PT  - JOURNAL ARTICLE
AU  - Zhongliang Jiang
AU  - Fang-Yi Lin
AU  - Kun Jiang
AU  - Han Nguyen
AU  - Chun-Yi Chang
AU  - Chien-Chi Lin
TI  - Dissolvable microgel-templated macroporous hydrogels for controlled cell assembly
AID  - 10.1101/2022.01.05.475155
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.05.475155
4099  - http://biorxiv.org/content/early/2022/01/06/2022.01.05.475155.short
4100  - http://biorxiv.org/content/early/2022/01/06/2022.01.05.475155.full
AB  - Mesenchymal stem cells (MSCs)-based therapies have been widely used to promote tissue regeneration and to modulate immune/inflammatory response. The therapeutic potential of MSCs can be further improved by forming multi-cellular spheroids. Meanwhile, hydrogels with macroporous structures are advantageous for improving mass transport properties for the cell-laden matrices. Herein, we report the fabrication of MSC-laden macroporous hydrogel scaffolds through incorporating rapidly dissolvable spherical cell-laden microgels. Dissolvable microgels were fabricated by tandem droplet-microfluidics and thiol-norbornene photopolymerization using a novel fast-degrading macromer poly(ethylene glycol)-norbornene-dopamine (PEGNB-Dopa). The cell-laden microgels were subsequently encapsulated within another bulk hydrogel matrix, whose porous structure was generated efficiently by the rapid degradation of the PEGNB-Dopa microgels. The cytocompatibility of this in situ pore-forming approach was demonstrated with multiple cell types. Furthermore, adjusting the stiffness and cell adhesiveness of the bulk hydrogels afforded the formation of solid cell spheroids or hollow spheres. The assembly of solid or hollow MSC spheroids led to differential activation of AKT pathway. Finally, MSCs solid spheroids formed in situ within the macroporous hydrogels exhibited robust secretion of HGF, VEGF-A, IL-6, IL-8, and TIMP-2. In summary, this platform provides an innovative method for forming cell-laden macroporous hydrogels for a variety of future biomedical applications.Competing Interest StatementChien-Chi Lin and Fang-Yi Lin are the inventors of the rapidly degrading PEGNB-Dopa hydrogel technology. A US provisional patent (#63/147,152) has been filed on Feb 8, 2021.