3D printed microchannel networks to direct vascularisation during endochondral bone repair
3D printed microchannel networks to direct vascularisation during endochondral bone repair
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DOI：
10.1016/j.biomaterials.2018.01.057
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发表时间：
2018-04-01
期刊：
影响因子：
14
通讯作者：
Kelly, Daniel J.
中科院分区：
文献类型：
--
作者：
Daly, Andrew C.;Pitacco, Pierluca;Kelly, Daniel J.
骨组织工程策略概括了软骨内成骨的发育过程，为骨修复提供了一条有前途的途径。这种软骨内组织工程策略的临床转化将需要克服许多挑战，包括大型且解剖结构复杂的软骨移植物的工程设计，以及植入大型骨缺损后无血管软骨核心区域的持久性。在这里，3D打印技术被用来开发一种通用的、可扩展的方法来指导软骨内骨修复过程中的血管化。首先，使用牺牲pluronic墨水在装载明胶-甲基丙烯酰（GelMA）水凝胶的间充质干细胞（MSC）中3D打印相互连接的微通道网络。这些构建体（带微通道和不带微通道）随后在体外进行软骨诱导，然后植入大鼠临界大小的股骨缺损。与未处理的对照组相比，实体和微通道软骨模板增强了骨修复，实体软骨模板（没有微通道）支持最高水平的总骨形成。然而，3D打印的微通道被发现在植入后促进破骨细胞/免疫细胞入侵、水凝胶降解和血管化。此外，发现软骨内骨组织工程策略支持与BMP-2递送相当水平的骨愈合，同时促进较低水平的异位骨形成，微通道模板支持最低水平的异位骨形成。综上所述，这些结果表明，3D打印增生性软骨移植物代表了修复复杂骨折的一种有希望的方法，特别是对于血管化将是一个关键挑战的较大缺陷。(C) 2018 Elsevier Ltd.版权所有。
Bone tissue engineering strategies that recapitulate the developmental process of endochondral ossification offer a promising route to bone repair. Clinical translation of such endochondral tissue engineering strategies will require overcoming a number of challenges, including the engineering of large and often, anatomically complex cartilage grafts, as well as the persistence of core regions of avascular cartilage following their implantation into large bone defects. Here 3D printing technology is utilized to develop a versatile and scalable approach to guide vascularisation during endochondral bone repair. First, a sacrificial pluronic ink was used to 3D print interconnected microchannel networks in a mesenchymal stem cell (MSC) laden gelatin-methacryloyl (GelMA) hydrogel. These constructs (with and without microchannels) were next chondrogenically primed in vitro and then implanted into critically sized femoral bone defects in rats. The solid and microchanneled cartilage templates enhanced bone repair compared to untreated controls, with the solid cartilage templates (without microchannels) supporting the highest levels of total bone formation. However, the inclusion of 3D printed microchannels was found to promote osteoclast/immune cell invasion, hydrogel degradation, and vascularisation following implantation. In addition, the endochondral bone tissue engineering strategy was found to support comparable levels of bone healing to BMP-2 delivery, whilst promoting lower levels of heterotopic bone formation, with the microchanneled templates supporting the lowest levels of heterotopic bone formation. Taken together, these results demonstrate that 3D printed hypertrophic cartilage grafts represent a promising approach for the repair of complex bone fractures, particularly for larger defects where vascularisation will be a key challenge. (C) 2018 Elsevier Ltd. All rights reserved.