Electric field-driven building blocks for introducing multiple gradients to hydrogels

Abstract

Gradient biomaterials are considered as preferable matrices for tissue engineering due to better simulation of native tissues. The introduction of gradient cues usually needs special equipment and complex process but is only effective to limited biomaterials. Incorporation of multiple gradients in the hydrogels remains challenges. Here, betasheet rich silk nanofibers (BSNF) were used as building blocks to introduce multiple gradients into different hydrogel systems through the joint action of crosslinking and electric field. The blocks migrated to the anode along the electric field and gradually stagnated due to the solution-hydrogel transition of the systems, finally achieving gradient distribution of the blocks in the formed hydrogels. The gradient distribution of the blocks could be tuned easily through changing different factors such as solution viscosity, which resulted in highly tunable gradient of mechanical cues. The blocks were also aligned under the electric field, endowing orientation gradient simultaneously. Different cargos could be loaded on the blocks and form gradient cues through the same crosslinking-electric field strategy. The building blocks could be introduced to various hydrogels such as Gelatin and NIPAM, indicating the universality. Complex niches with multiple gradient cues could be achieved through the strategy. Silk-based hydrogels with suitable mechanical gradients were fabricated to control the osteogenesis and chondrogenesis. Chondrogenic-osteogenic gradient transition was obtained, which stimulated the ectopic osteochondral tissue regeneration in vivo. The versatility and highly controllability of the strategy as well as multifunction of the building blocks reveal the applicability in complex tissue engineering and various interfacial tissues.

Advances in the Fabrication of Biomaterials for Gradient Tissue Engineering

“…In this work, β-sheet rich silk nanofibers moved to the anode of an applied electric field, with the migration kinetics tuned to the gelation rate Peer reviewed version of the manuscript published in final form in Trends in Biotechnology (2020). of the surrounding polymer (GelMA, N-isopropylacrylamide or amorphous silk nanofiber solution) (Figure 3C) [70].…”

Advances in Engineering Human Tissue Models

“…In the case of MSCs, for instance, it has been shown that the RGD cell-adhesive motif is essential for stem cell survival at the early stages of 3D culture in PEG hydrogels, while removal of ligands at later stages does not compromise the viability of cells, but rather improves their differentiation (Kloxin et al, 2009 ). To overcome limitations in delivering natural cues in a spatiotemporal manner the development of dynamic biomaterials that allow for reversible modulation of the physicochemical properties and on-demand release of the desired molecules via either cell-mediated or user-mediated mechanisms, represents a promising strategy (Willerth et al, 2008 ; Leijten et al, 2017 ; Schneeberger et al, 2017 ; Cimmino et al, 2018 ; Kratochvil et al, 2019 ; Xu et al, 2020 ). A characteristic example where the delivery of physicochemical cues is mediated by cell activity is remodelable 3D hydrogels.…”

Silk-Based Materials for Hard Tissue Engineering

“…Between week 8 to 12, newly formed bone was found in the case of the stiffest hydrogel samples, whereas the aligned fiber structure also led to alignment in the new tissue. The fabrication method with two silk fibroin morphologies and electric field alignment was then used by the same group to fabricate gradient hydrogels [ 132 ]. In further detail, horseradish crosslinking times and resulting gradient mechanical properties were investigated.…”