Vancomycin-releasing cross-linked collagen sponges as wound dressings

Abstract

The study presents a novel vancomycin-releasing collagen wound dressing derived from Cyprinus carpio collagen type I cross-linked with carbodiimide which retarded the degradation rate and increased the stability of the sponge. Following lyophilization, the dressings were subjected to gamma sterilization. The structure was evaluated via scanning electron microscopy images, micro-computed tomography, and infrared spectrometry. The structural stability and vancomycin release properties were evaluated in a phosphate buffer solution. Microbiological testing and a rat model of a wound infected with methicillin-resistant Staphylococcus aureus (MRSA) were then employed to test the efficacy of the treatment of the infected wound. Following an initial mass loss due to the release of vancomycin, the sponges remained stable. After 7 days of exposure in phosphate buffered saline (37°C), 60% of the material remained with a preserved collagen secondary structure together with a high degree of open porosity (over 80%). The analysis of the release of the vancomycin revealed the homogeneous distribution of the antibiotic both across and between the sponges. The release of vancomycin was retarded as proved by in vitro testing and further confirmed by the animal model from which measurable concentrations were observed in blood samples 24 hours after the subcutaneous implantation of the sponge, which was more than observed following i. p. administration. The sponge was also highly effective in terms of reducing the number of colony-forming units in biopsies extracted from the infected wounds 4 days following the inoculation of the wounds with the MRSA solution.

Controlled Delivery of Vancomycin from Collagen-tethered Peptide Vehicles for the Treatment of Wound Infections

“…The cumulative release of free vancomycin from the matrices was close to 70− 80% at the initial 8 h time point, similar to previous reports of vancomycin release from collagen-based scaffolds. 32,54,55 In contrast, the vancomycin release from ECnVs, over the initial 8 h, from both collagen (K i = 0.61) and co-gel (K i = 0.57) matrices, was significantly slower (p < 0.05) than free vancomycin release from the matrices (collagen (K i = 0.80) and co-gel (K i = 0.68)). These data suggest that the early release of the vancomycin from the loaded ECnVs likely resulted from nontethered vancomycin-loaded carriers on matrices rather than from the presence of free vancomycin.…”

An Additively Manufactured Sample Holder to Measure the Controlled Release of Vancomycin from Collagen Laminates

“…As an additional hour of incubation in solution did not show any further release of vancomycin, the sample holder should not influence the total amount of released vancomycin. Furthermore, the incomplete release of vancomycin from crosslinked collagen has already been described in literature [17,25]. However, the effect of compression caused by the sample holder as well as the re-swelling of hydrogels after compression should not be neglected.…”

“…Vancomycin has also been used to impregnate collagen/hydroxyapatite layers coated on titanium implants to prevent infections and improve implant integration into the bone [16]. Hartinger et al showed that natural biomaterials such as collagen, which was crosslinked by carbodiimide, can also be used for the controlled release of vancomycin [17].…”

“…As a natural biomaterial, collagen is commonly used in regenerative medicine as it is biocompatible and is degraded to non-toxic peptides and amino acids [18][19][20][21]. Its properties can be modified by crosslinking, e.g., by glutardialdehyde [22] or carbodiimide [17,23], physical crosslinking by UV-irradiation or dehydrothermal treatment [24], or photochemical crosslinking, for which rose bengal (RB) and green light crosslinking (RGX) is a prominent example [25]. RGX-modified collagen sheets have already been used for the controlled release of vancomycin [25].…”

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

“…We previously tested a homogeneous spongy matrix based on gentamicin- and vancomycin-containing homogeneous fresh water fish collagen cross-linked with carbodiimide as a wound dressing in a rat surgical site infection model [ 21 , 22 ]. The presented study also involved the further modification of the structure of the sponge and the testing of its characteristics as a potential carrier of rifampin.…”