北京大学学报(医学版) ›› 2019, Vol. 51 ›› Issue (1): 115-119. doi: 10.19723/j.issn.1671-167X.2019.01.021

• 论著 • 上一篇    下一篇

骨组织工程支架3D打印系统的建立与支架宏微结构精度的可控性评价

李榕1,陈科龙2,王勇1,刘云松1,周永胜1,(),孙玉春1,()   

  1. 1. 北京大学口腔医学院·口腔医院,口腔医学数字化研究中心,口腔修复教研室 国家口腔疾病临床医学研究中心 口腔数字化医疗技术和材料国家工程实验室 口腔数字医学北京市重点实验室, 北京 100081
    2. 北京实诺泰克科技有限公司, 北京 100080
  • 收稿日期:2017-05-06 出版日期:2019-02-18 发布日期:2019-02-26
  • 通讯作者: 周永胜,孙玉春 E-mail:kqzhouysh@hsc.pku.edu.cn;polarshining@163.com
  • 基金资助:
    国家自然科学基金(51475004);国家重点研发计划(2016YFC1102900);科技北京百名领军人才培养工程(Z171100001117169);北京大学医学部-英国伦敦国王学院医学研究联合研究所联合研究项目

Establishment of a 3D printing system for bone tissue engineering scaffold fabrication and the evaluation of its controllability over macro and micro structure precision

Rong LI1,Ke-long CHEN2,Yong WANG1,Yun-song LIU1,Yong-sheng ZHOU1,(),Yu-chun SUN1,()   

  1. 1. Center for Digital Dentistry, Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
    2. Shinotech Co., Ltd, Beijing 100080, China
  • Received:2017-05-06 Online:2019-02-18 Published:2019-02-26
  • Contact: Yong-sheng ZHOU,Yu-chun SUN E-mail:kqzhouysh@hsc.pku.edu.cn;polarshining@163.com
  • Supported by:
    Supported by the National Natural Science Foundation of China(51475004);the National Key Research and Development Program of China(2016YFC1102900);the Project for Culturing Leading Talents in Scientific and Technological Innovation of Beijing(Z171100001117169);and Joint Grant from PKUHSC-KCL Joint Institute for Medical Research

摘要:

目的:自主研发一种基于熔融沉积成形原理的骨组织工程支架3D打印系统,定量评价其打印聚乳酸(polylactide,PLA)、聚己内酯(polycaprolactone, PCL)制件的宏观和微观结构精度可控性。方法:系统硬件部分为基于三轴步进电机控制的单喷头熔融挤出材料的混元-Ⅰ型生物打印机,喷头直径为0.3 mm,配套打印分层软件生成打印控制代码为Gcode格式文件。用Imageware设计长×宽×高为10 mm×10 mm×2 mm的长方体,保存成STL文件。将文件导入配套打印分层软件并设定长方体内部为均匀分布的长方体孔隙结构,打印层厚0.2 mm,生成Gcode代码并用混元-Ⅰ型生物打印机分别打印PLA和PCL制件,每种材料重复打印10次。打印完成并充分自然冷却后取下,获得PLA、PCL打印制件(10个×2组)。用游标卡尺测量每个制件的宏观尺寸,每组任意选取3个制件用激光三维形貌测量显微镜扫描并测量每个制件层间重叠和无层间重叠区域的孔隙尺寸与实体支撑梁的直径。结果:所建立系统打印的PLA、PCL制件孔隙规则且相互贯通,宏观尺寸分别为PLA:长 9.950(0.020) mm,宽 9.950(0.003) mm,高 1.970(0.023) mm;PCL:长 9.845(0.025) mm,宽 9.845(0.045) mm,高 1.950(0.043) mm。内部结构PLA、PCL层间重叠部分支撑梁直径稍有增粗,前者较明显。各测量值中PLA层间重叠区域孔隙(274.09±8.35) μm与设计值差值最大,为26.91 μm。结论:应用自主研发的组织工程支架3D打印系统可完成PLA、PCL多孔支架的打印,该系统对宏观、微观结构的可控性满足研究应用需求。

