Table 1.
Reports on the use of microfluidics in bioprinting (P) and in producing cell-laden microfibers (F) using microchannel-based (C) or needle-based (N) systems. Studies showing cell types, biomaterials, and fabrication methods. (*) Injection, not conventional microfluidic bioprinting.
| Study | Cells | Biomaterial | Method | P/F | C/N | Tissue | Ref. |
|---|---|---|---|---|---|---|---|
| Production of cell-loaded microfibers | Bovine carotid artery vascular endotelial cells (ECs) | Alginate | Needle extrusion of alginate in co-flowing stream of CaCl2 | F | N | Not specific | [285] |
| A novel microfluidic-based technique for continuous formation of microfibers | Human fibroblasts; Bovine serum albumin (model for biomolecules) | Alginate | Microfluidic co-axial flow of alginate in the core and CaCl2 in the sheath | F | C | Not specific | [286] |
| Formation of cell-laden tubular hydrogels in laminar flow stream | Human kidney 293 cells | Alginate | Microfabricated silicon nozzle array is used to simultaneously produce multiple microfibers by extruding alginate solution into a stream of CaCl2 solution | F | N/A (micro-nozzle (MN) array) | Not specific | [287] |
| Fabrication of 3D architected tissue constructs to be utilized as pharmacokinetic models | Hepatocytes HepG2 | Alginate | Syringe-based direct cell writing (DCW) is used to fabricate 3D micro-organ and is followed by soft lithographic micropatterning to create in vitro device | P | N | Not specific | [288] |
| Fabrication of cell-laden alginate hollow fibers | Human iliac vein endothelial cells (HIVE-78); Bovine serum albumin (model for biomolecules) | Alginate | Microfluidic chip and co-axial flow | F | C | Not specific | [289] |
| Formation of alginate microfibers | E. coli; yeast | Alginate, carboxylate polymer beads and silver nanoparticles | Roller-assisted microfluidic system (forming by microfluidic chip into a CaCl2 bath) | F | C | Not specific | [182] |
| Fabrication of scaffold-free vascular tubular grafts | Various vascular cell types, including smooth muscle cells (SMCs) and fibroblasts | Agarose rods and multicellular spheroids | Computer-aided bioprinting with separate printheads for extrusion of agarose rods and multicellular cylinders | P | N/A (micropipette) | Not specific | [129] |
| Vessel-like cell-laden constructs | NIH 3T3 fibroblasts | Cell-laden TetraPAc-crosslinked synthetic extracellular matrices (sECMs), polyethylene glycol diacrylate (PEGDA)-crosslinked sECMs, and acellular agarose macrofilaments | Microcapillary tube extrusion system | P | N/A (microcapillary tube) | blood vessel | [130] |
| Cell-laden microfibers | Human hepatocellular carcinoma (HepG2) | Alginate or Alginate-chitosan | Co-axial flow microfluidic chip | F | C | Not specific | [77] |
| Cell-laden microfibers0 | Wharton’s Jelly mesenchymal stem cells (MSCs); human myeloid leukemia K562 cells | Alginate | Forming by microfluidic chip into a BaCl2 bath | F | C | Not specific | [290] |
| Microfluidic fabrication of cell-laden continuous fibers | Hepatocytes; fibroblasts; Embryonic neural cells (on surface); Neutrophil culture | Alginate | Microfluidic system with several independently controllable inlets | F | C | Not specific | [291] |
| Microfluidic fabrication of hydrogel microfibers for guided cell growth and networking | Fibroblasts (3T3); human cervical cancer cell line (HeLa); rat pheochromocytoma cell line (PC12) | Cell laden soft core (alginate) sandwiched between solid layers of propylene glycol alginate (PGAL) , surrounded by poly-L-lysine (PLL) membrane | PDMS microchannel with separate inlets for sodium alginate solutions with cells in core and without cells in shell | F | C | Not specific | [233] |
| Microfibers loaded with hepatocytes at center sandwiched by 3T3 cells | Hepatocytes; 3T3 fibroblasts | Alginate | PDMS microchannel with separate inlets for suspensions of sodium alginate with 3T3 cells and hepatocytes | F | C | liver tissues | [188] |
