There is an increasing demand for an injectable cell coupled three-dimensional (3D) scaffold to be used as bone fracture augmentation material. To address this demand, a novel injectable osteogenic scaffold called PN-COL was developed using cells, a natural polymer (collagen type-I), and a synthetic polymer (polycaprolactone (PCL)). The injectable nanofibrous PN-COL is created by interspersing PCL nanofibers within pre-osteoblast cell embedded collagen type-I. This simple yet novel and powerful approach provides a great benefit as an injectable bone scaffold over other non-living bone fracture stabilization polymers, such as polymethylmethacrylate and calcium content resin-based materials. The advantages of injectability and the biomimicry of collagen was coupled with the structural support of PCL nanofibers, to create cell encapsulated injectable 3D bone scaffolds with intricate porous internal architecture and high osteoconductivity. The effects of PCL nanofiber inclusion within the cell encapsulated collagen matrix has been evaluated for scaffold size retention and osteocompatibility, as well as for MC3T3-E1 cells osteogenic activity. The structural analysis of novel bioactive material proved that the material is chemically stable enough in an aqueous solution for an extended period of time without using crosslinking reagents, but it is also viscous enough to be injected through a syringe needle. Data from long-term in vitro proliferation and differentiation data suggests that novel PN-COL scaffolds promote the osteoblast proliferation, phenotype expression, and formation of mineralized matrix. This study demonstrates for the first time the feasibility of creating a structurally competent, injectable, cell embedded bone tissue scaffold. Furthermore, the results demonstrate the advantages of mimicking the hierarchical architecture of native bone with nano- and micro-size formation through introducing PCL nanofibers within macron-size collagen fibers and in promoting osteoblast phenotype progression for bone regeneration.

Smoking has long been associated with osteoporosis, decreased bone mineral density, increased risk of bone fracture, and increased health costs. Nicotine, the main component of cigarette smoke, has major negative effects on bone metabolism and skeletal remodeling in vivo. Although osteoblasts and osteoblast-like cells have been used extensively to study the impact of nicotine, few studies have been performed on human mesenchymal stem cells (hMSCs). In this context, we examined the impact of nicotine on (a) hMSCs proliferation, (b) osteoblastic differentiation, (c) alkaline phosphatase (ALP) activity, and (d) expression of canonical genes during differentiation of hMSCs. MSCs isolated from human bone marrow were treated with different concentrations (0, 0.1, 1 and 10 μM) of nicotine for 7 days. Nicotine caused a dose-dependent decrease in cell proliferation, decreased heme oxygenase-1 (HO-1) expression (p < 0.05) and attenuated osteogenesis (p < 0.05) in hMSCs (45 % reduction at day 14). In addition, nicotine caused a dose-dependent decrease in alizarin red staining for calcium and staining for ALP. Induction of HO-1 by peroxisome proliferator-activated receptor delta agonist (GW0742) prevented the effect of nicotine. Nicotine caused a dose-dependent reduction in the expression of BMP-2, a well-known marker for bone formation; however, this was prevented by GW0742 treatment. Therefore, induction of HO-1 prevents the deleterious effects of nicotine on osteogenesis in hMSC. This offers insight into both how nicotine affects bone remodeling and a therapeutic approach to prevent fracture and osteoporosis in smokers.

X-ray topography investigations of dislocations generated by compression of InSb and by microindentation of InSb and GaAs si!:!g!e crystals revealed that dislocations glide parallel to the (lll) surface and react in the (111) plane. The present paper proposes possible explanation of reaction between c.lislocations belonging to two neighboming wings (fig.l). For the node I reaction resulting in junction fmmation leeds to Lomer-Cottrell