Nanofibrous Scaffolds Containing Hydroxyapatite and Microfluidic-Prepared Polyamidoamin/BMP-2 Plasmid Dendriplexes for Bone Tissue Engineering Applications.

OBJECTIVE: The aim of this study is to fabricate functional scaffolds to gene delivery bone morphogenetic protein-2 (BMP-2) plasmid for bone formation in bone tissue engineering. METHODS: Dendriplexes (DPs) of generation 4 polyamidoamin (G4-PAMAM)/BMP-2 plasmid were prepared through microfluidic (MF) platform. The physiochemical properties and toxicity of DPs were evaluated by DLS, AFM, FESEM and MTT assay. In order to create a suitable environment for stem cell growth and differentiation, poly-l-lactic acid (PLLA) and poly-l-lactic acid/poly (ethylene oxide) (PLLA/PEO) scaffolds containing hydroxyapatite nanoparticles (HA) and DPs were fabricated by the electrospinning method. The osteogenic potency of the scaffolds on human adipose tissue-derived mesenchymal stem cells (hASCs) was investigated. RESULTS: The results revealed that tuning the physical properties of DPs by adjusting flow parameters in microfluidic platform can easily improve the cell viability compared to conventional bulk mixing method. Also, the result showed that the presence of HA and DPs in PLLA/PEO scaffold enhanced alkaline phosphatase (ALP) activity and increased the amount of deposited Ca, as well as, related to osteogenesis gen markers. CONCLUSION: This study indicated that on using the MF platform in preparation of DPs and loading them along with HA in PLLA/PEO scaffold, the osteogenic differentiation of hASCs could be tuned.

Gold-capped mesoporous silica nanoparticles as an excellent enzyme-responsive nanocarrier for controlled doxorubicin delivery.

Mesoporous silica nanoparticles (MSNs) have ideal characteristics as next generation of controlled drug delivery systems. In this study, a MSN-based nanocarrier was fabricated and gold nanoparticle (GNP)-biotin conjugates were successfully grafted onto the pore outlets of the prepared MSN. This bioconjugate served as a capping agent with a peptide-cleavable linker sensitive to matrix metalloproteinases (MMPs), which are overexpressed extracellular proteolytic enzymes in cancerous tissue. The prepared nanocarriers were fully characterised by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption, Fourier transform infra-red spectroscopy (FTIR), dynamic light scattering (DLS) and thermo gravimetric analysis (TGA). In vitro release studies showed efficient capping of MSNs with gold gate and controlled release of Doxorubicin (DOX) in the presence of matrix metalloproteinase-2 (MMP-2) and acidic pH values. High DOX-loading capacity (21%) and encapsulation efficiency (95.5%) were achieved using fluorescence technique. DOX-loaded nanocarriers showed high cytocompatibility and could efficiently induce cell death and apoptosis in the MMP-2 overexpressed cell lines. Moreover, Haemolysis, platelet activation and inflammatory responses assessment approved excellent hemocompatibility and minimal side effects by encapsulation of DOX in MSNs carrier.

Poly-l-lactic acid scaffold incorporated chitosan-coated mesoporous silica nanoparticles as pH-sensitive composite for enhanced osteogenic differentiation of human adipose tissue stem cells by dexamethasone delivery.

Nowadays, the development of drug-loaded electrospun organic-inorganic composite scaffolds for tissue engineering application is an attractive approach. In this study, a composite scaffold of Poly-l-lactic acid (PLLA) incorporated dexamethasone (Dexa) loaded Mesoporous Silica Nanoparticles (MSN) coated with Chitosan (CS) were fabricated by electrospinning for bone tissue engineering application. The MSN was prepared by precipitation method. After that, Dexamethasone (Dexa) was loaded into MSNs (MSN-Dexa). In the following, CS was coated over the prepared nanoparticles to form MSN-Dexa@CS and then, were mixed to PLLA solution to form MSN-Dexa@CS/PLLA composite for electrospinning. The surface morphology, hydrophilicity, tensile strength and the bioactivity of the scaffolds were characterized. The osteogenic proliferation and differentiation potential were evaluated by MTT assay and by measuring the basic osteogenic markers: the activity of the enzyme alkaline phosphatase and the level of calcium deposition. The composite scaffolds prepared here have conductive surface property and have a better osteogenic potential than pure PLLA scaffolds. Hence, the controlled release of nanoparticle containing Dexa from composite scaffold supported the osteogenesis and made the composite scaffolds ideal candidates for bone tissue engineering application and pH-sensitive delivery of drugs at the site of implantation in tissue regeneration.