“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.