scaffolds

/microfluidics

Native tissue contains macro-and micro-blood vessels that supply nutrients,oxygen,and other bio-molecules to large cell number of studies have investigated micropatterned substrates to create capillary bed-like structures that mimic native tissue as shown in factors,such as ECM stiffness,interstitial and shear flow have significant effects on capillary vessel formation in micropatterned particular,interstitial flow regulates capillary morphogenesis[45],shear stress enhances angiogenesis[46],and material stiffness regulates the architecture of the capillary network in the developing one study,bovine pulmonary microvascular ECs seeded in rigid collagen gels formed thick and deep vascular networks with large capillary lumens,while those seeded in a flexible hydrogel formed thin and intense networks with tiny lumen[47].Researchers have used plasma etching[48],laser ablation[49],soft lithography[50],and replica molding[51]to generate microfluidic patterns on biocompatible have also used a direct write laser technique to prepare microchannels with various widths and depths following Murray's law to closely mimic the capillary architecture seen in micropatterns facilitate the uniform flow of fluid and achieve low resistance similar to that of physiological vascular systems[52].

of scaffolds using a computer-controlled ultraviolet laser beam:(A)projection microstereolithography(SEM image at right is an octet-truss unit cell),(B–E)octet-truss structures with different patterns and biomaterials,and(F–I)SEM images of the struts of structures in(B–E)(reproduced with permission from[44]).

To date,several methods have been developed to seed vascular and tissue-specific cells on patterned one study,ECs and mural cells( muscle cells(SMCs)and pericytes)were seeded in a single-layered substrate following a microfluidic approach,and then cultured for a certain period of time to promote stable capillary formation[54].Several studies report that microfluidics regulate the temporal and spatial distribution of cells,media,enzymes,and biomolecules within the micropattern[55].Further,microfluidics facilitates the formation of patterned cell distribution and shear-induced endothelialization in a coculture system[56].Especially in a microfluidic system,circulating biomolecules and the applied gradient of shear stress into the microchannel regulate the morphology,reorganization,alignment,differentiation,and remodeling of ECs that are significant for capillary formation[57].To regulate shear stress,researchers have applied computational microfluidics and different fluid flow patterns(,pulsatile,and turbulent)that result in the formation of endothelial monolayers around the microchannels[58,59].Micropatterned single planar layer substrates prepared in this way are compiled to form macro 3D tissue the preparation and assembly of multiple layers is a time-consuming process,researchers have searched for alternative ways to fabricate 3D macro-sized substrates with microfluidic of advanced technologies,such as direct write assembly(robotic deposition,fused deposition,and two-photon polymerization)[60],sacrificial material-based extrusion printing[21],modular assembly[61],omnidirectional printing()[62],and electrostatic discharge printing(Figs.5G and H)[63]have demonstrated unprecedented success in generating complex 3D vascular complex patterns are often embedded in hydrogel-containing tissue-specific cells.

The success of microfluidics networks in terms of vasculature formation largely depends on the mechanical and biological properties of the wide range of synthetic polymers,including poly (methylmethacrylate), poly(dimethyl siloxane),silicon,polycarbonate,polyvinyl chloride,polystyrene,poly(lactic-co-glycolic)acid(PLGA),and poly(glycerol sebacate)have been used in microfluidics[64].However,EC monolayers grown into micropatterned synthetic substrates show poor barrier function in terms of transporting biomolecules,oxygen,and patterned synthetic materials show poor biodegradation,barrier function,and biocompatibility and provoke cytotoxicity and inflammatory responses in vivo,researchers have explored a wide range of hydrogels for printing micropatterns for vasculature number of studies have used silk fibroin,Matrigel,type I collagen,and fibrin to form endothelial tubes in 3D scaffolds[65].By nature,these hydrogels are biodegradable and biocompatible and can provide a 3D milieu for vascular network addition to the biomaterials,several parameters have been identified as potential factors in generating microvessels with example,the combined effect of microfluidics and vasculogenesis from cell seeding grew perfusable and functional microvessels in a 3D fibrin gel system in vitro and showed strong barrier function and long-term stability[66].Similarly,the collective effects of growth factors and fluid shear stress have also been investigated,with gradients of vascular endothelial growth factor(VEGF)and angiopoietin 1(ANG-1)forming a stable and c onnected 3D capillary network within a type-I collagen matrix embedded with microfluidic channels[67].The success of such a strategy led researchers to further explore the synergistic effect of multiple parameters to promote and regulate capillary formation in a 3D microfluidics-hydrogel of HUVECs and human lung fibroblasts(HLFs)in fibrin gels/microfluidics systems containing VEGF and sphingosine-1-phosphate(S1P)promoted the formation of a stable capillary network with smaller lumen diameters[68].In addition,stem cell-incorporated gels/microfluidic systems have been example,a co-culture of HUVECs and MSCs in a collagen gel/microfluidic system reduced capillary formation,but stabilized the newly formed capillaries[69].

文章来源：《现代制造技术与装备》 网址: http://www.xdzzjsyzb.cn/qikandaodu/2020/1028/666.html