<p>Injectable Chitosan-Based Thermosensitive Hydrogel/Nanoparticle-Loaded System for Local Delivery of Vancomycin in the Treatment of Osteomyelitis</p>

Abstract

Purpose: Osteomyelitis, particularly chronic osteomyelitis, remains a major challenge for orthopedic surgeons. The traditional treatment for osteomyelitis, which involves antibiotics and debridement, does not provide a complete solution for infection and bone repair. Antibiotics such as vancomycin (VCM) are commonly used to treat osteomyelitis in clinical settings. VCM use is limited by a lack of effective delivery methods that provide sustained, high doses to entirely fill irregular bone tissue to treat infections. Methods: We engineered a chitosan (CS)-based thermosensitive hydrogel to produce a VCM-nanoparticle (NPs)/Gel local drug delivery system. The VCM-NPs were formed with quaternary ammonium chitosan and carboxylated chitosan nanoparticles (VCM-NPs) by positive and negative charge adsorption to enhance the encapsulation efficiency and drug loading of VCM, with the aim of simultaneously preventing infection and repairing broken bones. This hydrogel was evaluated in a rabbit osteomyelitis model. Results: The VCM-NPs had high encapsulation efficiency and drug loading, with values of 60.1±2.1% and 24.1±0.84%, respectively. When embedded in CS-Gel, the VCM-NPs maintained their particle size and morphology, and the injectability and thermosensitivity of the hydrogel, which were evaluated by injectability test and rheological measurement, were retained. The VCM-NPs/Gel exhibited sustained release of VCM over 26 days. In vitro tests revealed that the VCM-NPs/Gel promoted osteoblast proliferation and activity against Staphylococcus aureus. In vivo, VCM-NPs/Gel (with 10 mg vancomycin per rabbit) was used to treat rabbits with osteomyelitis. The VCM-NPs/Gel showed excellent anti-infection properties and accelerating bone repair under osteomyelitis conditions. Conclusion: The reported multifunctional NPs hydrogel system for local antibiotic delivery (VCM-NPs/Gel) showed bone regeneration promotion and anti-infection properties, demonstrating significant potential as a scaffold for effective treatment of osteomyelitis.

Advances in Growth Factor Delivery for Bone Tissue Engineering

“…Nonetheless, cellulose hydrogels show restricted mechanical attributes that hold back their utilization in hard tissue applications. To surpass this limitation of cellulose-based scaffolds and to build on the functional properties for hard tissue application, mineralization of cellulose hydrogels with HAp and other materials has been actively investigated in recent years [ 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ]. Bacterial cellulose was successfully combined with HAp to deliver BMP-2 [ 94 ].…”

“…Chitin–chitosan is a nitrogen-containing polysaccharide-based biopolymer group derived from diverse natural raw materials such as fungi, crustaceans, and insects [ 96 , 97 ]. Chitin and chitosan are structurally similar to glycosaminoglycans (GAGs, the major component of the bone ECM), which make them suitable biopolymers for tissue engineering scaffolds [ 96 , 97 , 98 ]. Chitin used in combination with chitosan/poly(vinyl alcohol) to fabricate nanofibers showed enhanced mechanical properties and offered osteoblast cell growth with HAp biomineralization [ 99 ].…”

“…Sci. 2021, 22, x FOR PEER REVIEW 9 of 35 based scaffolds and to build on the functional properties for hard tissue application, mineralization of cellulose hydrogels with HAp and other materials has been actively investigated in recent years [90][91][92][93][94][95][96][97][98][99][100]. Bacterial cellulose was successfully combined with HAp to deliver BMP-2 [94].…”

Review on Computer-Aided Design and Manufacturing of Drug Delivery Scaffolds for Cell Guidance and Tissue Regeneration

“…Temperature-responsive hydrogels, made of lower critical solution temperature (LCST) polymers, are liquid below a critical solution temperature and become a gel above it. Physiological gelation temperatures enable injectable materials, such as poly( N -isopropylacrylamide) (PNIPAAm) and chitosan-based solutions, to be administered through a syringe and gel upon injection into the body, where they may serve as a drug or biomolecule reservoir ( Pal et al, 2020 ; Tao et al, 2020 ). PNIPAAm features hydrophilic amide groups, which are buried during its coil-to-globule transition above the LCST point, and hydrophobic isopropyl groups, which are conversely exposed.…”

Synthesis And Characterization of Vancomycin-Loaded Chitosan Nanoparticles For Drug Delivery

“…Methicillin-resistant S. aureus and multidrug-resistant mycobacteria are drug-resistant pathogens, which can develop persistence in the intracellular locations after drug treatment. Many researches have been done on the vancomycin loaded nanoparticles, especially CSNPs [16][17][18][19][20][21][22].…”