Strong, antioxidant, and biodegradable gelatin methacryloyl composite hydrogel for oxidative stress protection in Schwann cells

Abstract

Gelatin methacryloyl (GelMA), a biomaterial widely used in tissue engineering, exhibits excellent biocompatibility and cell adhesion properties. However, its poor mechanical strength and functional monotony restrict broader clinical applications of this material. In this study, we introduced sodium acrylate (SA) and tannic acid (TA) into the GelMA system via a two-step crosslinking strategy, successfully fabricating a GelMA/SA-TA (GST) composite hydrogel that achieved dual enhancement of mechanical and antioxidant properties. The incorporation of SA and TA significantly improved the mechanical performance of the hydrogel, which exhibited a maximum tensile modulus of 31.83 ± 2.84 kPa. At the same time, TA endowed the hydrogel with exceptional antioxidant ability, resulting in a free radical scavenging rate of 89.93% ± 0.9% in vitro. Biological tests revealed that the GST hydrogel effectively alleviated oxidative stress damage in rat Schwann cells (RSC96) by suppressing the generation of reactive oxygen species (ROS) and promoting the secretion of brain-derived neurotrophic factor (BDNF). This work presents the first report of an antioxidant hydrogel capable of protecting Schwann cells without compromising their mechanical integrity, highlighting its transformative potential for peripheral nerve injury repair. The synergistic SA-TA modification strategy provides new insights into the design of multifunctional biomaterials for neural regeneration applications.

Keywords: Schwann cell; antioxidant; gelatin methacryloyl; peripheral nerve injury; tannic acid.

FIGURE 1

Schematic illustration of GST hydrogel synthesis and its functional effects on Schwann cells.

FIGURE 2

(a) FT-IR spectra of individual component materials and composite hydrogels; (b) SEM images of hydrogels (scale bar = 500 μm).

FIGURE 3

(a) Swelling ratios of hydrogels at 72 h; (b) time-dependent swelling behavior of hydrogels; (c) water content of hydrogels; (d) degradation profiles of hydrogels. ***p < 0.001.

FIGURE 4

(a) Compression tests; (b) tensile tests; (c) compressive moduli; (d) tensile moduli. *P < 0.05, **P < 0.01, ***P < 0.001; ns indicates not statistically significant differences.

FIGURE 5

(a) TA absorption efficiencies; (b) TA release profiles; (c) DPPH radical scavenging rates; (d) representative images of DPPH assay. *P < 0.05, ***P < 0.001.

FIGURE 6

(a) OD values from CCK-8 assays of RSC96 cells cultured in different hydrogel extracts for 1, 3, and 5 days; (b) live/dead staining of RSC96 cells after 5 days of culture. Green and red colors indicate live and dead cells, respectively (scale bar = 100 μm). **P < 0.01, ***P < 0.001; ns denotes not statistically significant differences.

FIGURE 7

(a) OD values of RSC96 cells under H₂O₂ induction across different experimental groups; (b) quantitative analysis of cell migration rates; (c) scratch wound healing assays of control, H₂O₂, H₂O₂ + GS, and H₂O₂ + GST groups (scale bar ; 200 μm); (d) ROS staining of cells in each group using DCFH-DA probe; (e) quantitative analysis of fluorescence intensity (scale bar ; 100 μm); (f) relative BDNF expression levels in control, H₂O₂, H₂O₂ + GS, and H₂O₂ + GST groups. **P < 0.01, ***P < 0.001; ns indicates not statistically significant differences.