Microfluidic jet impact: Spreading, splashing, soft substrate deformation and injection.

HYPOTHESIS: Needle-free injections using microfluidic jets could be optimized by reducing splashing and controlling injection depth. However, this is impeded by an incomplete understanding on how jet characteristics influence impact outcome. We hypothesise that exploring the relation between microfluidic jet characteristics and substrate shear modulus on impact behavior will assist in predicting and giving insights on the impact outcome on skin and injection endpoints. EXPERIMENTS: To do so, a setup using microfluidic chips, at varying laser powers and stand-off distances, was used to create thermocavitation generated microfluidic jets with ranging characteristics (velocity: 7-77 m/s, diameter: 35-120 µm, Weber-number: 40-4000), which were impacted on substrates with different shear modulus. FINDINGS: Seven impact regimes were found, depending on jet Weber-number and substrate shear modulus, and we identified three thresholds: i) spreading/splashing threshold, ii) dimple formation threshold, and iii) plastic/elastic deformation threshold. The regimes show similarity to skin impact, although the opacity of skin complicated determining the threshold values. Additionally, we found that jet velocity has a higher predictive value for injection depth compared to the Weber-number, and consequently, the jet-diameter. Our findings provide fundamental knowledge on the interaction between microfluidic jets and substrates, and are relevant for optimizing needle-free injections.

Hydrogels derived from decellularized liver tissue support the growth and differentiation of cholangiocyte organoids.

Human cholangiocyte organoids are promising for regenerative medicine applications, such as repair of damaged bile ducts. However, organoids are typically cultured in mouse tumor-derived basement membrane extracts (BME), which is poorly defined, highly variable and limits the direct clinical applications of organoids in patients. Extracellular matrix (ECM)-derived hydrogels prepared from decellularized human or porcine livers are attractive alternative culture substrates. Here, the culture and expansion of human cholangiocyte organoids in liver ECM(LECM)-derived hydrogels is described. These hydrogels support proliferation of cholangiocyte organoids and maintain the cholangiocyte-like phenotype. The use of LECM hydrogels does not significantly alter the expression of selected genes or proteins, such as the cholangiocyte marker cytokeratin-7, and no species-specific effect is found between human or porcine LECM hydrogels. Proliferation rates of organoids cultured in LECM hydrogels are lower, but the differentiation capacity of the cholangiocyte organoids towards hepatocyte-like cells is not altered by the presence of tissue-specific ECM components. Moreover, human LECM extracts support the expansion of ICO in a dynamic culture set up without the need for laborious static culture of organoids in hydrogel domes. Liver ECM hydrogels can successfully replace tumor-derived BME and can potentially unlock the full clinical potential of human cholangiocyte organoids.