A xonotlite nanofiber bioactive 3D-printed hydrogel scaffold based on osteo-/angiogenesis and osteoimmune microenvironment remodeling accelerates vascularized bone regeneration.

BACKGROUND: Coordination between osteo-/angiogenesis and the osteoimmune microenvironment is essential for effective bone repair with biomaterials. As a highly personalized and precise biomaterial suitable for repairing complex bone defects in clinical practice, it is essential to endow 3D-printed scaffold the above key capabilities. RESULTS: Herein, by introducing xonotlite nanofiber (Ca6(Si6O17) (OH)2, CS) into the 3D-printed silk fibroin/gelatin basal scaffold, a novel bone repair system named SGC was fabricated. It was noted that the incorporation of CS could greatly enhance the chemical and mechanical properties of the scaffold to match the needs of bone regeneration. Besides, benefiting from the addition of CS, SGC scaffolds could accelerate osteo-/angiogenic differentiation of bone mesenchymal stem cells (BMSCs) and meanwhile reprogram macrophages to establish a favorable osteoimmune microenvironment. In vivo experiments further demonstrated that SGC scaffolds could efficiently stimulate bone repair and create a regeneration-friendly osteoimmune microenvironment. Mechanistically, we discovered that SGC scaffolds may achieve immune reprogramming in macrophages through a decrease in the expression of Smad6 and Smad7, both of which participate in the transforming growth factor-ß (TGF-ß) signaling pathway. CONCLUSION: Overall, this study demonstrated the clinical potential of the SGC scaffold due to its favorable pro-osteo-/angiogenic and osteoimmunomodulatory properties. In addition, it is a promising strategy to develop novel bone repair biomaterials by taking osteoinduction and osteoimmune microenvironment remodeling functions into account.

Automating the Human Action of First-Trimester Biometry Measurement from Real-World Freehand Ultrasound.

OBJECTIVE: Automated medical image analysis solutions should closely mimic complete human actions to be useful in clinical practice. However, more often an automated image analysis solution represents only part of a human task, which restricts its practical utility. In the case of ultrasound-based fetal biometry, an automated solution should ideally recognize key fetal structures in freehand video guidance, select a standard plane from a video stream and perform biometry. A complete automated solution should automate all three subactions. METHODS: In this article, we consider how to automate the complete human action of first-trimester biometry measurement from real-world freehand ultrasound. In the proposed hybrid convolutional neural network (CNN) architecture design, a classification regression-based guidance model detects and tracks fetal anatomical structures (using visual cues) in the ultrasound video. Several high-quality standard planes that contain the mid-sagittal view of the fetus are sampled at multiple time stamps (using a custom-designed confident-frame detector) based on the estimated probability values associated with predicted anatomical structures that define the biometry plane. Automated semantic segmentation is performed on the selected frames to extract fetal anatomical landmarks. A crown-rump length (CRL) estimate is calculated as the mean CRL from these multiple frames. RESULTS: Our fully automated method has a high correlation with clinical expert CRL measurement (Pearson's p = 0.92, R-squared [R2] = 0.84) and a low mean absolute error of 0.834 (weeks) for fetal age estimation on a test data set of 42 videos. CONCLUSION: A novel algorithm for standard plane detection employs a quality detection mechanism defined by clinical standards, ensuring precise biometric measurements.

BMSCs-laden mechanically reinforced bioactive sodium alginate composite hydrogel microspheres for minimally invasive bone repair.

Minimally invasive, efficient, and satisfactory treatment for irregular and lacunar bone defects is still a challenge. Alginate hydrogels serve as promising stem cell (SC) delivery systems for bone regeneration but are limited by low cellular viability, poor osteogenic differentiation, and insufficient mechanical support. Herein, we developed a BMSCs-laden mechanically reinforced bioactive sodium alginate composite hydrogel microspheres (BCHMs) system via a microfluidic method that possesses 1) a uniform size and good injectability to meet clinical bone defects with complex shapes, 2) high cellular viability maintenance and further osteogenic induction capacity, and 3) improved mechanical properties. As the main matrix, the sodium alginate hydrogel maintains the high viability of encapsulated BMSCs and efficient substance exchange. Enhanced mechanical properties and osteogenic differentiation of the BCHMs in vitro were observed with xonotlite (Ca6Si6O17(OH)2, CSH) nanowires incorporated. Furthermore, BCHMs with 12.5 % CSH were injected into rat femoral bone defects, and satisfactory in situ regeneration outcomes were observed. Overall, it is believed that BCHMs expand the application of polysaccharide science and provide a promising injectable bone substitute for minimally invasive bone repair.

A multifunctional quercetin/polycaprolactone electrospun fibrous membrane for periodontal bone regeneration.

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