Universal Efficient Dextran Microparticles Production with Microfluidic Technology

The use according to any one of the preceding claims, wherein the crosslinkable polymer comprises

• at least a polymer chain selected from a group consisting of PEG, dextran, gelatin, agarose, alginate, hyaluronic acid, collagen, proteins, polyacrylamide, block-polymers, at least an (C4-C12)alkylene chain, optionally substituted by one or two hydroxy group(s), or
• their mixtures,
• in particular PEG.

The use according to any one of the preceding claims, wherein the crosslinkable polymer is selected from a group consisting in a 2 to 12 arms polyethylene glycol thiol, dithiothreitol, dextran-SH, gelatin-SH, collagen-SH, proteins having at least two thiol functions and block-polymers having at least two thiol functions, in particular a PEG dithiol or a four-arm PEG thiol.

The use according to any one of the preceding claims, wherein the at least one synthetic or natural cell is selected from eukaryotic cells such as a mammalian cells, for instance human cells, prokaryotic cells such as bacterial cells or archaea cells, cancerous cells, tumoral cells, somatic cells, spleen cells, stem cells, progenitor cells, precursor cells, fully differentiated cells, undifferentiated cells, germ cells, cells of unicellular organism or of multi-cellular organism, fungal cells, splenocytes and hybridoma cell.

The use according to any one of the preceding claims, wherein the at least one synthetic or natural cell is selected from the group consisting of connective tissue cells, epithelial cells, muscle cells, blood cells, neuronal cells, endothelial cells, fibroblasts, keratinocytes, smooth muscle cells, stromal cells, mesenchymal cells, cord blood cells, embryonic stem cells, induced pluripotent stem cells (IPSc), patient-derived stem cells (PDSC), PDX cells (patient-derived xenograft cells), CDX cells (cell line-derived xenograft), biopsy samples cells, PDO cells (patient-derived organoid cells), placental cells, bone cells, bone marrow derived cells, immune system cells, hematopoietic cells, dendritic cells, hair follicle cells, chondrocytes, cardiomyocytes, hybridoma cells, cells from specific cell lines such as CHO cell, Jurkat cell, PreB cell, NK92 cell, THPIB cell, cell-free systems such as cell extract-based cell free systems and purified enzyme-based cell free systems and combinations thereof.

The use according to any one of the preceding claims, wherein the weight ratio of vinyl sulfone functionalized dextran and crosslinkable polymer having at least two thiol functions is comprised between 1% and 30%, in particular between 2% and 20%, particularly between 2.5% and 10%.

The use according to any one of the preceding claims, wherein the size of the modified dextran hydrogel microparticles is between 1 and 1000 μm, in particular between 1 μm and 999 μm, in particular between 10 and 500 μm, in particular between 30 and 180 μm.

The use according to any one of the preceding claims, wherein the modified dextran hydrogel microparticles has a coefficient of variation in size lower than 50%, in particular lower than 20%, and more particularly lower than 5%.

The use according to any one of the preceding claims, wherein it is aimed at cultivating said at least one synthetic or natural cell, for example as a 3D cell culture, in particular by incubating the microparticles in an environment suitable to allow for cell survival, cell growth, cell differentiation and/or cell proliferation such as clonal expansion, more particularly for producing a cell cluster, a spheroid, an organoid, a gastruloid, a tumoroid or a tissue.

Modified dextran hydrogel microparticles comprising (i) at least one vinyl sulfone functionalized dextran, (ii) at least one crosslinkable polymer having at least two thiol functions and (iii) at least one synthetic or natural cell, wherein

• the dextran has a molecular weight comprised between 5 and 500 kDa, and
• the substitution degree of the dextran by the vinyl sulfone is comprised between 5 and 60%, provided that the at least one crosslinkable polymer having at least two thiol functions is different from a crosslinkable polymer comprising dextran having a molecular weight comprised between 30 and 50 kDa as the polymer chain.