Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi'an, PR China.
Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an, PR China.
Arch Med Sci. 2014 Feb 24;10(1):174-81. doi: 10.5114/aoms.2012.30950. Epub 2012 Oct 8.
Large osseous defect remains a serious clinical problem due to the lack of sufficient blood supply and it has been proposed that this situation can be relieved by accelerating the formation of new vessels in the process of bone defect repair. The aim of this study was to develop a new type of artificial bone by transferring the VEGF gene into marrow stromal cells (MSCs) and seeding them into a porous scaffold.
An adenovirus vector was employed to transfer the VEGF gene into MSCs and expression of the exogenous gene was confirmed by ELISA. Next the transduced cells were seeded into a collagen I modified PLGA/TCP scaffold. The constructed new complex artificial bone was then assessed for biocompatibility in vitro and blood vessel formation and bone formation in vivo.
We found that adenovirus mediated VEGF gene transfer into MSCs sustained VEGF expression in MSCs for 3 weeks. Porous scaffold PLGA/TCP made by rapid prototyping technology exhibited improved biocompatibility resulting from crosslinking with collagen I. Furthermore, the in vivo study showed that large amounts of blood vessels were detected histologically 1 week after artificial bone implantation, and significant bone formation was detected 8 weeks after implantation.
Our findings suggest that gene transfer of VEGF into MSCs combined with PLGA/TCP scaffold enhances bone repair in vivo by promoting vascularization.
由于缺乏充足的血液供应,大的骨缺损仍然是一个严重的临床问题,有人提出,在骨缺损修复过程中加速新血管的形成可以缓解这种情况。本研究的目的是通过将 VEGF 基因转移到骨髓基质细胞(MSCs)中并将其接种到多孔支架上来开发一种新型人工骨。
采用腺病毒载体将 VEGF 基因转染到 MSCs 中,并通过 ELISA 证实外源性基因的表达。然后将转染的细胞接种到胶原 I 修饰的 PLGA/TCP 支架上。然后评估构建的新型复合人工骨的体外生物相容性以及体内血管形成和骨形成。
我们发现腺病毒介导的 VEGF 基因转染到 MSCs 中可使 MSCs 中的 VEGF 表达持续 3 周。通过与胶原 I 交联,由快速成型技术制成的多孔支架 PLGA/TCP 显示出改善的生物相容性。此外,体内研究表明,在人工骨植入后 1 周即可通过组织学检测到大量血管,植入后 8 周即可检测到明显的骨形成。
我们的研究结果表明,将 VEGF 基因转染到 MSCs 中并结合 PLGA/TCP 支架可通过促进血管生成来增强体内骨修复。