Drug evaluation based on 3D cell chip using various industrial 3D printing materials
다양한 산업용 3D 프린팅 소재를 사용한 3D 세포칩 기반 약물 평가
- 주제어 (키워드) cell chip , 3D cell culture , industrial material , 3D printing , drug evaluation
- 발행기관 서강대학교 일반대학원
- 지도교수 최정우
- 발행년도 2022
- 학위수여년월 2022. 2
- 학위명 박사
- 학과 및 전공 일반대학원 융합의생명공학과협동과정
- 실제 URI http://www.dcollection.net/handler/sogang/000000066439
- UCI I804:11029-000000066439
- 본문언어 영어
- 저작권 서강대학교 논문은 저작권 보호를 받습니다.
초록 (요약문)
2D cell culture models do not mimic the natural structures of tumors. While three-dimensional models such as three-dimensional (3D) scaffold better mimic the in vivo conditions for cell studies, tissue organization, and drug screening applications by comparison to conventional 2D models. Therefore, we investigated the possibility of cell culture by the surface modification of relatively low-cost industrial materials and an efficient 3D scaffold made with an industrial ABS filament for cell proliferation, spheroid formation, and drug screening applications. In the IA3D, spheroids of cancer HepG2 cells and keratinocytes HaCaT cells appeared after 2 and 3 days of culture, respectively, whereas no spheroids were formed in 2D culture. A gold nanoparticle-coated industrial ABS 3D scaffold (GIA3D) exhibited enhanced biocompatible properties, including increased spheroid formation by HepG2 cells compared to IA3D (1.3-fold) and 2D (38-fold) cultures. Furthermore, the cancer cells exhibited increased resistance to drug treatments in GIA3D, with cell viability of 122.9% in industrial GIA3D, 40.2% in IA3D, and 55.2% in 2D cultures when treated with 100 µM of mitoxantrone. Our results show that the newly engineered IA3D is an innovative 3D scaffold with upgraded properties for cell proliferation, spheroid formation, and drug-screening applications. Additionally, the optimal fabrication condition of the developed scaffold was used in the fabrication of the cell differentiation platform. We developed a new scaffold applied to the previous fabrication condition of the scaffold using new materials (industrial polylactic acid material). For improvement of cell adhesion ability and cell differentiation ability, we coated the IPTS to gold nanoparticles (AuNPs), NGF protein, peptide fragment NGF and sonic hedgehog (Shh) protein. The cell preparation of F3.Olig2 neural stem cells (NSCs) on surface-modified IPTS was increased in IPTS-AuNPs and IPTS-peptide fragment NGF compared with the IPTS group. The cells cultured on IPTS-shh protein showed high expression of motor neuron cell type-specific phenotypes such as HB9 and tubulin. Therefore, we suggest that the newly engineered industrial PLA scaffold is an innovative 3D scaffold for cell proliferation and differentiation. However, the problem of a single 3D cell culture platform cultured with one type of cell is that it is insufficient to represent the complex characteristics of the human body. A multi-channel integrated 3D single-cell culture platform can provide the ability to control the dynamic elements of the microenvironment and support the introduction of the mechanical and chemical signals missing from a single platform. We developed a multi-channel cell chip containing a 3D scaffold for horizontal co-culture and drug toxicity screening in multi-organ culture (human glioblastoma, cervical cancer, normal liver cells, and normal lung cells). The polydimethylsiloxane (PDMS) multi-channel cell chip (PMCCC) was based on fused deposition modeling (FDM) technology. We investigated cell proliferation and cytotoxicity by conducting 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays and analysis of OA-treated multi-channel cell chips. Taken together, the results demonstrated that the PMCCC might be used as a new 3D platform because it enables simultaneous drug screening in multiple cells by single-point injection and allows analysis of various biological processes.
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