Treatment of osteomyelits and fractures with critical bone loss in experiments on rats using biocomposites containing nanocapsular polymer systems for intracellular delivery of BMP-coding plasmids, tenoxicam and vancomycin

BACKGROUND: Osteomyelitis remains a significant issue associated with a high frequency of recurrence and a substantial risk of serious complications. The situation is exacerbated by the increasing antibiotic resistance, which reduces the effectiveness of traditional antibacterial therapies. In this regard, the search for new methods of treating osteomyelitis becomes particularly relevant, especially in cases accompanied by extensive bone loss.

AIM: This study tested an approach for osteomyelitis treating using biocomposite bone implants based on a matrix of washed bovine spongiosa bone, with a complex medicinal function providing local antibacterial, anti-inflammatory and bone-regenerative effects. The effectiveness of the approach was assessed using a model of experimental rat osteomyelitis.

MATERIALS AND METHODS: The research involved developing polysaccharide gels with mechano-rheological properties similar to those of soft tissues (G‘=176–271 kPa, G’=3.7–4.2 kPa), containing amikacin and vancomycin (250 mg/g of dry polymer), tenoxicam (0.28 mg/ml), and a BMP-coding plasmid (12.83 ng/ml), providing the implants with local antibacterial, directed anti-inflammatory effects, and bone tissue growth stimulation. Two types of nanocorpuscular carriers with different diameters were incorporated into the gel: hyaluronic gel nanoparticles with a bimodal size distribution (d=100 and 3000 nm) for the delivery of tenoxicam into phagocytic immunocompetent cells, and nanocapsules coated with a transfection agent (d=50–100 nm) to facilitate transmembrane transport of the plasmid into non-phagocytic cells, where ribosomes synthesize BMP-2 to initiate cell differentiation along the bone pathway. Antibiotics are released from the carrier only at the moment of bacterial attack of the implant under the action of bacterial enzymes and provide their local concentration 200 times exceeding the bactericidal one. Cytotoxicity in recalculation on dry gel is 1800 µg/ml. The minimum inhibitory concentration against Staphylococcus aureus 209P is 25 µg/ml, bactericidal concentration is 100 µg/ml.

RESULTS: It was found that biocomposites impregnated with drug gel effectively inhibit local bacterial infections, reduce the overall level of local aseptic inflammation, and promote bone regeneration in osteomyelitis.

CONCLUSIONS: The methodological approach to treating purulent-septic inflammation complicated by bone tissue loss, using implants with complex drug functions, shows promise.