Additive Fertigung von mikrofluidischen Systemen zur Synthese von Mikrogelkapseln als Drug Delivery-System für angiogene Wachstumsfaktoren
Zusammenfassung der Projektergebnisse
In the project, we designed and fabricated a three-dimensional double emulsion device inside a microfluidic PDMS channel via in-chip direct laser writing (DLW). In-Chip DLW allowed for reproducible and relatively fast fabrication of droplet makers which mimicked the tips of opposing capillaries with orifice diameters down to 25 µm. The in-chip fabricated droplet makers enabled the generation of small water-polymer-water double emulsions down to 20 µm in outer diameters which are amongst the smallest double emulsion fabricated via dropletbased microfluidics. However, microgel capsules obtained from curing the shell of the double emulsions seemed relatively dense. In parallel, the polymer-properties of the microgel capsule shell were tuned. Here, a polymerization induced phase separation (PIPS) via the addition of octanol to the polymer-precursor solution was explored in a previously established microfluidic system. This highlighted the feasibility of these precursor solutions for facilitating the production of microgel capsules, capable of a diffusion-based release of biomolecules including the desired growth factors, relevant for an in vitro angiogenesis model. Dextran release studies and cell experiments with HUVECs conducted with capsules with different octanol amounts, showed the biocompatibility and growth factor release in capsules with 69 vol% octanol including EGM-2 + VEGF 500 ng/mL. These promising results will be further investigated and added in an angiogenesis in vitro model. The angiogenesis model shows that most GFs have a positive effect on vascularization in 3D co-cultures in PEG-based hydrogels in vitro with an optimal GF cocktail consists of Ang1, PDGF-BB and Ang2. To use our optimal growth factor combination (Ang1+PDGF/Ang2) in vivo, the microgel capsules that are loaded with GFs during microfluidic production, can then release the GFs at different time points depending on the shell properties. The first combination test of capsules in the angiogenesis model indicated that a low microgels number is needed to keep the hydrogel stable, which will be conducted in the future. Further, the explored droplet makers could be synergistically combined with the parallel-tested PIPS system for tuning the physical properties of the microgel capsules. This would present a promising approach for enhanced outcomes and potential advancements in future microgel capsule fabrication. The explored microgel capsules loaded with growth factors are promising candidates for temporally controlled release of growth factors, applicable in an angiogenesis model and beyond in diverse delivery systems.
Projektbezogene Publikationen (Auswahl)
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How Does Temporal and Sequential Delivery of Multiple Growth Factors Affect Vascularization Inside 3D Hydrogels?. Advanced Therapeutics, 7(1).
Bastard, Céline; Günther, Daniel; Gerardo‐Nava, José; Dewerchin, Mieke; Sprycha, Peter; Licht, Christopher; Lüken, Arne; Wessling, Matthias & De, Laporte Laura
