Replacement of autogenous or allograft bones by artificial graft materials represents a growing area of interest in current bone repair strategies. Bioactive ceramics in particulate form, such as Bioglass (BG) 45S5, stimulate bone mineralization comparable to autologous bone grafts, but have potential issues of particle migration and inflammation. The aim of this study was to employ a chondroitin sulfate- (CS-) based bioadhesive to improve integration of the bioglass (NovaBone Putty) to prevent particle migration and promote bone regeneration. This BG-CS composite can encapsulate bone marrow (BM) to form a mechanically stable construct, BG-CS-BM. Rheological characterization confirmed the formation of CS-BM hydrogel by reacting the CS-based bioadhesive with the BM. Compared to the bioglass, the BG-CS-BM composite demonstrated a superior capacity to maintain construct integrity under both aqueous and turbulent environments in vitro. After implantation for 4 weeks in a critical-size distal femoral bone defect in a rabbit model, there was significantly greater bone growth in BG-CS-BM as compared to bioglass-only and the empty control. Unlike BG-CS-BM, BG-CS recruited BM in situ from the bone defect. BG-CS demonstrated a similar effect in bone formation but at a comparatively slower rate than BG-CS-BM over 6-weeks' implantation.
Tissue-engineering strategies offer promising tools for repairing cartilage damage; however, these strategies suffer from limitations under pathological conditions. As a model disease for these types of nonideal systems, the inflammatory environment in an osteoarthritic (OA) joint limits the efficacy of engineered therapeutics by disrupting joint homeostasis and reducing its capacity for regeneration. In this work, we investigated a sugar-based drug candidate, a tributanoylated N-acetyl-d-glucosamine analogue, called 3,4,6-O-Bu3GlcNAc, that is known to reduce nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in osteoarthritis. 3,4,6-O-Bu3GlcNAc not only inhibited NFκB signaling but also exerted chondrogenic and anti-inflammatory effects on chondrocytes isolated from patients with osteoarthritis. 3,4,6-O-Bu3GlcNAc also increased the expression of extracellular matrix proteins and induced cartilage tissue production in three-dimensional in vitro hydrogel culture systems. To translate these chondrogenic and anti-inflammatory properties to tissue regeneration in osteoarthritis, we implanted 3,4,6-O-Bu3GlcNAc-loaded poly(lactic-co-glycolic acid) microfiber scaffolds into rats. The drug-laden scaffolds were biocompatible, and when seeded with human OA chondrocytes, similarly promoted cartilage tissue formation. 3,4,6-O-Bu3GlcNAc combined with the appropriate structural environment could be a promising therapeutic approach for osteoarthritis.
Antibiotic use for ocular treatments has been largely limited by poor local bioavailability with conventional eyedrops formulations. Here, we developed a controlled delivery system composed of moxifloxacin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated in a chondroitin sulfate-based, two-component bioadhesive hydrogel. Using a simple and fast electrohydrodynamic spray drying (electrospraying) technique, surfactant-free moxifloxacin-loaded microparticles were fabricated with diameters on the order of 1 μm. A mixed solvent system of methanol/dichloromethane (MeOH/DCM) was employed to prepare the microparticles for the electrospraying processing. Extended release of moxifloxacin using a series of MeOH/DCM mixed solvents was accomplished over 10 days with release concentrations higher than the minimum inhibitory concentration (MIC). In contrast, moxifloxacin loaded directly in hydrogels was released rapidly within 24 h. We observed a decrease of the drug release rate from the microparticles when using an increased percentage of methanol in the mixed solvent from 10% to 30% (v/v), which can be explained by the mixed solvent system providing a driving force to form a gradient of the drug concentrations inside the microparticles. In addition, the delivery system developed in this study, which incorporates a bioadhesive to localize drug release by in situ gelling, may potentially integrate antibiotic prophylaxis and wound healing in the eye.
Morphology and mechanical properties of scaffolds seeded with osteoblastes cells used for bone and cartilage repair are the critical factors in bone tissue engineering. In this work, adding CMC and controlling temperature for nano-hydroxyapatite (HA)-b-tricalcium phosphate (b-TCP) scaffold using Polymeric sponge method provide suitable properties. A developed computer system was used to determine properties of scaffold. Porosity, shape and connectivity of pores were analysed based on image processing method. Cells were seeded on scaffold and the differentiation rate was calculated using image analysis. The fabricated sample showed high porosity (nearly 61%) and high compressive strength (nearly 16 MPa), as well as having a well pore size of 200 μm and more. Comparing to Archimedes method, the image result was more accurate. Internal porosity was more than surface porosity due to skin effect.
Orthopaedic implants and metal implantation are major technological contributions in the field of orthopaedic surgery. However, bacterial infection and inflammation are predicament issues that subsequently lead to implant failure and second surgery. Ceramic scaffold loaded with gold nanoparticles (Au NPs) posse's antimicrobial and anti-inflammatory properties, which would be more ideal for successful bone implantation and tissue regeneration. Thereby, Hydroxyapatite nanoparticles (nHA), β-Tricalcium Phosphate nanoparticles (nβ-TCP), and Au NPs were used for the fabrication of ceramic scaffold and Au NPs loaded ceramic scaffold. The effects of the Au NPs on the scaffold's mechanical properties, porosity and cell growth have been evaluated. Scanning Electron Microscope [1] and test metric universal testing machine were employed for characterization of the scaffolds. Gold loaded scaffold demonstrated enhanced porosity, degradability and mechanical properties compared with the ceramic scaffold. The porosity of the ceramic and Au NPs loaded ceramic scaffold ranged between 30-50% and 60-75%, respectively, while compressive strength ranged between 10-30mPa and 25-45mPa, respectively.. Scaffold synthesis can be used for implantation in organs that need high load bearing such as femurs, tibia and also as a substrate for Au NPs delivery. To our knowledge, Au NPs have not been incorporate previously with calcium phosphate for fabrication scaffold for bone grafting. Also this study the first report on the effects of Au NPS on the mechanical properties, porosity and degradation rates of ceramic scaffolds.
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