possibility of realizing this idea,which is wo rth further exploration.