Various strategies have been explored to overcome critically sized bone defects via bone tissue engineering approaches that incorporate biomimetic scaffolds. Biomimetic scaffolds may provide a novel platform for phenotypically stable tissue formation and stem cell differentiation. In recent years, osteoinductive and inorganic biomimetic scaffold materials have been optimized to offer an osteo-friendly microenvironment for the osteogenic commitment of stem cells. Furthermore, scaffold structures with a microarchitecture design similar to native bone tissue are necessary for successful bone tissue regeneration. For this reason, various methods for fabricating 3D porous structures have been developed. Innovative techniques, such as 3D printing methods, are currently being utilized for optimal host stem cell infiltration, vascularization, nutrient transfer, and stem cell differentiation. In this progress report, biomimetic materials and fabrication approaches that are currently being utilized for biomimetic scaffold design are reviewed.
In this work, we developed biodegradable chitin nanogels (CNGs) by controlled regeneration method. For multifunctionalization, we have conjugated CNGs with MPA-capped-CdTe-QDs (QD-CNGs) for the in vitro cellular localization studies. In addition, the Bovine Serum Albumin (BSA) was loaded on to QD-CNGs (BSA-QD-CNGs). The CNGs, QD-CNGs, and BSA-QD-CNGs were well-characterized by SEM and AFM, which shows that the nanogels are in the range of <100 nm. These were further characterized by FT-IR and Cyclic Voltametry. The cytocompatibility assay showed that the nanogels are nontoxic to L929, NIH-3T3, KB, MCF-7, PC3, and VERO cells. The cell uptake studies of the QD-CNGs were analyzed, which showed retention of these nanogels inside the cells (L929, PC3, and VERO). In addition, the protein loading efficiency of the nano gels has also been analyzed. Our preliminary studies reveal that these multifunctionalized nanogels could be useful for drug delivery with simultaneous imaging and biosensing.
Poly(caprolactone) (PCL) has been frequently considered for bone tissue engineering because of its excellent biocompatibility. A drawback, however, of PCL is its inadequate mechanical strength for bone tissue engineering and its inadequate bioactivity to promote bone tissue regeneration from mesenchymal stem cells. To correct this deficiency, this work investigates the addition of nanoparticles of silica (nSiO(2)) to the scaffold to take advantage of the known bioactivity of silica as an osteogenic material and also to improve the mechanical properties through nanoscale reinforcement of the PCL fibers. The nanocomposite scaffolds and the pristine PCL scaffolds were evaluated physicochemically, mechanically, and biologically in the presence of human mesenchymal stem cells (hMSCs). The results indicated that, when the nanoparticles of size approximately 10 nm (concentrations of 0.5% and 1% w/v) were embedded within, or attached to, the PCL nanofibers, there was a substantial increase in scaffold strength, protein adsorption, and osteogenic differentiation of hMSCs. These nSiO(2) nanoparticles, when directly added to the cells evidently pointed to ingestion of these particles by the cells followed by cell death. The polymer nanofibers appeared to protect the cells by preventing ingestion of the silica nanoparticles, while at the same time adequately exposing them on fiber surfaces for their desired bioactivity.
Uncontrolled bleeding can lead to many complications that might cause multiple organ failures and even death. Of all the hemostatic agents used, chitosan has been reported to show better hemostatic potential. It acts through one mechanism involved in hemostasis that is plug formation by adhering to the injured site. Hence our focus is to enhance the hemostatic potential of chitosan (Ch) hydrogel by incorporating nano whitlockite (nWH: Ca18Mg2(HPO4)2(PO4)12) that would release Ca2+, Mg2+, and PO4 3– ions that would simultaneously initiate the coagulation cascade. Ch-nWH composite hydrogel can act simultaneously on different mechanisms involved in hemostasis and bring about rapid bleeding control. The nWH particles were synthesized using precipitation technique and were characterized. Particle size of nWH was found to be 75 ± 5 nm. Composite hydrogel was characterized using FTIR and XRD to confirm the presence of different constituents of the hydrogel. Rheological studies showed the shear-thinning property and increased elastic modulus of the composite hydrogel compared to Ch hydrogel. 2%Ch-4%nWH hydrogel was observed to be cytocompatible with Human Umbilical Vein Endothelial Cells (HUVEC). In the in vitro blood clotting analysis using citrated human whole blood, 2%Ch-4%nWH hydrogel showed rapid blood clot formation compared to control 2%Ch hydrogel. Further in vivo experiments performed on liver and femoral artery injuries created on Sprague–Dawley (S.D) rat model reveals that 2%Ch-4%nWH hydrogel promoted rapid bleeding control and less volume of blood loss compared to Ch hydrogel. These in vitro and in vivo results showed that incorporation of nWH has enhanced the hemostatic potential of Ch hydrogel. Therefore, the synthesized 2%Ch-4%nWH hydrogel may be a promising system that could bring about rapid hemostasis during life threatening bleeding.
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