Bone Tumor Suppression in Rabbits by Hyperthermia below the Clinical Safety Limit Using Aligned Magnetic Bone Cement.

Demonstrating highly efficient alternating current (AC) magnetic field heating of nanoparticles in physiological environments under clinically safe field parameters has remained a great challenge, hindering clinical applications of magnetic hyperthermia. In this work, exceptionally high loss power of magnetic bone cement under the clinical safety limit of AC field parameters, incorporating direct current field-aligned soft magnetic Zn0.3 Fe2.7 O4 nanoparticles with low concentration, is reported. Under an AC field of 4 kA m-1 at 430 kHz, the aligned bone cement with 0.2 wt% nanoparticles achieves a temperature increase of 30 °C in 180 s. This amounts to a specific loss power value of 327 W gmetal-1 and an intrinsic loss power of 47 nHm2 kg-1 , which is enhanced by 50-fold compared to randomly oriented samples. The high-performance magnetic bone cement allows for the demonstration of effective hyperthermia suppression of tumor growth in the bone marrow cavity of New Zealand White Rabbits subjected to rapid cooling due to blood circulation, and significant enhancement of survival rate.

Osteocytogenesis: Roles of Physicochemical Factors, Collagen Cleavage, and Exogenous Molecules.

Osteocytes, the most abundant cell type in mammalian bone, are generally considered as the terminally differentiated cells of osteoblasts that are progressively self-buried or passively embedded in bone matrix. Emerging evidence reveals the essential functions of osteocytes in bone homeostasis and mechanotransduction. However, our knowledge on osteocytes, especially their formation, remains scarce. In this regard, the current review mainly focuses on several key factors that drive the osteocytic differentiation of osteoblasts, that is, osteocytogenesis. Available literature has demonstrated the involvement of physicochemical factors such as matrix composition, oxygen tension, and mechanical stress in the osteoblast-to-osteocyte transition. During cell migration and matrix remodeling, the matrix metalloproteinase-dependent collagen cleavage would play an "active" role in maturation and maintenance of the osteocytes. Besides, some in vitro methodologies are also established to induce the transformation of osteoblastic cell lines and primary mesenchymal cells to preosteocytes through cell transfection or addition of exogenous molecules (e.g., fibroblast growth factor-2, retinoic acid), which could potentiate the effort to form functional bone substitutes through elevated osteocytogenesis. Thus, advances of new technologies would enable comprehensive and in-depth understanding of osteocytes and their development, which in turn help promote the research on osteocyte biology and osteopathology.

Improved cell infiltration of electrospun nanofiber mats for layered tissue constructs.

While achieving the spatial organization of cells within 3D assembled nanofiber/cell constructs via nanofiber-enabled cell layering, the small sizes of inter-fiber pores of the electrospun nanofiber mats could significantly limit cell penetration across the layers for rapid formation of an integrated tissue construct. To address this challenge, efforts were made to improve cell-infiltration of electrospun nanofiber mats by modulating the density distribution and spatial organization of the fibers during electrospinning. Collection of collagen-containing electrospun nanofibers (300-600 nm in diameter) onto the surface of a stainless steel metal mesh (1 mm × 1 mm in mesh size) led to the periodic alternation of fiber density from densely packed to loosely arranged distribution within the same mat, in which the densely packed fibers maintained the structural integrity while the region of loose fibers allowed for cell penetration. Along with improved cell infiltration, the distinct fiber organization between dense and loose fiber regions also induced different morphology of fibroblasts (stellate vs. elongated spindle-like). Assembly of cell-seeded nanofiber sheets into 3D constructs with such periodically organized nanofiber mats further demonstrated their advantages in improving cell penetration across layers in comparison to either random or aligned nanofiber mats. Taken together, modulation of nanofiber density to enlarge the pore size is effective to improve cell infiltration through electrospun mats for better tissue formation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1479-1488, 2016.