Electroactive and antibacterial surgical sutures based on chitosan-gelatin/tannic acid/polypyrrole composite coating

Highlights

• Functional sutures were fabricated by decorating the surface with CS-GE/TA/PPy composite coating.

• The functional sutures had conductivity even knotted, ensuring stable electrical signal transmission.

• The functional sutures exhibited superior antibacterial properties against E. coli and S. aureus.

• The electroactive and antibacterial sutures significantly enhanced tissue regeneration.

Abstract

Surgical sutures pervade almost all surgeries; however, their clinical therapy effects are barely satisfactory due to the lack of physiological signal responsiveness and the prone surgical site infection (SSI). Herein, the functional sutures (PCGT@S) with electroactivity and antibacterial properties were fabricated by decorating the suture surfaces with chitosan-gelatin/tannic acid/polypyrrole (CS-GE/TA/PPy) composite coating. Thanks to the assistance of CS-GE/TA on the polymerization of PPy, the inherent brittleness of PPy was alleviated and ensured PCGT@S excellent conductivity even under knotted state, thereby providing stable physiological electrical signal transmission among cells and regulating cell behaviors actively. Meanwhile, the synergistic effects of CS-GE/TA and PPy offered PCGT@S outstanding antibacterial rates of over 99% against E. coli and S. aureus without involving any additional drugs. Furthermore, in vivo studies revealed that PCGT@S could enhance wound healing dramatically, as evidenced by less inflammatory reaction, better angiogenesis, cell proliferation, re-epithelization, granulation tissue, and collagen regeneration. This study successfully demonstrates the feasibility of the electroactive and antibacterial sutures for promoting tissue regeneration and provides a new idea for exploring the next generation bioactive suture.

Introduction

Surgical sutures are omnipresent medical devices used for nearly all tissue repairs, with a global market value of $5.84 billion by 2023 [1]. Hitherto, hundreds of non-absorbable and absorbable sutures have been developed to cater to the enormous market demand [2]. Although most sutures can provide sufficient mechanical support, the clinical therapeutic effects are unsatisfactory because of their disability in actively participating in wound healing, which undoubtedly brings extra pressure on patients and society. Therefore, it is highly imperative to exploit bioactive sutures to facilitate wound healing. It has been reported that the lateral wound electric field (EF) will be formed from the surrounding intact tissue toward the center of the wound after a wound happens [3]. The effective transmission of the electrical signals generated by wound EF can modulate cell behaviors, including adhesion, proliferation, migration, and differentiation, thereby accelerating wound healing [[3], [4], [5]]. With this in mind, the electroactive surgical sutures with physiological electrical signal response-ability may significantly improve wound healing and tissue regeneration. However, to our best knowledge, electroactive sutures are rarely reported so far.

Conductive materials have been introduced to efficiently conduct and distribute electrical signals [6,7]. Among various conductive materials, polypyrrole (PPy) is one of the most widely investigated in the biomedical field due to its low cost, easy synthesis, high electrical conductivity, and good biocompatibility [8,9]. Besides, it has been demonstrated that PPy can support cell adhesion, growth, and differentiation [4]. However, being the same as the other conductive polymers, a single-component PPy suture cannot be constructed because of its poor tensile strength. Thus, incorporating PPy onto the sutures via proper surface modification is a preferred strategy to develop electroactive sutures. However, noticeably, the inherent rigidity and brittleness of PPy make it unsuitable to be used alone for surface modification of surgical sutures that need to be bent and knotted during operation [10]. Understandably, pure PPy coating is vulnerable to breaking or falling off from the suture surface, leading to a discontinuous electrical signals transmitting pathway. Therefore, to obtain practical electroactive sutures, how to overcome the brittleness of PPy and ensure stable conductivity is a critical issue that deserves to be considered deeply.

Another well-documented clinical issue of surgical sutures is surgical site infection (SSI) [11,12]. Various antibacterial sutures have been developed to reduce SSI by coating antibiotics or metal ions onto the suture surface [[13], [14], [15]]; the problems of uncontrolled drug release, drug resistance, and biological security cannot be ignored. Therefore, creating functional sutures, especially those combining electroactivity and antibacterial property, is a formidable task.

Herein, we proposed a facile strategy to address the challenges mentioned above. A composite coating integrating stable conductivity and antibacterial property was constructed on the suture surface by taking the tannic acid crosslinked chitosan-gelatin (CS-GE/TA) as the skeleton to assist in situ polymerization of PPy. The rich hydroxy and amine groups in CS-GE could form affinities with the Py monomer through non-covalent bond interactions [10]. TA, containing five pyrogallol and five catechol groups, can crosslink CS-GE by multiple interactions and act as the crosslinking agent and dopant during the polymerization process of PPy [16]. Thanks to the assistance of CS-GE/TA pre-coating on the polymerization of PPy, the inherent fragility of PPy could be efficiently alleviated, and thereby the sutures could maintain stable conductivity. Additionally, TA and PPy have been proved to possess excellent antibacterial and anti-inflammatory performance [17,18], which is of profound significance for reducing infection and inflammation at the wound site without involving additional drugs. The morphology, mechanical performance, and conductivity of the sutures could be well controlled by adjusting the preparation process. Furthermore, the biocompatibility, antibacterial behavior, and in vivo experiments were performed to verify their potential in promoting wound healing and regeneration.