Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Molecules. 2013 May 15;18(5):5611-47. doi: 10.3390/molecules18055611.
Gene therapy involves the introduction of foreign genetic material into cells in order exert a therapeutic effect. The application of gene therapy to the field of orthopaedic tissue engineering is extremely promising as the controlled release of therapeutic proteins such as bone morphogenetic proteins have been shown to stimulate bone repair. However, there are a number of drawbacks associated with viral and synthetic non-viral gene delivery approaches. One natural polymer which has generated interest as a gene delivery vector is chitosan. Chitosan is biodegradable, biocompatible and non-toxic. Much of the appeal of chitosan is due to the presence of primary amine groups in its repeating units which become protonated in acidic conditions. This property makes it a promising candidate for non-viral gene delivery. Chitosan-based vectors have been shown to transfect a number of cell types including human embryonic kidney cells (HEK293) and human cervical cancer cells (HeLa). Aside from its use in gene delivery, chitosan possesses a range of properties that show promise in tissue engineering applications; it is biodegradable, biocompatible, has anti-bacterial activity, and, its cationic nature allows for electrostatic interaction with glycosaminoglycans and other proteoglycans. It can be used to make nano- and microparticles, sponges, gels, membranes and porous scaffolds. Chitosan has also been shown to enhance mineral deposition during osteogenic differentiation of MSCs in vitro. The purpose of this review is to critically discuss the use of chitosan as a gene delivery vector with emphasis on its application in orthopedic tissue engineering.
基因治疗涉及将外源遗传物质导入细胞，以发挥治疗作用。将基因治疗应用于骨科组织工程领域具有巨大的潜力，因为已证明控制释放治疗蛋白（如骨形态发生蛋白）可刺激骨修复。然而，病毒和合成非病毒基因传递方法存在许多缺点。一种已被用作基因传递载体的天然聚合物是壳聚糖。壳聚糖具有生物降解性、生物相容性和无毒性。壳聚糖之所以具有吸引力，主要是因为其重复单元中存在伯胺基团，在酸性条件下会质子化。这一特性使其成为非病毒基因传递的有前途的候选物。壳聚糖基载体已被证明可转染多种细胞类型，包括人胚肾细胞（HEK293）和人宫颈癌细胞（HeLa）。除了在基因传递中的应用外，壳聚糖还具有一系列在组织工程应用中显示出前景的特性；它具有生物降解性、生物相容性、具有抗菌活性，并且其阳离子性质允许与糖胺聚糖和其他蛋白聚糖发生静电相互作用。它可以用于制造纳米和微米颗粒、海绵、凝胶、膜和多孔支架。壳聚糖还被证明可以增强间充质干细胞在体外成骨分化过程中的矿物质沉积。本文的目的是批判性地讨论壳聚糖作为基因传递载体的应用，重点介绍其在骨科组织工程中的应用。
