The objective of the present investigation was to assess the potential of magnesium oxide nanoparticle (MgO NP)-loaded electrospun polycaprolactone (PCL) polymer composites as a bone-soft tissue engineering scaffold. MgO NPs were synthesized using a hydroxide precipitation sol-gel method and characterized using field emission gun-scanning electron microscopy/energy-dispersive x-ray spectroscopy (FEG-SEM/EDS), field emission gun-transmission electron microscopy (FEG-TEM), and x-ray diffraction (XRD) analysis. PCL and MgO-PCL nanocomposite fibers were fabricated using electrospinning with trifluoroethanol as solvent at 19 kV applied voltage and 1.9 ml h flow rate as optimized process parameters, and were characterized by FEG-TEM, FEG-SEM/EDS, XRD, and differential scanning calorimetry analyses. Characterization studies of as-synthesized nanoparticles revealed diffraction peaks indexed to various crystalline planes peculiar to MgO particles with hexagonal and cubical shape, and 40-60 nm size range. Significant improvement in mechanical properties (tensile strength and elastic modulus) of nanocomposites was observed as compared to neat polymer specimens (fourfold and threefold, respectively), due to uniform dispersion of nanofillers along the polymer fiber length. There was a remarkable bioactivity shown by nanocomposite scaffolds in immersion test, as indicated by formation of surface hydroxyapatite layer by the third day of incubation. MgO-loaded electrospun PCL mats showed enhanced in-vitro biological performance with osteoblast-like MG-63 cells in terms of adhesion, proliferation, and marked differentiation marker activity owing to greater surface roughness, nanotopography, and hydrophilicity facilitating higher protein adsorption. In-vivo subcutaneous implantation study in Sprague Dawley rats revealed initial moderate inflammatory tissue response near implant site at the second week timepoint that subsided later (eighth week) with no adverse effect on vital organ functionalities as seen in histopathological analysis supported by serum biochemical and hematological parameters which did not deviate significantly from normal physiological range, indicating good biocompatibility in-vivo. Thus, MgO-PCL nanocomposite electrospun fibers have potential as an efficient scaffold material for bone-soft tissue engineering applications.
Hydrogels formed by the self-assembly of low-molecular-weight gelators (LMWGs) are promising scaffolds for drug-delivery applications. A new biocompatible hydrogel, resulting from the self-assembly of nucleotide-lipid salts can be safely injected in vivo. The resulting hydrogel provides sustained-release of protein for more than a week.
Bone morphogenetic protein 2 (BMP-2) is a potent inducer of bone formation that is currently used in a limited number of clinical indications to treat extensive bone loss. Extending the field of applications of this molecule requires design of the delivery system to protect the protein from early degradation and allow a slow long-term release. This study describes the use of a non-polymer hydrogel, based on the self-assembly of small amphiphilic glycosyl-nucleolipids into micellar structures, as a new type of delivery system for BMP-2. BMP-2 was readily encapsulated in glycosyl-nucleosyl-fluorinated (GNF)-based gels and slowly released in vitro, while maintaining its osteogenic activity. When hydrogel pieces containing fluorophore-tagged BMP-2 were deposited onto a calvaria defect in mouse, the signal detected in living mice gradually decreased and was still detectable at 3 weeks. Gel-embedded protein promoted significant calvarial bone defect regeneration at 8 weeks after surgery. In contrast, when a solution of BMP-2 without hydrogel was injected into the defects, the fluorescence signal decreased rapidly and no significant bone formation was observed. The unique property of the GNF-based hydrogel as an injectable delivery system for low doses of BMP-2 was revealed in a subcutaneous model of ectopic bone formation. Injected BMP-2-laden GNF hydrogel blocks elicited the formation of cancellous bone, showing all the typical features of remodeling bone that contains bone marrow. These results show that this GNF-based hydrogel is an easy-to-use, efficient delivery system for BMP-2 and osteogenic material to support bone regeneration.
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