Supplementary Material for: “Islet-On-a-Chip” – a microfluidic system design for preservation of viability and function of human islets of Langerhans: a systematic review

Purpose: There are multiple designs of microfluidic devices to study islets of Langerhans in vitro. There is an ongoing debate which design of microfluidic device is optimal in maintaining highest viability and function of the islets in vitro.
Methods. A systematic literature review was conducted to evaluate the most common designs used of microfluidic devices to culture human pancreatic islets in vitro. The review included the following microfluidic designs: microwell, hanging drop, hydrodynamic trap, encapsulation and hydrogel scaffolds. PubMed and Google Scholar databases were searched for all relevant studies (articles in English; case studies were excluded, reference period January 2013 – June 2023). Data on islet function (insulin stimulation index) and viability, duration of experiment, design of microfluidic device and type of cells in the experiment were collected. ANOVA was utilized for statistical analysis.
Results. A total of 1646 studies were identified in the electronic database search. There were 310 duplications, 1152 studies were excluded after the initial screening, additionally 143 studies were excluded after reading a full - text article. 41 studies were included in the final analysis. The highest viability was reported in hydrogel scaffold group - 97 % (one study), followed by hydrodynamic trap 93,0 % (± 4,2), microwell 89,2 % (± 10,1), encapsulation 88,7 % (± 6,3) accordingly. ANOVA showed no difference among the designs (F=0.434, df 3,29, p = 0.731). The highest insulin stimulation index was observed in hanging drop microfluidic devices 8,5 (± 4,9), followed by microwell 2,94 (± 1,1), hydrogel scaffolds 2,9 (± 0,6), hydrodynamic trap 2.09 (± 1,0), encapsulation 1.81 (± 1,0). After utilizing ANOVA test, significant differences among the mean values of ISI were observed (F=8,826 (df 3,35), p <0,001)
Conclusion. Hydrogel scaffold design of microfluidic devices might be associated with the highest viability of islets, and islet function is best preserved by hanging drop systems. More research is needed to further investigate the optimal design for further islet viability and function in vitro.

研究背景：当前已有多种微流控设备（microfluidic devices）用于体外研究朗格汉斯岛（即胰岛，islets of Langerhans），但学界对于哪种微流控设备设计可最优维持胰岛的体外活性与功能仍存在持续争议。
研究方法：本研究通过系统文献综述，评估用于体外培养人胰腺胰岛的主流微流控设备设计类型，所纳入的微流控设计包括微孔（microwell）、悬滴（hanging drop）、流体动力捕获装置（hydrodynamic trap）、包埋法（encapsulation）及水凝胶支架（hydrogel scaffolds）。检索PubMed与Google Scholar数据库，筛选2013年1月至2023年6月期间发表的英文相关研究（排除病例研究）。本研究收集的数据包括胰岛功能（胰岛素刺激指数，insulin stimulation index, ISI）与活性、实验周期、微流控设备设计类型及实验所用细胞类型，并采用方差分析（Analysis of Variance, ANOVA）进行统计学分析。
研究结果：本研究通过电子数据库检索共识别出1646项相关研究，其中310项为重复研究，初筛阶段排除1152项，通读全文后进一步排除143项，最终纳入41项研究进行最终分析。结果显示，水凝胶支架组的胰岛活性最高，达97%（仅1项研究）；其次为流体动力捕获装置组（93.0% ±4.2）、微孔组（89.2% ±10.1）及包埋组（88.7% ±6.3）。方差分析结果表明，各组胰岛活性无显著差异（F=0.434，df=3,29，p=0.731）。在胰岛素刺激指数方面，悬滴式微流控设备组表现最优，均值为8.5（±4.9）；其次为微孔组（2.94 ±1.1）、水凝胶支架组（2.9 ±0.6）、流体动力捕获装置组（2.09 ±1.0）及包埋组（1.81 ±1.0）。方差分析结果显示，各组胰岛素刺激指数的均值存在显著差异（F=8.826，df=3,35，p<0.001）。
研究结论：微流控设备的水凝胶支架设计或可实现最高的胰岛活性，而悬滴系统可最优维持胰岛功能。未来仍需开展更多研究，以进一步明确体外培养胰岛的最优设备设计，兼顾胰岛活性与功能。