A hybrid approach to full-scale reconstruction of renal arterial network.

The renal vasculature, acting as a resource distribution network, plays an important role in both the physiology and pathophysiology of the kidney. However, no imaging techniques allow an assessment of the structure and function of the renal vasculature due to limited spatial and temporal resolution. To develop realistic computer simulations of renal function, and to develop new image-based diagnostic methods based on artificial intelligence, it is necessary to have a realistic full-scale model of the renal vasculature. We propose a hybrid framework to build subject-specific models of the renal vascular network by using semi-automated segmentation of large arteries and estimation of cortex area from a micro-CT scan as a starting point, and by adopting the Global Constructive Optimization algorithm for generating smaller vessels. Our results show a close agreement between the reconstructed vasculature and existing anatomical data obtained from a rat kidney with respect to morphometric and hemodynamic parameters.

Composable microfluidic spinning platforms for facile production of biomimetic perfusable hydrogel microtubes.

Microtissues with specific structures and integrated vessels play a key role in maintaining organ functions. To recapitulate the in vivo environment for tissue engineering and organ-on-a-chip purposes, it is essential to develop perfusable biomimetic microscaffolds. We developed facile all-aqueous microfluidic approaches for producing perfusable hydrogel microtubes with diverse biomimetic sizes and shapes. Here, we provide a detailed protocol describing the construction of the microtube spinning platforms, the assembly of microfluidic devices, and the fabrication and characterization of various perfusable hydrogel microtubes. The hydrogel microtubes can be continuously generated from microfluidic devices due to the crosslinking of alginate by calcium in the coaxial flows and collecting bath. Owing to the mild all-aqueous spinning process, cells can be loaded into the alginate prepolymer for microtube spinning, which enables the direct production of cell-laden hydrogel microtubes. By manipulating the fluid dynamics at the microscale, the composable microfluidic devices and platforms can be used for the facile generation of six types of biomimetic perfusable microtubes. The microfluidic platforms and devices can be set up within 3 h from commonly available and inexpensive materials. After 10-20 min required to adjust the platform and fluids, perfusable hydrogel microtubes can be generated continuously. We describe how to characterize the microtubes using scanning electron or confocal microscopy. As an example application, we describe how the microtubes can be used for the preparation of a vascular lumen and how to perform barrier permeability tests of the vascular lumen.

Correction: Hydrogel microfibers with perfusable folded channels for tissue constructs with folded morphology.

[This corrects the article DOI: 10.1039/C8RA04192J.].

Necklace-Like Microfibers with Variable Knots and Perfusable Channels Fabricated by an Oil-Free Microfluidic Spinning Process.

Fiber materials with different structural features, which in many cases endow the fibers extraordinary functions, are drawing considerable attention from biomedical and material researchers. Here, perfusable necklace-like knotted microfibers are presented for the first time. Additionally, a novel microfluidic spinning method facilitates the production of variable knots and channels. Not only spindle-, but also hemisphere- and petal-knotted microfibers can be controllably fabricated. Generation and perfusion of both Janus channels and helical channel in the knotted microfibers are also shown. With no need of oil and surfactant, the spinning process is highly cytocompatible. The potential bioengineering and biomedical application of the knotted hollow microfiber is demonstrated by its cell-encapsulation feasibility and the unique liver acinus-like diffusion gradient in the knot. The merits of perfusability, cytocompatibility, and structural diversity of the microfibers may open more avenues for further material and biomedical investigation.

Hydrogel microfibers with perfusable folded channels for tissue constructs with folded morphology.

Fiber-based materials with microchannels have drawn considerable attention in recent years owing to their ability to mimic intrinsic morphologies of living tissues. Folded morphologies, which are common in vivo, such as in skeletal muscle capillaries and intestine luminal endoderm, play important roles in the achievement of tissue functions. Here, microfibers with folded hollow channels are fabricated. Channel morphologies, such as straight-folded, double-folded and double-helical channels, can be regulated by adjusting flow conditions in the microfluidic devices. To further demonstrate the potential to be used in tissue engineering, intestine and skeletal muscle constructs are fabricated using these microfibers as building blocks. Furthermore, the properties of perfusability, permeability, cytocompatibility and weavability of the microfibers are evaluated. The asymmetric molecular distributions in the microfibers provide promising platforms for the study of nutrient exchange and energy supplement between normal and tortuous tissues. The new features of biofibers and proof-of-concept of tissue constructs with folded morphologies may contribute to the development of regenerative medicine and drug screening in the future.

Bioinspired Microfibers with Embedded Perfusable Helical Channels.

Materials with microchannels have attracted increasing attention due to their promising perfusability and biomimetic geometry. However, the fabrication of microfibers with more geometrically complex channels in the micro- or nanoscale remains a big challenge. Here, a novel method for generating scalable microfibers with consecutive embedded helical channels is presented using an easily made coaxial microfluidic device. The characteristics of the helical channel can be accurately controlled by simply adjusting the flow rate ratio of the fluids. The mechanism of the helix formation process is theorized with newly proposed heterogenerated rope-coil effect, which enhances the tunability of helical patterns and promotes the comprehension of this abnormal phenomenon. Based on this effect, microfibers with embedded Janus channels and even double helical channels are generated in situ by changing the design of the device. The uniqueness and potential applications of these tubular microfibers are also demonstrated by biomimetic supercoiling structures as well as the perfusable and permeable spiral vessel.

Double-Network Hydrogel with Tunable Mechanical Performance and Biocompatibility for the Fabrication of Stem Cells-Encapsulated Fibers and 3D Assemble.

Fabrication of cell-encapsulated fibers could greatly contribute to tissue engineering and regenerative medicine. However, existing methods suffered from not only unavoidability of cell damaging conditions and/or sophisticated equipment, but also unavailability of proper materials to satisfy both mechanical and biological expectations. In this work, a simple method is proposed to prepare cell-encapsulated fibers with tunable mechanical strength and stretching behavior as well as diameter and microstructure. The hydrogel fibers are made from optimal combination of alginate and poly(N-iso-propylacrylamide)-poly(ethylene glycol), characteristics of double-network hydrogel, with enough stiffness and flexibility to create a variety of three dimensional structures like parallel helical and different knots without crack. Furthermore, such hydrogel fibers exhibit better compatibility as indicated by the viability, proliferation and expression of pluripotency markers of embryonic stem cells encapsulated after 4-day culture. The double-network hydrogel possesses specific quick responses to either of alginate lyase, EDTA or lower environmental temperature which facilitate the optional degradation of fibers or fibrous assemblies to release the cells encapsulated for subsequent assay or treatment.