## 4 Discussion
These considerations are true for the vascular patterns of both intestine and mesentery (here treated distinctly, because of their different vascular organization and functions [32]). A reason for the departure of the printed patterns from the initial images is also due to a technical limitation related to the current status of the printing technology. On some instruments (including ours) the straight or other geometric lines can be printed continuously with a resolution close to the diameter of the printheads (which in extrusion mode can be 0.25 mm or less). However, an arbitrarily shaped, tortuous line is treated by the path-generation software as a very elongated 'object', which is then further decomposed in shorter, parallel segments. This rendering generates thicker lines than the original ones, even when printed in a single layer. Added to this complication are the printability and hardening of the hydrogel (with or without a crosslinker), as well as its adhesivity to the substrate which, when too high, will lead to additional widening of the lines. However, all these artifacts may have a lesser impact on the thickness of the actual cell cords generated within the printed hydrogel patterns. In fact, the ultimate arbiters of cells organization in cords are: (i) their phenotypes and composition (e.g., if adding or not supporting pericytes), (ii) the dynamics of self-assembling, and (iii) the in situ maturation process. Moreover, in vivo, these vasculogenic processes will be further sculptured by the contribution of inflammatory and/or repairing cells, mainly by the macrophages' M1/M2 ratio, and possibly by spontaneously recruited progenitor cells [33], or by intentionally adding iPSC-derived vascular cells [34]. An alternative method to generate microvascular conduits in vitro relies on microfluidic devices containing microvascular channels, which demonstrate great benefits for in vitro experimentation for mechanistic studies and drug discovery [35]. Among their advantages are: design is straightforward to implement; conveniently grouped as either linear (or geometrically-branched) channels directly lined by endothelial cells, or hydrogel microdomains spontaneously colonized with microvascular cells (endothelial, smooth muscle cells and/or pericytes) by sprouting or self-assembly; controllable placement as related to their surroundings; predictable and stable conduit diameters; easy to connect to the outside fluid supply and to perfuse; ability to integrate with multiple parenchymal cell types, generating single or interconnected 'organs on chip' [36]; in-plane confinement for high quality microscopic imaging, etc. These possibilities are derived from embedding the microfluidic channels in plastic material supports with pre-designed spatial features implemented by photolithography. However, from the standpoint of vascularization this technology has the following limitations: it may be constrained to the use of only pre-determined cell types capable to initially adhere to the walls of the microchannels; the presence of plastic materials could interfere with the inter-cellular interactions of the microvascular and parenchymal cells; due to the presence of plastics, it is not suitable for in vivo implantation; the active areas are limited to small ('chip') size ranges; further assembly is possible only by stacking and/or inter-device coupling, and this cannot generate natural 3D shapes; the devices have a predetermined, rigid spatial distribution, limiting the cells' ability to self-organize only to the hydrogel microdomains and spontaneously adopt co-localization optimal for their function; the shapes of the microfluidic channels were in general linear or with simple geometric branches, constrained by the need of maintain a laminar flow inside of them, while in principle being possible to design more physiologic designs, etc.