SummaryAging is a major risk factor for tendon injury and impaired tendon healing, but the basis for these relationships remains poorly understood. Here we show that rat tendon-derived stem ⁄ progenitor cells (TSPCs) differ in both self-renewal and differentiation capability with age. The frequency of TSPCs in tendon tissues of aged animals is markedly reduced based on colony formation assays. Proliferation rate is decreased, cell cycle progression is delayed and cell fate patterns are also altered in aged TSPCs. In particular, expression of tendon lineage marker genes is reduced while adipocytic differentiation increased. Cited2, a multi-stimuli responsive transactivator involved in cell growth and senescence, is also downregulated in aged TSPCs while CD44, a matrix assembling and organizing protein implicated in tendon healing, is upregulated, suggesting that these genes participate in the control of TSPC function.

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.

Visual force feedback resulted in reduced suture breakage, lower forces, and decreased force inconsistencies among novice robotic surgeons, although elapsed time and knot quality were unaffected. In contrast, visual force feedback did not affect these metrics among surgeons experienced with the da Vinci system. These results suggest that visual force feedback primarily benefits novice robot-assisted surgeons, with diminishing benefits among experienced surgeons.

Mesenchymal stem cells (MSCs) are pluripotent cells that primarily differentiate into osteocytes, chondrocytes, and adipocytes. Recent studies indicate that MSCs can also be induced to generate tenocyte-like cells; moreover, MSCs have been suggested to have great therapeutic potential for tendon pathologies. Yet the precise molecular cascades governing tenogenic differentiation of MSCs remain unclear. We demonstrate scleraxis, a transcription factor critically involved in embryonic tendon development and formation, plays a pivotal role in the fate determination of MSC towards tenocyte differentiation. Using murine C3H10T1/2 pluripotent stem cells as a model system, we show scleraxis is extensively expressed in the early phase of bone morphogenetic protein (BMP)-12-triggered tenocytic differentiation. Once induced, scleraxis directly transactivates tendon lineage-related genes such as tenomodulin and suppresses osteogenic, chondrogenic, and adipogenic capabilities, thus committing C3H10T1/2 cells to differentiate into the specific tenocyte-like lineage, while eliminating plasticity for other lineages. We also reveal that mechanical loading-mediated tenocytic differentiation follows a similar pathway and that BMP-12 and cyclic uniaxial strain act in an additive fashion to augment the maximal response by activating signal transducer Smad8. These results provide critical insights into the determination of multipotent stem cells to the tenocyte lineage induced by both chemical and physical signals.

Summary: Facial rejuvenation is a rapidly advancing field in aesthetic medicine. Minimally invasive techniques represent a powerful tool for rejuvenation, and fillers are a popular modality with which to restore and optimize facial proportions. Currently, our filler armamentarium is characterized by products with an increasing variety of biochemical compositions warranting tailored injection approaches. An intimate knowledge of anatomy, product characteristics, and appropriate injection techniques is essential to achieve optimal results while maintaining patient safety. Here, we review facial anatomy, structural changes secondary to aging, appropriate filler selection, safe injection techniques, and complications.

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Teleoperated robot-assisted surgical systems provide surgeons with improved precision, dexterity, and visualization over traditional minimally invasive surgery. The addition of haptic (force and/or tactile) feedback has been proposed as a way to further enhance the performance of these systems. However, due to limitations in sensing and control technologies, implementing direct haptic feedback to the surgeon's hands remains impractical for clinical application. A new, intuitive augmented reality system for presentation of force information through sensory substitution has been developed and evaluated. The augmented reality system consists of force-sensing robotic instruments, a kinematic tool tracker, and a graphic display that overlays a visual representation of force levels on top of the moving instrument tips. The system is integrated with the da Vinci Surgical System (Intuitive Surgical, Inc.) and tested by several users in a phantom knot tying task. The augmented reality system decreases the number of broken sutures, decreases the number of loose knots, and results in more consistent application of forces.

There is a lack of comprehensive, valid, and reliable questionnaires for cleft lip and palate surgery. For thorough assessment of satisfaction, further research to develop and validate cleft lip and palate surgery-specific instruments is needed.