Berberine-Incorporated Shape Memory Fiber Applied as a Novel Surgical Suture

Abstract

The surgical suture has long been used to reconnect the injured tissues to restore their structure and function. However, its utility remains challenging in many areas, such as surgical site infections and minimally invasive surgeries. Herein, we report a novel surgical suture that possesses both antibacterial activity and shape memory effect to address these issues. In detail, natural antibacterial berberine was incorporated directly into the spinning solution of shape memory polyurethane with a near body transition temperature, and then berberine-containing polyurethane (BP) fibers were prepared by a facile one-step wet-spinning method for surgical suture. The prepared BP fibers were micro-sized and characterized by their transition temperature, morphology, water contact angles, mechanical properties, in vitro shape memory effect, drug release, and antibacterial activity. The results showed that with the increasing amount of the incorporated berberine, the transition temperatures of the fibers were not significantly affected, remains at near body temperature, while the contact angles of the fibers were significantly decreased and the mechanical properties of the fibers were significantly weakened. The optimized fiber was selected to evaluate the cytotoxicity and in vivo biocompatibility before in vivo shape memory effect and wound healing capacity in a mouse skin suture-wound model was tested. Besides the shape memory effect, it was demonstrated that the fiber is capable of antibacterial activity and anti-inflammatory effect, and promoting wound healing. The mechanism of the antibacterial activity and anti-inflammatory effect of the fiber was discussed. Overall, it is expected that by the berberine added to the fiber for surgical suture, it will be more popular and extend the utility of the sutures in a wide range of clinical applications.

Keywords: antibacterial activity; berberine; shape memory; surgical suture; wet spinning.

Figure 1

Schematic presentation of the whole experiment. (A) Synthesis of the SMPU; (B) The one-step wet-spinning method for fiber; (C) In vitro and in vivo assays.

Figure 2

Typical DSC curves (A), stress–strain curves (B), water contact angles (C), and SEM images (D) of the fibers.

Figure 3

Macroscopic pictures for demonstrating the shape memory process (A) and the fixation and recovery ratios of different fibers (B) (mean ± SD, n = 6).

Figure 4

Effects of pH and stretching on the BCH release of the fiber BP-1 (A) and BP-2 (B) (mean ± SD, n = 6).

Figure 5

Colony growth of the fibers against Escherichia coli and Staphylococcus aureus.

Figure 6

(A) Cytotoxicity test on days 1 and 3. Data are presented as the mean ± SD (n = 6). (B) In vivo muscular biocompatibility evaluation of sutures. Representative photos of H&E-stained histological sections of the muscle tissue with BP-0 and BP-1 after implantation for 3 and 7 days. Images on the right were the magnified ones from the left dotted line marked ones. (C) In vivo shape memory assay. The photo series (20°C to 41°C) shows the shrinkage of the fiber while temperature increases (vertical and lateral views for the same temperature).

Figure 7

Mouse skin suture–wound model. Representative photos from four experimental subgroups at different times postoperatively show the wound healing process.

Figure 8

The wound skin tissue was stained with Gram’s crystal violet solution at the end of the experiment on day 9. The black arrow points to Staphylococcus aureus (the scale is 20 µm).

Figure 9

(A) Infrared thermal images of the wounds for mice. (B) Time courses of the wound temperatures for G I and G II. (C) Comparison of the recordings of the temperature for G I and G II using Kruskal–Wallis test. (D) Time courses of the wound temperatures for G III and G IV. (E) Comparison of the recordings of the temperature for G III and G IV using Kruskal–Wallis test. (*P < 0.05).

Figure 10

Hematoxylin–eosin staining of the wound skin tissue. (A) HE staining on day 3 and day 7; Cumulative percentage of neutrophils in random regions of interest by ImageJ software on day 3 (B) and day 7 (C). The scale bar is shown in the figure (one-way ANOVA, mean ± SD, n = 6) (*P < 0.05, **P < 0.001, ***P < 0.001).

Figure 11

Immunohistochemistry of the wound skin tissue. The immunohistochemical staining of pro-inflammatory cytokines TNF-α (A) and IL-1β (D) of the wound skin tissue. Average optical density of TNF-α on day 3 (B) and day 7 (C); Average optical density of IL-1β on day 3 (E) and day 7 (F). The scale bar is shown in the figure (one-way ANOVA, mean ± SD, n = 6) (**P < 0.01, ***P < 0.001).

Figure 12

Proposed pharmacological mechanism of the berberine released from the suture. I Berberine inhibits virulence and infection potential of Staphylococcus aureus through restraining the activities of sortase A (SrtA) and sortase B (SrtB). II Berberine enhances the recruitment of neutrophils. III Berberine plays an anti-inflammatory role by downregulating the expression of cytokines.