Sustainable Release of Vancomycin from Silk Fibroin Nanoparticles for Treating Severe Bone Infection in Rat Tibia Osteomyelitis Model

Abstract

The successful treatment of bone infections is a major challenge in the field of orthopedics. There are some common methods for treating bone infections, including systemic antibiotic administration, local nondegradable drug vehicles, and surgical debridement, and each of these approaches has advantages and disadvantages. In the present study, the antibiotic vancomycin (VANCO) was loaded in silk fibroin nanoparticles (SFNPs) and the complexes were then entrapped in silk scaffolds to form sustained drug delivery systems. The release kinetics of VANCO from SFNPs alone and when the SFNPs were entrapped in silk scaffolds were assessed at two different pH values, 4.5 and 7.4, that affected the release profiles of VANCO. Disk diffusion tests performed with pathogens causing osteomyelitis methicillin-resistant Staphylococcus aureus (MRSA) showed antibacterial activity of the released drug at two different pH values. Additionally, injection of 8 × 10 CFU MRSA in rat's tibia induced severe osteomyelitis disease. Radiographic and histopathological analyses were performed to evaluate the effectiveness of treatment after 6 weeks. The VANCO-loaded silk fibroin nanoparticles entrapped in scaffolds reduced bone infections at the defected site with better outcomes than the other treatment groups. In conclusion, the delivery system with good biocompatibility and sustained release properties would be appropriate for further study in the context of osteomyelitis disease.

Therapeutics and delivery vehicles for local treatment of osteomyelitis

“…123 Despite successes with ALBC, standardized protocols, studies elucidating minimum effective dosing against biofilm, and efficacy in randomized controlled trials are warranted. 122 poly(N-isopropylacrylamide) (PNIPAM), 129 gold, 47,94,130 silver, 94,131 silk fibroin, 94,127 chitosan, 132 chitosan/silver-hydroxyapatite blends, 133 and PLGA. 105,112,126,128 Chitosan-glycerophosphate, 110 gelatin, 102 and a mixture of chitosan and gelatin cross-linked with genipin have also been used.…”

Bio-inspired anisotropic polymeric heart valves exhibiting valve-like mechanical and hemodynamic behavior

“…SFs, natural polymer proteins extracted from silk, have been widely applied to artificial scaffolds and tissue engineering, such as soft tissue repair [31], bone regeneration [32] and drug delivery [33], owing to their good biocompatibility, mechanical stability and tunable properties [34]. Electrospun nanofibrous materials offer pre-cise porosity and architecture, which have shown mechanical properties, such as elastic modulus and tensile strength, similar to some native tissues [17,35,36].…”

Silk‐Based Antimicrobial Polymers as a New Platform to Design Drug‐Free Materials to Impede Microbial Infections

“…By engineering novel polymers with intrinsic antimicrobial or anti‐infective properties, new and smarter biomaterials can be developed. In the present study, SF was chosen as a backbone structure in order to develop multifunctional films, since this natural protein polymer has outstanding properties and has been widely used to produce different types of biomaterials from films to fibers and other variants …”

“…Current strategies to prevent SSI rely mostly on the local administration of antibiotics or antibacterial agents to the implant site . The incorporation of antibiotics on fibers or as coatings in medical devices, like surgical sutures, help prevent the adherence and formation of microbial biofilms . However, this approach may have a negative effect by increasing microbial resistance to antibiotics, ultimately failing to prevent SSI.…”

“…Among the different types of spider silk, the major ampullate dragline silk from Nephila clavipes is one of the most extensively studied silks due to the mechanical properties . Similarly, SF is commonly used as a biomaterial due to its biocompatibility, biodegradability, mechanical properties, water vapor permeability, and minimal inflammatory response …”