Metre-long cell-laden microfibres exhibit tissue morphologies and functions

Abstract

Artificial reconstruction of fibre-shaped cellular constructs could greatly contribute to tissue assembly in vitro. Here we show that, by using a microfluidic device with double-coaxial laminar flow, metre-long core-shell hydrogel microfibres encapsulating ECM proteins and differentiated cells or somatic stem cells can be fabricated, and that the microfibres reconstitute intrinsic morphologies and functions of living tissues. We also show that these functional fibres can be assembled, by weaving and reeling, into macroscopic cellular structures with various spatial patterns. Moreover, fibres encapsulating primary pancreatic islet cells and transplanted through a microcatheter into the subrenal capsular space of diabetic mice normalized blood glucose concentrations for about two weeks. These microfibres may find use as templates for the reconstruction of fibre-shaped functional tissues that mimic muscle fibres, blood vessels or nerve networks in vivo.

Fabrication of tough poly(ethylene glycol)/collagen double network hydrogels for tissue engineering

“…[4][5][6][7] Moreover, hydrogels that are based on biomolecules, 8 such as proteins (e.g., collagen [Col] 9 and gelatin 10,11 ) and polysaccharides (e.g., hyaluronic acid 12,13 and chitosan 14,15 ), acquire not only excellent biocompatibility but also specific bioactivity from their building blocks. These features can artificially mimic the extracellular matrix (ECM) for cell growth and proliferation, 16 and are highly advantageous in tissue regenerative therapy.…”

Biomimicry, Biofabrication, and Biohybrid Systems: The Emergence and Evolution of Biological Design

“…[47] These types of biological microfibers can be assembled into higher-order structures using microfluidic weaving apparatus, as demonstrated by Takeuchi and co-workers. [48] Several promising manufacturing approaches for seeding cell-laden hydrogels with and within microfluidic systems have been developed. Depending on the application at hand, a combination of these approaches can be used to study interactions between multiple cell or tissue types, and reconstitute the complexity of in vivo architecture and microenvironment.…”

“…By testing tissue fibers in vivo, they have also been able to demonstrate the safety and feasibility of this approach for medical applications in the future. [48] Recently, Tate and co-workers have proposed an algorithm for weaving biological tissues by mapping the composition and 3D distribution of collagen and elastin fibers in bone and inputting the information into a digital loom. [69] This approach could, by mimicking the 3D micro-to macroscale architecture seen in nature, help replicate the strength, resilience, and lightness of biological systems.…”

Versatile, cell and chip friendly method to gel alginate in microfluidic devices

“…11 In particular, the selectivity of sequences of guluronic acid residues to interact with Ca 2+ and induce gelation 12 under mild, physiologically compatible conditions, are widely explored. Use of alginate has for instance been demonstrated for encapsulation of cells for tissue engineering purposes [13][14][15][16] and has been investigated for treatment of diabetes mellitus type I. 17,18 However, a number of technical barriers currently remain which limit the applicability of the Ca 2+ induced gelation in microfluidics, including.…”