Centre for Additive Manufacturing, Faculty of Engineering, University of Nottingham, University Park, Nottingham NG7 2RD, UK; Regenerative Medicine and Cellular Therapies Division, Faculty of Science, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Wolfson School of Mechanical, Electrical and Manufacturing Engineering, University of Loughborough, Loughborough LE113TU, UK.
Mater Sci Eng C Mater Biol Appl. 2020 Apr;109:110578. doi: 10.1016/j.msec.2019.110578. Epub 2019 Dec 20.
The current gold standard for nasal reconstruction after rhinectomy or severe trauma includes transposition of autologous cartilage grafts in conjunction with coverage using an autologous skin flap. Harvesting autologous cartilage requires a major additional procedure that may create donor site morbidity. Major nasal reconstruction also requires sculpting autologous cartilages to form a cartilage framework, which is complex, highly skill-demanding and very time consuming. These limitations have prompted facial reconstructive surgeons to explore different techniques such as tissue engineered cartilage. This work explores the use of multi-material 3D bioprinting with chondrocyte-laden gelatin methacrylate (GelMA) and polycaprolactone (PCL) to fabricate constructs that can potentially be used for nasal reconstruction. In this study, we have investigated the effect of 3D manufacturing parameters including temperature, needle gauge, UV exposure time, and cell carrier formulation (GelMA) on the viability and functionality of chondrocytes in bioprinted constructs. Furthermore, we printed chondrocyte-laden GelMA and PCL into composite constructs to combine biological and mechanical properties. It was found that 20% w/v GelMA was the best concentration for the 3D bioprinting of the chondrocytes without comprising the scaffold's porous structure and cell functionality. In addition, the 3D bioprinted constructs showed neocartilage formation and similar mechanical properties to nasal alar cartilage after a 50-day culture period. Neocartilage formation was also observed in the composite constructs evidenced by the presence of glycosaminoglycans and collagen type II. This study shows the feasibility of manufacturing neocartilage using chondrocytes/GelMA/PCL 3D bioprinted porous constructs which could be applied as a method for fabricating implants for nose reconstruction.
目前,鼻再造术或严重创伤后,金标准包括自体软骨移植物的转位与自体皮瓣覆盖相结合。自体软骨采集需要一个主要的附加程序,可能会造成供体部位的发病率。主要的鼻重建还需要雕刻自体软骨形成软骨框架,这是复杂的,高度需要技能和非常耗时。这些限制促使面部重建外科医生探索不同的技术,如组织工程软骨。这项工作探索了使用多材料 3D 生物打印与软骨细胞负载的明胶甲基丙烯酸酯(GelMA)和聚己内酯(PCL)制造可以潜在用于鼻重建的构建体。在这项研究中,我们研究了 3D 制造参数,包括温度、针规、UV 暴露时间和细胞载体配方(GelMA)对生物打印构建体中软骨细胞的活力和功能的影响。此外,我们打印了负载软骨细胞的 GelMA 和 PCL 到复合构建体中,以结合生物和机械性能。结果发现,20%w/v GelMA 是 3D 打印软骨细胞的最佳浓度,不会影响支架的多孔结构和细胞功能。此外,3D 生物打印的构建体在 50 天的培养期后表现出新生软骨形成和类似于鼻翼软骨的机械性能。在复合构建体中也观察到了新生软骨的形成,这是由糖胺聚糖和 II 型胶原的存在证明的。这项研究表明使用软骨细胞/GelMA/PCL 3D 生物打印多孔构建体制造新生软骨的可行性,这可能作为制造鼻重建植入物的一种方法。