Hybrid Vesicles Enable Mechano-Responsive Hydrogel Degradation

Abstract

Stimuli-responsive hydrogels are intriguing biomimetic materials. Previous efforts to develop mechano-responsive hydrogels have mostly relied on chemical modifications of the hydrogel structures. Here, we present a simple, generalizable strategy that confers mechano-responsive behavior on hydrogels. Our approach involves embedding hybrid vesicles, composed of phospholipids and amphiphilic block copolymers, within the hydrogel matrix to act as signal transducers. Under mechanical stress, these vesicles undergo deformation and rupture, releasing encapsulated compounds that can control the hydrogel network. To demonstrate this concept, we embedded vesicles containing ethylene glycol tetraacetic acid (EGTA), a calcium chelator, into a calcium-crosslinked alginate hydrogel. When compressed, the released EGTA sequesters calcium ions and degrades the hydrogel. This study provides a novel method for engineering mechano-responsive hydrogels that may be useful in various biomedical applications.

Keywords: Block Copolymers; Functional Material; Stimuli-Responsive Hydrogel; Stress-Induced Degradation; Vesicles.

Figure 1.

(A) Schematic of preparation of a mechano-responsive degradable hydrogel. The vesicles containing EGTA, a calcium chelator, were incorporated into alginate macromer solution, and calcium ions were added to crosslink the hydrogel. Application of compressive stress to the hydrogel leads to the release of EGTA from the vesicles, resulting in the degradation of the hydrogel. (B) Schematic of generation of vesicles using the continuous droplet interface crossing encapsulation (cDICE) method. Water-in-oil droplets pass through an oil-water interface to form a complete bilayer structure. Note that the schematics are not drawn to scale.

Figure 2.

(A) Brightfield and fluorescence images of the embedded vesicles and fluorescent beads within the hydrogel. (B) Monitoring of fluorescent dye (Cy-5)- in the same vesicle embedded in the hydrogel for 30 days. Consistent bead positions (white arrows) demonstrate the vesicle is maintaining its position within the hydrogel matrix. (C) Schematic illustration of the hydrogel compression setup. (D) Photographs of the hydrogels before and after application of external force using the setup in (C).

Figure 3.

Characterization of hydrogel degradation through Brownian motion analysis of fluorescent beads in compressed and uncompressed hydrogels. (A) Representative examples demonstrating the Brownian motion of the fluorescent beads. (B) Diffusion coefficient of the fluorescent beads (n = 15). Statistical significance was determined using a two-tailed Student’s t-test: n.s. (not significant); *** p < 0.001.

Figure 4.

Characterization of hydrogel degradation through residual hydrogel weight measurement after compression. (A) Illustration showing the process used to measure the weight of the residual hydrogel. (B) Comparison of the normalized hydrogel weight from different conditions with and without applied stress (55 kPa). Statistical significance was determined by ANOVA: n.s. (not significant); *** p < 0.001. (C) Photographs showing the residual hydrogels on the membrane filter after stress application (55 kPa). (D) Normalized weight of hydrogels containing EGTA-loaded vesicles under different stress conditions (0, 33, 55 kPa). Error bars represent standard deviations (n = 3–5).

Figure 5.

Mechanical characterization of the hydrogel conditions (without vesicles, vesicles without EGTA, vesicles with EGTA) with and without the stress application (55 kPa) for 20 minutes. Statistical significance was determined by ANOVA: n.s. (not significant); * p < 0.05; ** p < 0.01. Error bars represent standard deviations (n = 3).