CAD-assisted printing path generation for 3D biomedical printing technique and its applications = 3차원 바이오메디컬 프린팅 기술을 위한 CAD 기반 프린팅 경로 생성과 이의 적용

다국어 초록 (Multilingual Abstract)

3D printing technique has been considered as a new industrial revolution because it has led to the flexible and rapid production of highly customized free-form structure without spending time and cost to modify or organize manufacturing tools and process. Possessing above-mentioned advantages, 3D printing is having a tremendous impact on tissue engineering and medical fields. 3D printing enables not only the production of implants well aligned with individual patient’s unique anatomy and defect, but also engineering design and fabrication of scaffold for tissue regeneration.
Production of personalized products and complex structures using 3D printing is fundamentally facilitated with a help of advanced design and measurement tools of computer-aided design and manufacturing (CAD/CAM) system, which briefly includes designing of the 3D model with controlled interior and exterior scaffold structure using CAD tools, and transferring the model into the 3D printing machine via printing path generation algorithm. One of the major approaches to obtain 3D model is the use of powerful 3D modelling tools of commercial CAD software, but the printing path generation algorithm should be different according to scaffold design, the specific target tissue, and the 3D printing apparatus.
Herein, we developed algorithms to control previously and newly developed 3D printing systems for various tissue engineering and clinical applications assisted with CAD/CAM technology, and demonstrated efficient procedures for constructs engineering based on the achievements. The Computerized Numerical Control (CNC) code generated by the developed algorithms with 3D CAD model information and user-input parameters were transferred into 3D printing systems. The algorithms with 3D printing systems facilitated design and optimization of pore architectures, clinical applications to repair two patients with an arhinia and a depressed malar region, and production of cell-laden constructs with the desired shape. These results indicated that we could now address difficult challenges, including customized interior and exterior architecture, cell positioning into 3D structure, and heterogeneous and large volume tissue printing with choosing or modifying an appropriate algorithm, 3D printing system and CAD/CAM procedure.

국문 초록 (Abstract)

3차원 프린팅 기술은 근래에 가장 획기적인 산업 기술로 여겨지고 있으며, 다양한 3차원 구조체를 공정 변경이나 개선 등의 어려움 없이 신속하고 편리하게 제작할 수 있는 강점이 있다. 이는 다양한 산업 시장의 신속한 맞춤형 제작의 요구를 충족시킬 수 있으며, 특히 의료 분야에서 환자 맞춤형 임플란트 기술 개발에 큰 기여를 할 것으로 기대되고 있다. 또한 절삭, 밀링 등의 기존 가공기술에서는 어려운 복잡한 3차원 내부 구조를 3차원 프린팅을 이용해 쉽고 간편하게 재현할 수 있어, 조직공학 용 인공지지체 개발에서도 많은 각광을 받고 있다.
3차원 프린팅을 이용한 맞춤형 또는 복잡한 형상의 재현은 Computer-aided design and manufacturing (CAD/CAM) 기술을 통해 달성될 수 있다. 이는 CAD 모델 설계, 3차원 프린팅 머신의 제어를 위한 명령 코드 (Computerized Numerical Control, CNC) 로의 변환을 포함한다. 이때 프린팅 경로생성 알고리즘을 통해 설계된 CAD model이 프린팅 머신의 특성, 재현될 구조의 특성에 맞추어 자동적으로 CNC 코드로 변환하는 작업을 수행한다. CAD/CAM 기술에서 CAD 모델 설계에서는 다양하고 우수한 설계 도구를 포함한 상용화된 CAD 제품을 쓰는 것이 합리적이지만, 이를 CNC code로 변환하는 것은 재현할 구조 특성과 머신의 특성이 같이 반영되어야 하기 때문에 상황에 맞는 프린팅 경로생성 알고리즘이 요구된다.
본 연구에서는 이전 또는 새롭게 개발된 3차원 프린팅 머신과 그 목적에 맞추어 프린팅 경로생성 알고리즘을 개발하였으며, 이를 통해 다양한 구조설계 방법과 적용 사례를 제시하였다. 개발된 프린팅 경로생성 알고리즘은 상용화된 CAD 제품을 통해 설계된 모델에 기반하여 장비 제어와 관련된 수치를 입력하여 CNC 코드를 생성하는 방식을 따른다. 이 기술은 타깃 조직 또는 기관에 적합한 맞춤형 내/외부 구조 설계를 가능하게 하였으며, 특히 다른 신체적 결함을 지닌 두 환자를 위한 맞춤형 구조체를 제작하는 성과를 얻을 수 있었다. 또한 3차원 세포 프린팅을 통한 전례 없는 세포의 맞춤형 프린팅과 이를 통한 인체 기관 및 조직 모방형 대면적의 제작에 성공하였다. 이와 같이 프린팅 경로생성 알고리즘을 통해 진보된 CAD/CAM 기술이 가능함을 증명하였으며, 이는 향후에 많은 임상적, 조직공학적 연구에 기반기술로서 활용될 것이다.