| 3D alginate constructs | N/A | Alginate | 3D printing by co-axial flow focusing microfluidic printhead | P | C | Not specific | [79] |
| Developing a microfluidic-based 3D bioprinter with on-the-fly multimaterial switching capability | N/A | Alginate | 3D printing by co-axial flow focusing microfluidic printhead | P | C | Not specific | [80] |
| Microfluidic production of long cell-laden core-shell fibers | Fibroblasts (NIH/3T3); myocytes (C2C12, CM (rat primary)); endothelial cells (HUVEC (human primary), MS1); nerve cells (cortical cells (rat primary), neural stem cells (mouse primary)); epithelial cells(HepG2, MIN6m9, HeLa) | Shell is alginate. Core is either pepsin-solubilized type-I collagen (PCol), or acid-solubilized type-I collagen (ACol), or fibrin | formation of a core-shell fiber using double-co-axial laminar flow microfluidic device | F | N | Various | [190] |
| Fabrication of tubular channels resembling natural vessels | Bovine cartilage progenitor cells | Alginate | New co-axial system by pressure-assisted robotic bioprinting | P | N | Blood vessel | [292] |
| Developing bioprinting system for cell-laden hollow fibers | Bovine cartilage progenitor cells | Alginate | Manufacturing tubular microchannels by a pressure-assisted robotic system with co-axial nozzle | P | N | Not specific | [131] |
| Production of cell-laden vessel-like fibers and vascular network | Bovine cartilage progenitor cells | Alginate and chitosan | Co-axial bioprinting of microfibers and embedding in bulk hydrogel | P | N | Not specific | [132] |
| Developing a multi-arm bioprinter for hybrid formation of cell-laden 3D constructs | Cartilage progenitor cells | Alginate | Co-axial system (alginate core and CaCl2 sheath) | P | N | Not specific | [185] |
| Fabrication of reinforced vascular conduits | Human coronary artery smooth muscle cells | Alginate reinforced with carbon nanotubes (CNTs) | Co-axial bioprinting (sodium alginate as sheath and crosslinker in the core) | P | N | Not specific | [293] |
| Development of cell-encapsulated 3D hydrogel constructs | Human embryonic kidney (HEK-293) cells | Alginate | Co-axial bioprinting integrated with declogging mechanism | P | N/A (glass capillaries) | Not specific | [83] |
| ECM-alginate microfibers produced by microfluidics | sarcoma osteogenic osteoblast-like cells (SaOS-2) | Alginate with gelatin or particulate ECM | Microfluidic chip with the outlet tube immersed in a gelling solution | F | C | Bone | [181] |
| Development of 3D constructs of cell-laden alginate microfibers | Fibroblasts (NIH/3T3 cells) | Alginate | Microfluidic chip for printing on a magnetic substrate (magnet-driven assembly) | P | C | Not specific | [294] |
| Development of 3D constructs of hollow cell-laden calcium alginate microfibers | L929 mouse fibroblasts | Calcium alginate | Co-axial bioprinting with motorized Z stage | P | N | Not specific | [133] |
| Developing a novel microfluidic dispenser for integrating with inkjet bioprinters (Lab-on-a-Printer technology) | N/A | Alginate and collagen | PDMS microfluidic passive mixer directly integrated with PDMS/SU8 inkjet dispenser | P | C | Liver | [18] |
| Fabrication of branched hollow fibers | Mouse fibroblasts | Alginate | Triaxial extrusion | P | N | Blood vessel | [295] |
| Developing a novel 3D printing system with redesigned printhead for fabrication of 3D vascularized tissue | E Coli; Human umbilical vein endothelial cells (HUVECs) | Alginate | Co-axial extrusion; CaCl2 (inner needle) surrounded by alginate (extruded into CaCl2 bath) | P | N&C | Blood vessel | [187] |
