An innovative ciprofloxacin-infused silk hernia mesh for abdominal wall repair and infection control

Abdominal wall hernia (AWH) is the common problem in which internal organs are pushed through a hole in the abdominal wall causing pain and discomfort in that area. The risk factors includes obesity, genetic conditions, trauma, and constant heavy lifting [1,2]. The most common forms of hernias are abdominal wall hernia, inguinal hernia and incisional hernia in which the tissues were incompletely healed from previous surgery or other damage. It is affecting at least 15 in 1000 population (1.5 %) and 2 % of men and is a significant cause of morbidity in the adult population worldwide. More than 20 million hernia repairs are performed annually and represent a significant burden to the healthcare system [3]. In some research, the incidence of incisional hernias was as high as 4–10 % which brought a heavy burden to society. Therefore, a lot of research contributes towards developing better scaffolds and meshes to cure abdominal wall hernia and prevent its relapse. Mechanically strong meshes provide tension-free repair by creating a bridge and reinforce normal anatomical structure of abdominal wall [4,5]. Different cell growth factors start to accumulate near the surgical mesh that provide strength and facilitate the process of cell proliferation. Depending upon the surrounding organs and hernia site, the mesh must fulfill certain biological standards. Cell proliferation is considered important parameter for any mesh because good cellular response indicates the biocompatibility of material which promotes tissue regeneration and rapid healing [6]. Non-absorbable synthetic meshes, such as polytetrafluoroethylene (PTFE), polypropylene (PP) and polyester (PE), are the most commonly used meshes that provide excellent mechanical strength [7] but are also associated with rigidity, leading to chronic inflammatory tissue reactions, cell adhesion and other complications. On the other hand, absorbable meshes facilitate cell proliferation and discharge from the surgical site including polyglycolic acid (PGA), poly-4-hydroxybutyrate (P4HB), poly-p-dioxanone (PDO), polylactic acid (PLA), and silk fibroin. Therefore, the selection of mesh material plays a critical role in healing response after surgery.

As one of strongest natural fibers with high ultimate tensile strength of 300–740 MPa, the medical application of silk fibroin (SF) as surgical sutures, has been well documented. It provides excellent biocompatibility, flexibility, high efficiency, controlled drug delivery without any unnecessary immune response. The structure of SF contains amorphous and crystalline zone with amino acids that impart some adsorption effect on cells. It was able to adsorb peritoneal mesenchymal cells that produce hepatocyte growth factor (HGF), which stimulates the migration and proliferation of mesenchymal cells, and express transforming growth factor-β antibodies. It can also boost the formation of neovascularization and depict anti-infection effect. The use of silk biomedical textiles and fiber-based mesh has also been explored for tissue repair and cell regeneration [8]. Kaixianf Gao et al., prepared silk fibroin solution and studied the effect of different concentrations of SF in scaffolds on cell proliferation [9]. Xiaojiao Liu et al., modified silk fibroin electrospun scaffolds to evaluate their corresponding impact on cell proliferation and osteogenesis [10]. Pasquale Sacco et al., developed silk fibroin enriched 3D bioink constructs that enable cell proliferation [11]. Manabu Yamada et al., prepared silk fibroin sponges that provide good attachment, cell viability and cell proliferation [12]. To the best of our knowledge, there are only few reports on the use of silk fibroin for the development of hernia meshes [13].

Infections caused by various bacterial attacks during surgeries are generally difficult to treat because they require long periods of antibiotic therapy and repeated surgical procedures in some cases. Only few authors suggest the application of meshes incorporated with broad-spectrum antibiotics that helps to combat infections at surgical site that delayed cell proliferation [14]. Ciprofloxacin (CIF) is a third-generation fluoroquinolone drug with broad-spectrum antibacterial activity [15]. R Kaveti et al., functionalized bioresorbable electronic surgical mesh (BESM) with CIF that treat adhesion formation and infections [16]. S Nosheen et al., incorporated chitosan and bacterial cellulose (MD) on polypropylene mesh for the treatment of bacterial infection against E.coli [17]. BS Heidari et al., developed 3D printed PP and PVA meshes with CIF loading that possess excellent mechanical strength [18]. Tran et al., studied the application of silk fibroin/chitosan nanofibrils for drug delivery system [19]. Fluoroquinolones inhibit DNA replication in bacteria because their mechanism of action is the inhibition of bacterial DNA gyrase and topoisomerase IV. The lack of cross-resistance between fluoroquinolones and other classes of antibiotics makes this antibiotic family important. CIF and its derivatives can effectively treat antibiotic-resistant infections (e.g., nosocomial pneumonia), so they are usually reserved as “drugs of last resort”. Since CIF is active against many gram-negative and gram-positive bacteria, it is used for complicated abdominal or urinary tract infections. In addition, this antibiotic has shown the potential to penetrate tissues and destroy bacterial biofilms.

In this research, a novel absorbable biocompatible knitted mesh was fabricated and embedded with CIF for the effective treatment of AWH and to overcome the post-surgical issues related to mesh implants. Moreover, CIF coating with silk fibroin solution on silk knitted meshes has added a new dimension to the already existing knowledge. In literature, CIF was used for the modification of PP based meshes, while its incorporation into silk mesh has not been reported yet. The mesh material used was manufactured from 100 % pure double plied silk yarn based on natural silk fibers obtained from Bombyx mori cocoons and was knitted in two weft knitting patterns: a loose knitted and a dense knitted fabric. The meshes were coated with silk fibroin solution that acted as a reinforcement to provide structural integrity, and as a medium to successfully incorporate ciprofloxacin drug into the mesh structure.

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