Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
J Control Release. 2013 Sep 28;170(3):421-9. doi: 10.1016/j.jconrel.2013.06.013. Epub 2013 Jun 18.
Gene delivering biomaterials have increasingly been employed to modulate the cellular microenvironment to promote tissue regeneration, yet low transduction efficiency has been a persistent challenge for in vivo applications. In this report, we investigated the surface modification of poly(lactide-co-glycolide) (PLG) scaffolds with polysaccharides, which have been implicated in binding lentivirus but have not been used for delivery. Chitosan was directly conjugated onto PLG scaffolds, whereas heparin and hyaluronan were indirectly conjugated onto PLG scaffolds with multi-amine crosslinkers. The addition of chitosan and heparin onto PLG promoted the association of lentivirus to these scaffolds and enhanced their transduction efficiency in vitro relative to hyaluronan-conjugated and control scaffolds that had limited lentivirus association and transduction. Transduction efficiency in vitro was increased partly due to an enhanced retention of virus on the scaffold as well as an extended half-life of viral activity. Transduction efficiency was also evaluated in vivo using porous, multiple channel PLG bridges that delivered lentivirus to the injured mouse spinal cord. Transgene expression persisted for weeks after implantation, and was able to enhance axon growth and myelination. These studies support gene-delivering PLG scaffolds for in vivo regenerative medicine applications.
基因传递生物材料越来越多地被用于调节细胞微环境以促进组织再生，但转导效率低一直是体内应用的一个持续挑战。在本报告中，我们研究了多糖对聚（乳酸-共-乙醇酸）（PLG）支架的表面修饰，多糖与慢病毒结合有关，但尚未用于递送。壳聚糖直接接枝到 PLG 支架上，而肝素和透明质酸通过多胺交联剂间接接枝到 PLG 支架上。壳聚糖和肝素的添加促进了慢病毒与这些支架的结合，并提高了它们在体外的转导效率，与透明质酸接枝和对照支架相比，后者与慢病毒的结合和转导有限。体外转导效率的提高部分归因于病毒在支架上的保留增强以及病毒活性的半衰期延长。还使用多孔、多通道 PLG 桥在体内评估了转导效率，该桥将慢病毒递送至受伤的小鼠脊髓。植入后数周内持续表达转基因，并能够增强轴突生长和髓鞘形成。这些研究支持用于体内再生医学应用的基因传递 PLG 支架。