| High-resolution bioprinting of cell-laden 3D constructs using low viscose cell-encapsulated alginate as bioink | Human umbilical vein endothelial cells (HUVECs); Primary rat cardiomyocytes (CMs) | Alginate and gelatin methacryloyl (GelMA) | Co-axial extrusion; alginate-GelMA bioink through internal needle and CaCl2 through external needle followed by two-step crosslinking | P | N&C | 3D cardiac tissue, etc. | [111] |
| Bioprinting 3D endothelialized scaffolds for manufacturing aligned myocardium | Human umbilical vein endothelial cells (HUVECs); primary rat neonatal cardiomyocytes (CMs); human induced pluripotent stem cells (hiPSCs) | Mixture of alginate, gelatin methacryloyl (GelMA), and photoinitiator (Irgacure 2959) | Co-axial bioprinting of endothelialized scaffolds, seeding with cardiomyocytes and housing in the designed perfusion bioreactor | P | N | Endothelialized myocardium | [107] |
| Bioprinting of perfusable vessel-like tubular constructs | Human umbilical vein endothelial cells (HUVECs); human mesenchymal stem cells (hMSCs) | Blend bioink of gelatin methacryloyl (GelMA), alginate and polyethylene glycol-tetra-acrylate (PEGTA) | Single step multilayered co-axial extrusion | P | N | Not specific | [86] |
| Development of porous 3D constructs made from calcium alginate microfibers | N/A | Calcium alginate | Capillary co-axial microfluidic bioprinting on a vacuum substrate | P | N | Not specific | [81] |
| Development of 3D constructs made from unidirectionally aligned cell-laden hydrogel fibers | Muscle cell precursors (C2C12); fibroblasts (BALB/3T3) | Alginate and semi-synthetic biopolymer (PEG-fibrinogen) | Custom-built bioprinter with co-axial extrusion system and programmable microfluidic pumps | P | N | muscle tissue | [106] |
| Developing moduar bioinks of single cell microgels blended with prepolymers for microextrusion bioprinting of 3D constructs | Mesenchymal stem cells (MSCs); bovine chondrocytes; endothelial cells (ECs) | Polyethylene glycol diacrylate (PEGDA) for microgels, then blended with various materials | Microfluidic flow focusing device to emulsify cell-laden prehydrogel in oil phase and produce single-cell-laden microgels which were then incorporated into various materials to produce macroconstructs using various fabrication methods | P | N&C | Not specific | [186] |
| Development of continues cell-laden hydrogel microfibers in various shapes (solid and hollow) and also 3D constructs by automated assembly | Human umbilical vein endothelial cells (HUVECs); MG63 cells | RGD (Arg-Gly-Asp)-modified alginate | continues extrusion in various shapes by microfluidic chip | P | C | Not specific | [210] |
| Development of vascularized 3D cell-laden constructs | Human umbilical vein endothelial cells (HUVECs) | Gelatin methacryloyl (GelMA) blended with alginate | Co-axial bioprinting followed by photocrosslinking, | P | N | Not specific | [197] |
| Development of 3D multicellular vascular constructs with multilevel fluidic channels | Mouse fibroblasts (L929); mouse smooth muscle cells (MOVAS); Human umbilical vein endothelial cells (HUVECs) | Alginate | Co-axial bioprinting of hydrogels encapsulated with different cell types through two separate co-axial nozzles | P | N | Functional vessels | [88] |
| Development of 3D cell-laden constructs with tuneable microenvironment | Various cells (HUVECs, MDA-MB-231, MCF7 breast cancer cells, and NIH/3T3 mouse fibroblasts) | Cell-laden gelatin methacryloyl (GelMA) in the core and alginate as sheath | Co-axial bioprinting of core/sheath microfibers followed by photocrosslinking | P | N | Not specific | [296] |
| Development of full-thickness chondral scaffolds with cell and material gradients | Human mesenchymal stem cells (hMSCs) and human articular chondrocytes (hACs) | gelatin methacryloyl (GelMA), methacrylated hyaluronic acid (HAMA), chondroitin sulphate (CS)- 2-aminoethyl methacrylate (AEMA) and Alginate | Microfluidic bioprinting coupled with co-axial extrusion | P | N&C | Cartilage tissue | [172] |