pH responsive cationic guar gum-borate self-healing hydrogels for muco-adhesion

Abstract

We developed a new muco-adhesive hydrogel composed of cationic guar gum (CGG) and boric acid (BA). The CGG-BA precursor solution of 0.5-2% w/v concentration exhibited fluidity at low pH (3-5), while gelation occurred within 1 min at physiological pH (7-8) conditions. Scanning electron microscopy and Fourier-transform infrared spectroscopy results confirmed the change in physical and chemical behavior, respectively, with change in pH. The pH-responsive self-healing ability was analyzed through microscopy and rheology. CGG-BA hydrogels showed good self-healing property at pH 7.4. The in vitro biocompatibility test of the hydrogel studied using NIH3T3 and NHEK cells showed that it was non-toxic at concentrations of CGG-BA below 2% w/v. Ex vivo mucoadhesive tests confirmed the hydrogel's potential for use as a muco-adhesive. Burst pressure tests were conducted using pig esophageal mucosa and the results showed that at pH 7.4, 1% w/v CGG-BA self-healable hydrogel resisted about 8 ± 2 kPa pressure, comparable to that of Fibrin glue. This was higher than that at solution (pH 5) and brittle gel (pH 10) conditions. To confirm the good adhesive strength of the self-healable hydrogels, lap shear tests conducted, resulted in adhesive strengths measured in the range of 1.0 ± 0.5-2.0 ± 0.6 kPa, which was also comparable to fibrin glue control 1.8 ± 0.6 kPa. Hydrogel weight measurements showed that 40-80% gel lasted under physiological conditions for 10 h. The results suggest that CGG-BA hydrogel has potential as a pH responsive mucosal protectant biomaterial.

Keywords: Self-healing; hydrogels; muco-adhesion.

Graphical abstract

Figure 1.

(a) Crosslinking reaction between CGG and BA, (b) Expected muco-adhesive potential of CGG-BA hydrogel.

Figure 2.

(a) Schematic of the burst pressure measurement, (b) Image of the experimental setup.

Figure 3.

Effect of pH (5, 6, 7, 7.4, 8, 10) on CGG-BA mixtures. (a) Images of CGG-BA mixtures, (b) Gelation time of CGG-BA mixtures, (c) Frequency sweep of CGG-BA mixtures.

Figure 4.

SEM images (resolution 500μm) of CGG-BA with different pH.

Figure 5.

FTIR spectra of CGG-BA with pH = 5, 7.4, and 10. Arrows indicate the characteristic peaks.

Figure 6.

Effect of pH on yield stress and tackiness of CGG-BA hydrogels. (a) G′ and G″ as a function of shear stress on the hydrogel, (b) τ_y of hydrogels at different pH. (c) Normal force exerted on the hydrogel during the tack measurement as a function of time, (d) the tackiness force (F_max) and work of adhesion (W_adh) of hydrogels at different pH.

Figure 7.

Self-healing behavior of CGG-BA at different pH. (a) Images of 1% CGG-BA when two cut pieces of hydrogel with pH 7.4 and pH 10 were brought in contact. Scale: 1 cm, (b) Rheological evaluation of restructuring of 2% w/v hydrogels at pH 5, 7.4, and 10 by subjecting to alternate low (1%) and high (1000%) strains.

Figure 8.

Cell viability test of CGG-BA hydrogels against NIH3T3 and NHEK cells.

Figure 9.

Results of ex vivo mucoadhesive test (a) Increase in resistance pressure with time on ejection of PBS through hydrogel attached to porcine esophageal mucosa, (b) Burst pressure of CGG-BA hydrogels at pH 5, 7.4 and 10, and that of fibrin glue control, (c) Adhesive strength of hydrogels calculated by lap shear measurement, (d) Degradation behavior of hydrogels applied on the mucosa during the incubation in PBS. (N. S. (non-significant), P < 0.05, P < 0.01 and P < 0.001 refers to the statistical significance).