Droplet Microfluidics-Based Fabrication of Monodisperse Poly(ethylene glycol)-Fibrinogen Breast Cancer Microspheres for Automated Drug Screening Applications

自愈水凝胶 药物输送 乙二醇 癌细胞 微流控 材料科学 纳米技术 三维细胞培养 癌症 组织工程 生物物理学 生物医学工程 细胞 化学 生物化学 生物 医学 有机化学 高分子化学 遗传学
作者
Wen J. Seeto,Yuan Tian,Shantanu Pradhan,Dmitriy Minond,Elizabeth A. Lipke
出处
期刊:ACS Biomaterials Science & Engineering [American Chemical Society]
卷期号:8 (9): 3831-3841 被引量:5
标识
DOI:10.1021/acsbiomaterials.2c00285
摘要

Spheroidal cancer microtissues are highly advantageous for a wide range of biomedical applications, including high-throughput drug screening, multiplexed target validation, mechanistic investigation of tumor-extracellular matrix (ECM) interactions, among others. Current techniques for spheroidal tissue formation rely heavily on self-aggregation of single cancer cells and have substantial limitations in terms of cell-type-specific heterogeneities, uniformity, ease of production and handling, and most importantly, mimicking the complex native tumor microenvironmental conditions in simplistic models. These constraints can be overcome by using engineered tunable hydrogels that closely mimic the tumor ECM and elucidate pathologically relevant cell behavior, coupled with microfluidics-based high-throughput fabrication technologies to encapsulate cells and create cancer microtissues. In this study, we employ biosynthetic hybrid hydrogels composed of poly(ethylene glycol diacrylate) (PEGDA) covalently conjugated to natural protein (fibrinogen) (PEG-fibrinogen, PF) to create monodisperse microspheres encapsulating breast cancer cells for 3D culture and tumorigenic characterization. A previously developed droplet-based microfluidic system is used for rapid, facile, and reproducible fabrication of uniform cancer microspheres with either MCF7 or MDA-MB-231 (metastatic) breast cancer cells. Cancer cell-type-dependent variations in cell viability, metabolic activity, and 3D morphology, as well as microsphere stiffness, are quantified over time. Particularly, MCF7 cells grew as tight cellular clusters in the PF microspheres, characteristic of their epithelial morphology, while MDA-MB-231 cells displayed elongated and invasive morphology, characteristic of their mesenchymal and metastatic nature. Finally, the translational potential of the cancer microsphere platform toward high-throughput drug screening is also demonstrated. With high uniformity, scalability, and control over engineered microenvironments, the established cancer microsphere model can be potentially used for mechanistic studies, fabrication of modular cancer microtissues, and future drug-testing applications.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
1秒前
快乐嚓茶发布了新的文献求助10
2秒前
顾矜应助张狗蛋采纳,获得10
2秒前
来了发布了新的文献求助10
3秒前
838915882蒽发布了新的文献求助10
5秒前
5秒前
个性的紫菜应助秋月明采纳,获得10
7秒前
李健应助wyyy采纳,获得10
7秒前
万能图书馆应助浅浅殇采纳,获得10
7秒前
风中莫英完成签到 ,获得积分10
12秒前
来了完成签到,获得积分20
13秒前
折磊磊发布了新的文献求助10
14秒前
Nnn完成签到,获得积分10
19秒前
玉麒麟完成签到,获得积分10
22秒前
23秒前
24秒前
NexusExplorer应助佳佳佳佳采纳,获得10
25秒前
Owen应助xiaoxiao采纳,获得30
26秒前
hanliulaixi发布了新的文献求助10
27秒前
27秒前
Akim应助overThat采纳,获得10
31秒前
小马完成签到 ,获得积分10
31秒前
31秒前
852应助书枫哥哥采纳,获得10
31秒前
34秒前
34秒前
圆圆圆完成签到,获得积分10
35秒前
37秒前
大方的以南应助steph33采纳,获得10
38秒前
38秒前
佳佳佳佳发布了新的文献求助10
38秒前
wanci应助畅快手套采纳,获得10
39秒前
折磊磊发布了新的文献求助10
40秒前
xiaoxiao发布了新的文献求助30
42秒前
overThat发布了新的文献求助10
42秒前
领导范儿应助百宝采纳,获得10
43秒前
yxw发布了新的文献求助10
44秒前
英俊的铭应助wwl采纳,获得10
44秒前
科研小白完成签到,获得积分10
45秒前
高分求助中
The three stars each: the Astrolabes and related texts 1120
Electronic Structure Calculations and Structure-Property Relationships on Aromatic Nitro Compounds 500
Revolutions 400
Psychological Warfare Operations at Lower Echelons in the Eighth Army, July 1952 – July 1953 400
宋、元、明、清时期“把/将”字句研究 300
Julia Lovell - Maoism: a global history 300
转录因子AP-1抑制T细胞抗肿瘤免疫的机制 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 有机化学 工程类 生物化学 纳米技术 物理 内科学 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 电极 光电子学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 2437435
求助须知:如何正确求助?哪些是违规求助? 2117233
关于积分的说明 5375363
捐赠科研通 1845299
什么是DOI,文献DOI怎么找? 918287
版权声明 561700
科研通“疑难数据库(出版商)”最低求助积分说明 491250