Table 5.

Comparison of different synthetic strategies of 3D matrix-based.

Fabrication Method	Method Overview	Scaffolding Morphology	Advantages	Disadvantages
Hydrogels [11,54,193,279,280,281]	-Collagen gel solution (usually type 1 collagen and acetic acid) mixed on ice and usually neutralized (NaOH) and then gelled -Physical parameters: collagen, pH, the temperature of desired gelling	-Dense gel network of string-like fibers. The thickness of the fiber depends on the manufacturing parameters	-Easy to apply -Matrigel is widely used in cancer research, so many user guides are available -High level of cell viability	-The least porous -Risk of poor distribution of cells and nutrients. -An architecture is more difficult to control, therefore, has less reproducibility of the exact architectures desired -Poor mechanical properties before cross-linking
Lyophilization [153,276,292,293,294,295,296,297,298]	-Creation of a homogeneous suspension of collagen with acid (usually acetic acid) at high speed -Heat treatment (controlled or quenched) for the sublimation of ice crystals under vacuum to the defined freezing point before returning to ~0 °C The dried scaffolding must reach room temperature to complete the process	-Interconnected network -Highly porous -A well-defined pore shape and sizes	-Good control of scaffolding architecture -A wide production range in terms of pore sizes and orientation -High porosity levels. -Inexpensive-High level of cell viability	-Problems in the freezing process affect the final scaffolding architecture from one batch to another -Poor mechanical properties before cross-linking
Electrospiding [299,300,301,302,303,304,305,306,307,308,309,310,311,312]	-Collagen solubilized (usually HFIP or TFE) and added to the syringe/injection system -A high-voltage electric field is applied, causing the charge of the solution, the eruption of the polymer fiber of the tip of the needle, and the whip of the liquid jet -The solvent evaporates during the process, leaving a network of dried fibers deposited on the collection plate (non-woven or aligned)	-Dense and tight fiber array (chain-shaped) of nanometric or micro size	-Fibrous network that closely resembles native collagen fibers. -Wide range of size/diameter/achievable fiber pattern -High level of reported cell viability	-Use of harmful solvents (collagen scaffolding) -Solvents are expensive -Dense fiber networks can reduce the level of cellular infiltration.
Stereolithography [277,313,314,315,316,317,318,319]	-prints layer by layer a UV-curable material in thin sheets -Installation of a multiresolution 3D printer (Dilase 3D, Kloe France) -Each layer is superimposed after drying the next layer -Use of different light sources (visible, UV, IR) capable of polymerizing photosensitive materials.	-Hard layer set (UV)	-Capable of producing scaffolding of size mm to cm -Can be combined with different components to hydrogels or electro spinning (PCL fibers, PCL /gelatin) -high differentiation rates and adhesion -Imitates complex structures in vitro: as villi of the intestine	-Specific equipment -Expensive -Manufactured scaffolding is usually limited to a few tens of microns of resolution
Micro fluid [278,320,321,322,323,324,325,326,327,328,329,330,331,332,333]	Support consisting of silicon/elastomer-based devices having microchannels with proportions from 1 to 1000 μm that exploit a small volume of fluids (10-9 to 10-18 L). These fluids are continuous flows of nutrients and therapeutic agents, establish a physiological profile such as that of blood circulation and intravenous injections	-Matrix that has micro channels- which can be either strictly laminar (in parallel layers) or turbulent (parallel and strong numbers)	-Labor-saving -Microenvironment dynamics (fluid flow) -Generate aggregates of different forms Co-culture of several cells -Simulates cell-cell contacts and biological signals controlled by spatial and temporal gradients of soluble biological factors -Study tumor progression, invasion, angiogenesis as well as treatment tests -Low reagent consumption and low cell utilization	-Requiring professional equipment and special design -Complexity. -High cost