Rifampin-Releasing Triple-Layer Cross-Linked Fresh Water Fish Collagen Sponges as Wound Dressings

Abstract

Objectives. Surgical wounds resulting from biofilm-producing microorganisms represent a major healthcare problem that requires new and innovative treatment methods. Rifampin is one of a small number of antibiotics that is able to penetrate such biofilms, and its local administration has the potential to serve as an ideal surgical site infection protection and/or treatment agent. This paper presents two types (homogeneous and sandwich structured) of rifampin-releasing carbodiimide-cross-linked fresh water fish collagen wound dressings. Methods. The dressings were prepared by means of the double-lyophilization method and sterilized via gamma irradiation so as to allow for testing in a form that is able to serve for direct clinical use. The mechanical properties were studied via the uniaxial tensile testing method. The in vivo rifampin-release properties were tested by means of a series of incubations in phosphate-buffered saline. The microbiological activity was tested against methicillin-resistant staphylococcus aureus (MRSA) employing disc diffusion tests, and the in vivo pharmacokinetics was tested using a rat model. A histological examination was conducted for the study of the biocompatibility of the dressings. Results. The sandwich-structured dressing demonstrated better mechanical properties due to its exhibiting ability to bear a higher load than the homogeneous sponges, a property that was further improved via the addition of rifampin. The sponges retarded the release of rifampin in vitro, which translated into at least 22 hours of rifampin release in the rat model. This was significantly longer than was achieved via the administration of a subcutaneous rifampin solution. Microbiological activity was proven by the results of the disc diffusion tests. Both sponges exhibited excellent biocompatibility as the cells penetrated into the scaffold, and virtually no signs of local irritation were observed. Conclusions. We present a novel rifampin-releasing sandwich-structured fresh water fish collagen wound dressing that has the potential to serve as an ideal surgical site infection protection and/or treatment agent.

Review on the fish collagen-based scaffolds in wound healing and tissue engineering

“…From Table 1, it is evident that collagen was used as the biomaterial and certain studies have extracted collagen from a specified fish scale while few other studies have not specified the species of the fish collagen. Of the 10 studies included in this review, 4 studies have extracted collagen from tilapia (Sun et al, 2021;Wang et al, 2021;Zhou et al, 2017), 1 study extracted collagen from Panaeolus olivaceus (Chandika et al, 2021), 1 study extracted collagen from Cyprinus carpio (Hartinger et al, 2020) 1 study extracted collagen from Ctenopharyngodon idellus (Shi et al, 2020), 1 study extracted collagen from Scyliorhinus canicula (Lahmar et al, 2022) 2 studies have not specified the fish species because both these studies obtained fish collagen from laboratories.…”

“…depicts the variables assessed in the included studies, species/strain, age, weight, skin wound size, animal sex, implantation period and protocol of treatment. The animal models used for these are ICR mice (Chandika et al, 2021), Wistar rats (Hartinger et al, 2020) Sprague-Dawley rats (Hu et al, 2021;Sun et al, 2021;Wang et al, 2021;Zhou et al, 2017) New Zealand White rabbits (Shi et al, 2020), BALB/c albino rats (Lahmar et al, 2022) Mice (Li et al, 2018). Five Studies used male animals (Chandika et al, 2021;Hu et al, 2021;Sun et al, 2021;Zhou et al, 2017) remaining five studies have not specified the sex of the animal model.…”

“…The weight of the animal varied mostly between 200-380g in the nine studies reported except for one study where the weight of the mice reported was 30g (Chandika et al, 2021). The skin wounds were of 3 different types, five studies performed excision wounds (Chandika et al, 2021;Hu et al, 2021;Lahmar et al, 2022;Zhou et al, 2017), three studies performed Incision wounds (Hartinger et al, 2020;Li et al, 2018;Wang et al, 2021) and two studies performed on burn wounds (Shi et al, 2020;Sun et al, 2021). The wound size varied from 0.5 to 2 cm.…”

“…Most of the studies used one-time treatment and there was no change of dressing or scaffold. The scaffolds were inserted and sutured (Hartinger et al, 2020;Hou et al, 2020;Li et al, 2018;Shi et al, 2020;Sun et al, 2021;Wang et al, 2021). One study changed the dressing at regular intervals of two days (Lahmar et al, 2022).…”

Application of marine collagen for stem‑cell‑based therapy and tissue regeneration (Review)

“…By combining with rifampin, a fish collagen-based wound dressing was produced. This type of wound dressing demonstrated good mechanical properties and exhibited desirable biocompatibility, since the cells penetrated into the sponge and virtually no signs of local irritation were observed ( 88 ). Recently, collagen from the fish scale of Larimichthys crocea was extracted and a hybrid hydrogel based on this collagen was developed for wound healing ( 89 ).…”