Creating polymer hydrogel microfibres with internal alignment via electrical and mechanical stretching

Abstract

Hydrogels have been widely used for 3-dimensional (3D) cell culture and tissue regeneration due to their tunable biochemical and physicochemical properties as well as their high water content, which resembles the aqueous microenvironment of the natural extracellular matrix. While many properties of natural hydrogel matrices are modifiable, their intrinsic isotropic structure limits the control over cellular organization, which is critical to restore tissue function. Here we report a generic approach to incorporate alignment topography inside the hydrogel matrix using a combination of electrical and mechanical stretching. Hydrogel fibres with uniaxial alignment were prepared from aqueous solutions of natural polymers such as alginate, fibrin, gelatin, and hyaluronic acid under ambient conditions. The unique internal alignment feature drastically enhances the mechanical properties of the hydrogel microfibres. Furthermore, the facile, organic solvent-free processing conditions are amenable to the incorporation of live cells within the hydrogel fibre or on the fibre surface; both approaches effectively induce cellular alignment. This work demonstrates a versatile and scalable strategy to create aligned hydrogel microfibres from various natural polymers.

Regenerative and durable small-diameter graft as an arterial conduit

“…Preparation of Fibrin Hydrogel Microfiber Tubes and PCL Sheaths. Fibrin hydrogel microfiber sheets were prepared by electrospinning 2.0 wt % fibrinogen codissolved in 0.2 wt % polyethylene oxide onto a grounded, rotating collection bath containing 50 mM calcium chloride and 20 U/mL thrombin as previously described (41)(42)(43). The landing position of the spinning jet was ENGINEERING APPLIED BIOLOGICAL SCIENCES rastered back and forth to yield a uniform aligned fibrin sheet, which was rolled onto a PTFE-coated mandrel.…”

The stiffness of a crosslinked hyaluronan hydrogel affects its chondro‐induction activity on hADSCs

“…This mutually dependent relationship between cells and their surrounding environment is a symbiotic interaction, wherein cells can remodel their surrounding matrix; moreover, the mechanical, structural and chemical compositions of these surroundings regulate intracellular processes . Several studies focused on general cell behaviors, such as cell attachment, orientation, migration or proliferation, which are affected by hydrogel stiffness . Here, the physical properties of the crosslinked MeHA hydrogels were controlled by modulating the degree of methacrylation using a standardized hydrogel synthesis process (macromer concentration, molecular weight, and duration of UV exposure); the hydrogels subsequently induced the stiffness‐dependent chondrogenic differentiation of hADSCs.…”

“…24 Several studies focused on general cell behaviors, such as cell attachment, orientation, migration or proliferation, which are affected by hydrogel stiffness. [25][26][27][28] Here, the physical properties of the crosslinked MeHA hydrogels were controlled by modulating the degree of methacrylation using a standardized hydrogel synthesis process (macromer concentration, molecular weight, and duration of UV exposure); the hydrogels subsequently induced the stiffness-dependent chondrogenic differentiation of hADSCs. Although methacrylation is a commonly used method for modifying HA hydrogel synthesis, the ability to control the precise degree of methacrylation has often been underestimated.…”

Fabrication of 3-dimensional multicellular microvascular structures

“…We previously established a modified electrospinning technique whereas different biomaterials were spun, collected in an aqueous phase, bundled together, and mechanically stretched to make hydrogel microfibers with an internal and external alignment. We demonstrated that the mild process conditions allowed the encapsulation of cells within the microfibers, as well as seeding of cells postspinning on top of them (15). We then utilized fibrin microfibers fabricated with this technique to guide the organized formation of a confluent and aligned EC monolayer with a cylindric 3D shape and marked expression of EC markers CD31, VEcad, and von Willebrand factor (16).…”

“…Recently, we introduced a modified electrospinning technique that allowed us to fabricate hydrogel microfibers with an internal and external alignment and with tunable diameters between tens and hundreds of micrometers (15). Fibrin microfibers created with this technique support endothelial colony‐forming cell (ECFC) growth, alignment, and deposition of basal lamina proteins Col IV, Fn, and Lmn.…”