목차 (Table of Contents)

• List of Tables VIII
• List of Figures IX
• I Introduction 1
• 1.1 Scaffolding in tissue engineering 1
• 1.2 Role of CAD/CAM system in design/fabrication of scaffolds 2
• 1.3 Research objective 4
• 1.4 Thesis organization 6
• II Development of Printing Path Generation Algorithms for 3D Biomedical Printing Technique 8
• 2.1 Introduction 8
• 2.2 Computer-aided scaffold architecture design approach 9
• 2.2.1 Specific exterior shape design 9
• 2.2.2 Scaffold pore architecture design 10
• 2.3 Printing path generation algorithm for line drawing-based 3D printing approach 11
• 2.3.1 Overview of line drawing-based 3D printing approach to form porous architecture 11
• 2.3.2 Slicing algorithm from STL file data 12
• 2.3.3 Printing path generation algorithm 15
• 2.3.4 Printing path generation algorithm for creation of a scaffold with triangular pore pattern 16
• 2.4 Projection image generation algorithm for image projection-based 3D printing system 18
• 2.4.1 Overview of projection-based microstereolithography (pMSTL) 18
• 2.4.2 Projection image generation algorithm 18
• 2.4.3 3D scaffold architecture design and fabrication in pMSTL system 20
• 2.5 Conclusion 21
• III CAD/CAM-based Design of 3D Pore Architecture of a Scaffold and its Estimation 22
• 3.1 Introduction 22
• 3.2 Effect of a scaffold pore architecture on the diffusivity 23
• 3.2.1 Oxygen diffusion in scaffold 23
• 3.2.2 Numerical analysis approach for evaluating effective diffusivities of scaffolds with various pore architecture 25
• 3.2.3 Experimental verification 31
• 3.3 Effect of a scaffold pore architecture on the mechanical behavior 35
• 3.3.1 Mechanical requirements of a scaffold for tissue regeneration 35
• 3.3.2 Design and fabrication of a scaffold with 3D pore architecture 36
• 3.3.3 Measurement of mechanical behavior of scaffolds 40
• 3.4 Conclusion 42
• IV CAD/CAM-based Design of Customized Exterior Shape for Medical Applications 44
• 4.1 Introduction 44
• 4.2 Nasal reconstruction using a customized 3D-printed nasal stent for congenital arhinia 46
• 4.2.1 Introduction to arhinia 46
• 4.2.2 Nasal reconstruction for an arhinia patient and necessity of 3D printing technology 47
• 4.2.3 Customized stent design and 3D printing 49
• 4.2.4 Surgical processes during nose reconstruction 52
• 4.2.5 Discussion 54
• 4.3 3D printing of customized implant for reconstruction of depressed malar bone 56
• 4.3.1 Review of a patient with depressed malar bone 56
• 4.3.2 Design of a customized implant 57
• 4.3.3 Fabrication of the implant scaffold 58
• 4.3.4 Implantation of the scaffold and regenerative results 60
• 4.3.5 Discussion 61
• 4.4 Conclusion 61
• V CAD/CAM-based 3D Printing Technology for Production of Cell-laden Constructs 63
• 5.1 Introduction 63
• 5.2 Computer-aided multiple-head 3D printing system for printing of heterogeneous organ/tissue constructs 65
• 5.2.1 Introduction to direct cell printing using multiple-head 3D printing system 65
• 5.2.2 Overall process of the algorithm to generate printing-paths for 3D printing of heterogeneous tissue 67
• 5.2.3 Multiple-head 3D printing of 3D heterogeneous tissue constructs 72
• 5.2.4 Discussion 74
• 5.3 Computer-aided Cartilage Tissue Engineering for Rhinoplasty Application 76
• 5.3.1 Background and objective 76
• 5.3.2 Preparation of materials for injection technique 77
• 5.3.3 Injection of cell-hydrogel solution to the nasal implant-shaped porous frame 80
• 5.3.4 Evaluation of hASC-cdECM hydrogel and injection technique for rhinoplasty application 81
• 5.3.4.1 Cell viability within the hydrogel injected into the frame 81
• 5.3.4.2 In vitro evaluation of chondrogenic potential of hASC within cdECM hydrogel 82
• 5.3.4.3 In vivo evaluation of validity of hASCs-cdECM hydrogel construct with nasal implant shape for rhinoplasty application 86
• 5.3.5 Discussion 89
• 5.4 Conclusion 90
• VI Conclusion and Future Works 92
• 6.1 Conclusion 92
• 6.2 Future works 94
• 한글 요약문(Summary in Korean) 96
• References 99