We characterized the differentiation of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) into tenocyte-like cells in response to bone morphogenetic protein-12 (BMP-12). BM-MSCs were prepared from Sprague-Dawley rats and cultured as monolayers. Recombinant BMP-12 treatment (10 ng/ml) of BM-MSCs for 12 hours in vitro markedly increased expression of the tenocyte lineage markers scleraxis (Scx) and tenomodulin (Tnmd) over 14 days. Treatment with BMP-12 for a further 12-hour period had no additional effect. Colony formation assays revealed that ∼80% of treated cells and their progeny were Scx- and Tnmd-positive. BM-MSCs seeded in collagen scaffolds and similarly treated with a single dose of BMP-12 also expressed high levels of Scx and Tnmd, as well as type I collagen and tenascin-c. Furthermore, when the treated BM-MSC-seeded scaffolds were implanted into surgically created tendon defects in vivo, robust formation of tendon-like tissue was observed after 21 days as evidenced by increased cell number, elongation and alignment along the tensile axis, greater matrix deposition and the elevated expression of tendon markers. These results indicate that brief stimulation with BMP-12 in vitro is sufficient to induce BM-MSC differentiation into tenocytes, and that this phenotype is sustained in vivo. This strategy of pretreating BM-MSCs with BMP-12 prior to in vivo transplantation may be useful in MSC-based tendon reconstruction or tissue engineering.

We demonstrate a silicon carbide (SiC) microdisk resonator with optical Q up to 5.12 × 104. The high optical quality, together with the diversity of whispering-gallery modes and the tunability of external coupling, renders SiC microdisk a promising platform for integrated quantum photonics applications.

Both underloading and overloading of joints can lead to articular cartilage degradation, a process mediated in part by matrix metalloproteinases (MMPs). Here we examine the effects of reduced loading of rat hindlimbs on articular cartilage expression of MMP-3, which not only digests matrix components but also activates other proteolytic enzymes. We show that hindlimb immobilization resulted in elevated MMP-3 mRNA expression at 6 hours that was sustained throughout the 21 day immobilization period. MMP-3 upregulation was higher in the medial condyle than the lateral, and was greatest in the superficial cartilage zone, followed by middle and deep zones. These areas also showed decreases in safranin O staining, consistent with reduced cartilage proteoglycan content, as early as 7 days after immobilization. One hour of daily moderate mechanical loading, applied as passive joint motion, reduced the MMP-3 and ADAMTS-5 increases that resulted from immobilization, and also prevented changes in safranin O staining. Intra-articular injections of an MMP-3 inhibitor, N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid (NNGH), dampened the catabolic effects of a 7 day immobilization period, indicating a likely requirement for MMP-3 in the regulation of proteoglycan levels through ADAMTS-5. These results suggest that biomechanical forces have the potential to combat cartilage destruction and can be critical in developing effective therapeutic strategies.

The quest for realizing and manipulating ever smaller man-made movable structures and dynamical machines has spurred tremendous endeavors, led to important discoveries, and inspired researchers to venture to new grounds. Scientific feats and technological milestones of miniaturization of mechanical structures have been widely accomplished by advances in machining and sculpturing ever shrinking features out of bulk materials such as silicon. With the flourishing multidisciplinary field of low-dimensional nanomaterials, including onedimensional (1D) nanowires/nanotubes, and two-dimensional (2D) atomic layers such as graphene/phosphorene, growing interests and sustained efforts have been devoted to creating mechanical devices toward the ultimate limit of miniaturization-genuinely down to the molecular or even atomic scale. These ultrasmall movable structures, particularly nanomechanical resonators that exploit the vibratory motion in these 1D and 2D nano-toatomic-scale structures, offer exceptional device-level attributes, such as ultralow mass, ultrawide frequency tuning range, broad dynamic range, and ultralow power consumption, thus holding strong promises for both fundamental studies and engineering applications. In this Review, we offer a comprehensive overview and summary of this vibrant field, present the state-of-the-art devices and evaluate their specifications and performance, outline important achievements, and postulate future directions for studying these miniscule yet intriguing molecular-scale machines.

We demonstrate a high-Q amorphous silicon carbide (a-SiC) microresonator with optical Q as high as 1.3 × 10(5). The high optical quality allows us to characterize the third-order nonlinear susceptibility of a-SiC. The Kerr nonlinearity is measured to be n2 = (5.9 ± 0.7) × 10(−15) cm(2)/W in the telecom band around 1550 nm. The strong Kerr nonlinearity and high optical quality render a-SiC microresonators a promising platform for integrated nonlinear photonics.