关键词: 骨组织工程, 支架, 聚乳酸, 聚己内酯, 熔融沉积成形

Abstract:

Objective: To establish a 3D printing system for bone tissue engineering scaffold fabrication based on the principle of fused deposition modeling, and to evaluate the controllability over macro and micro structure precision of polylactide (PLA) and polycaprolactone (PCL)scaffolds. Methods: The system was composed of the elements mixture-Ⅰ bioprinter and its supporting slicing software which generated printing control code in the G code file format. With a diameter of 0.3 mm, the nozzle of the bioprinter was controlled by a triaxial stepper motor and extruded melting material. In this study, a 10 mm×10 mm×2 mm cuboid CAD model was designed in the image ware software and saved as STL file. The file was imported into the slicing software and the internal structure was designed in a pattern of cuboid pore uniform distribution, with a layer thickness of 0.2 mm. Then the data were exported as Gcode file and ready for printing. Both polylactic acid (PLA) and polycaprolactone (PCL) filaments were used to print the cuboid parts and each material was printed 10 times repeatedly. After natural cooling, the PLA and PCL scaffolds were removed fromthe platform and the macro dimensions of each one were measured using a vernier caliper. Three scaffolds of each material were randomly selected and scanned by a 3D measurement laser microscope. Measurements of thediameter of struts and the size of pores both in the interlayer overlapping area and non-interlayer overlapping area were taken. Results: The pores in the printed PLA and PCL scaffolds were regular and interconnected. The printed PLA scaffolds were 9.950 (0.020) mm long, 9.950 (0.003) mm wide and 1.970 (0.023) mm high, while the PCL scaffolds were 9.845 (0.025) mm long, 9.845 (0.045) mm wide and 1.950 (0.043) mm high. The struts of both the PLA and PCL parts became wider inthe interlayer overlapping area, and the former was more obvious. The difference between the designed size and the printed size was greatest in the pore size of the PLA scaffolds in interlayer overlapping area [(274.09 ± 8.35) μm)], which was 26.91 μm. However, it satisfied the requirements for research application. Conclusion: The self-established 3D printing system for bone tissue engineering scaffold can be used to print PLA and PCL porous scaffolds. The controllability of this system over macro and micro structure can meet the precision requirements for research application.

Key words: Bone tissue engineering, Scaffold, Polylactide, Polycaprolactone, Fused deposition modeling

中图分类号: 

  • R78

图1

长方体CAD模型(长×宽×高为10 mm×10 mm×2 mm)"

图2

配套打印分层软件生成的打印规划路径"

图3

混元-Ⅰ型生物打印机打印的长方体制件"

表1

PLA和PCL打印制件宏观尺寸及差异[中位数(四分位距)]"

Items PLA/mm PCL/mm Kolmogorov-Smirnov Z value P value
Length 9.950 (0.020) 9.845 (0.025) 2.236 0.000
Width 9.950 (0.003) 9.845 (0.045) 2.236 0.000
Height 1.970 (0.023) 1.950 (0.043) 0.894 0.400

图4

打印长方体制件的扫描图像(×200)"

表2

打印制件水平方向内部结构尺寸及差异(x?±s)"

Items PLA/μm PCL/μm t value P value Difference value of mean (PLA-PCL) 95% confidence interval
Pore 1 297.99±6.89 297.87±3.02 0.064 0.949 0.11 -3.49-3.72
Strut 1 295.90±4.59 291.97±3.75 2.813 0.008 3.93 1.09-6.77
Pore 2 274.09±8.35 281.96±5.34 -3.367 0.002 -7.87 -12.61--3.12
Strut 2 321.12±5.74 303.63±5.12 9.641 0.000 17.49 13.80-21.17

图5

手术刀切割后的打印长方体制件垂直截面扫描激光显示图(放大倍数 ×200)"

图6

仅由两层实体支撑梁组成的结构的扫描3D显示图(放大倍数 ×200)"

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