Vancomycin Loaded Amino-Functionalized MCM-48 Mesoporous Silica Nanoparticles as a Promising Drug Carrier in Bone Substitutes for Bacterial Infection Management.

Orthopedic infections due to biofilm formation in biomaterial-based implants have become challenging in bone tissue engineering. In the present study, in vitro antibacterial analysis of amino-functionalized MCM-48 mesoporous silica nanoparticles (AF-MSNs) loaded with vancomycin is analyzed for its potential as a drug carrier for the sustained/controlled release of vancomycin against Staphylococcus aureus. The effective incorporation of vancomycin into the inner core of AF-MSNs was observed by alternation in the absorption frequencies obtained by Fourier transform infrared spectroscopy (FTIR). Dynamic light scattering (DLS) and high resolution-transmission electron microscopy (HR-TEM) results show that all the AF-MSNs had homogeneous spherical shapes with a mean diameter of 165.2 ± 1.25 nm, and there is a slight change in the hydrodynamic diameter after vancomycin loading. Furthermore, the zeta potential of all the AF-MSNs (+ 30.5 ± 0.54 mV) and AF-MSN/VA (+ 33.3 ± 0.56 mV) were positively charged due to effective functionalization with 3-aminopropyl triethoxysilane (APTES). Furthermore, cytotoxicity results show that the AF-MSNs have better biocompatibility than non-functionalized MSNs (p < 0.05), and results prove AF-MSNs loaded with vancomycin show better antibacterial effect against S. aureus than non-functionalized MSNs. Results confirm that bacterial membrane integrity was affected by treatment with AF-MSNs and AF-MSN/VA by staining the treated cells with FDA/PI. Field emission scanning electron microscopy (FESEM) analysis confirmed the shrinkage of bacterial cells and membrane disintegration. Furthermore, these results demonstrate that amino-functionalized MSNs loaded with vancomycin significantly increased the anti-biofilm and biofilm inhibitory effect and can be incorporated with biomaterial-based bone substitutes and bone cement to prevent orthopedic infections post-implantation.

Fabrication of Mesoporous Silica Nanoparticle-Incorporated Coaxial Nanofiber for Evaluating the In Vitro Osteogenic Potential.

The most important role of tissue engineering is to develop a biomaterial with a property that mimics the extracellular matrix (ECM) by enhancing the lineage-specific proliferation and differentiation with favorable regeneration property to aid in new tissue formation. Thus, to develop an ideal scaffold for bone repair, we have fabricated a composite nanofiber by the coaxial electrospinning technique. The coaxial electrospun nanofiber contains the core layer, consisting of polyvinyl alcohol (PVA) blended with oregano extract and mesoporous silica nanoparticles (PVA-OE-MSNPs), and the shell layer, consisting of poly-ε-caprolactone blended with collagen and hydroxyapatite (PCL-collagen-HAP). We evaluated the physicochemical properties of the nanofibers using X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). In vitro biocompatibility, cell adhesion, cell viability, and osteogenic potential were evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenlytetrazolium bromide (MTT), calcein AM, and alkaline phosphatase (ALP) activity and Alizarin Red staining in NIH 3T3/MG-63 cells. The results showed that the nanoparticle-incorporated coaxial nanofiber was observed with bead-free, continuous, and uniform fiber morphology with a mean diameter in the range of 310 ± 125 nm. From the biochemical studies, it is observed that the incorporation of nanofiber with HAP and MSNPs shows good swelling property with ideal porosity, biodegradation, and enhanced biomineralization property. In vitro results showed that the scaffolds with nanoparticles have higher cell adhesion, cell viability, ALP activity, and mineralization potential. Thus, the fabricated nanofiber could be an appropriate implantable biomaterial for bone tissue engineering.

Polymeric scaffold of Gallic acid loaded chitosan nanoparticles infused with collagen-fibrin for wound dressing application.

The present study explores the curative efficacy of collagen-fibrin scaffold with Gallic acid loaded Chitosan nanoparticles (GA-CSNPs) in wound healing. GA-CSNPs were synthesized by ionotropic gelation and the incorporation of GA was confirmed with Fourier Transform Infra-Red Spectroscopy (FTIR). Change in the crystal structure of GA was confirmed by X-ray Powder Diffraction (X-PRD) and Differential Scanning Colorimetry (DSC). Surface Electron microscopy (SEM) showed that GA-CSNPs have roughly spherical morphology and mean diameter of 251.3 nm with positive zeta potential. The drug encapsulation was found to be 34.2-73.5%. Col-fibrin scaffolds crosslinked with genipin using cryodesiccation technique showed a sheet-like architecture with 66.78% of crosslinking degree. Scaffolds exhibited porosity of 38.49% and decrease in swelling ratio. Biodegradation study demonstrated controlled degradation with collagenase and Thermogravimetric analysis (TGA) showed excellent thermal stability and sustained drug release property. In vitro and in vivo study results indicate that the group treated with nanocomposite scaffold exhibits enhanced re-epithelialization, accelerated fibroblast cell migration, wound healing and significant wound contraction (p < 0.001) compared to control. Nanocomposite scaffolds also accelerates angiogenesis, hexosamine synthesis, collagen deposition and recruiting immune cells at wound area. These results suggest nanocomposite scaffold values for their use as a promising wound dressing material for better tissue regeneration.

Fibrin hydrogel incorporated with graphene oxide functionalized nanocomposite scaffolds for bone repair - In vitro and in vivo study.

Conventional bone repair therapies like the autologous and allogenic bone grafts have failed to meet challenges in bone reconstruction along with complications. Tissue engineering (TE) has emerged as a developing treatment regimen in regenerating damaged tissues rather than replacing them. In TE, biomaterials act as template for damaged tissues and function as artificial extracellular matrix (ECM), facilitating new tissue formation. Since single type biomaterial has unsuccessful regeneration properties, focus on using composites of natural and synthetic biomaterials is encouraged. In the current study, we have evaluated the potential of a graphene-based nano-composite scaffold as a biomaterial to enhance bone tissue regeneration. The findings demonstrate that the scaffold with Graphene oxide (GO) exhibits enhanced levels of biocompatibility, alkaline phosphatase activity, and calcium deposits, thereby emphasizing the hypothesis that fabricated nanocomposite scaffolds are promising osteoinductive products for bone repair/regeneration.