A simplified framework for prediction of sensor network coverage in real-time structural health monitoring of plate-like structures

In this article, the coverage area prediction of piezoelectric sensor network for detecting a specific type of under-surface crack in plate-like structures is addressed. In particular, this article proposes a simplified framework to estimate the coverage of any given sensor network arrangement when a critical defect is known. Based on numerical results from finite element methods (FEM), a simplified framework to estimate coverage area of any given network arrangement is developed. Using such a simplified framework, one can avoid time-consuming procedure of evaluating numerous FEM models in estimating sensor network coverage. Back-scatter fields of partial cracks are estimated using a proposed function, whose parameters are estimated from the results of a limited number of FEM simulations. The proposed function efficiently predicts the back-scattered field of any combination of transmitters and receivers for a given crack geometry. Superposition is used to estimate the coverage area of an arbitrary piezoelectric (e.g., PZT) sensor network. It is shown that the coverage area of a sensor network depends on both sensor network geometry and defect properties (e.g., crack inclination) and it is not necessarily a linear function of the number of sensors. Furthermore, it is shown that the network arrangement has an important effect on the geometry of the coverage area. Experimental results of a network of 14 PZTs in two clusters confirm the accuracy of the method.

Modified Hyaluronic Acid-Laminin-Hydrogel as Luminal Filler for Clinically Approved Hollow Nerve Guides in a Rat Critical Defect Size Model

Hollow nerve guidance conduits are approved for clinical use for defect lengths of up to 3 cm. This is because also in pre-clinical evaluation they are less effective in the support of nerve regeneration over critical defect lengths. Hydrogel luminal fillers are thought to improve the regeneration outcome by providing an optimized matrix inside bioartificial nerve grafts. We evaluated here a modified hyaluronic acid-laminin-hydrogel (M-HAL) as luminal filler for two clinically approved hollow nerve guides. Collagen-based and chitosan-based nerve guides were filled with M-HAL in two different concentrations and the regeneration outcome comprehensively studied in the acute repair rat sciatic nerve 15 mm critical defect size model. Autologous nerve graft (ANG) repair served as gold-standard control. At 120 days post-surgery, all ANG rats demonstrated electrodiagnostically detectable motor recovery. Both concentrations of the hydrogel luminal filler induced improved regeneration outcome over empty nerve guides. However, neither combination with collagen- nor chitosan-based nerve guides resulted in functional recovery comparable to the ANG repair. In contrast to our previous studies, we demonstrate here that M-HAL slightly improved the overall performance of either empty nerve guide type in the critical defect size model.

Preparation of Poly Lactic-Co-Glycolic Acid-Based Implant Biomaterials and Its Adoption in Restoration of Periodontal Missing Teeth

As a commonly used macrolide antibiotic, azithromycin (AZM) has achieved favorable results in the treatment of periodontitis. However, due to the complex environment of the oral cavity, the time of action of topical medication is limited. In this study, AZM-poly lactic-co-glycolic acid (PLGA) microspheres were prepared by the emulsion-solvent evaporation method, whose morphology was observed by scanning electron microscopy. The AZM-PLGA microspheres of different specifications were obtained by using a paddle agitator and a homogenizing agitator, respectively. For the above two different specifications of AZM-PLGA microspheres, the mass ratios of AZM and PLGA were adjusted to 10:100, 15:100, 20:100, and 30:100, respectively. After the mechanical analysis of the microspheres, the slurry-type AZM-PLGA microspheres were taken as the positive control, and the critical defect model of alveolar bone was implanted in New Zealand white rabbits. Then, CT imaging of alveolar bone tissue was obtained at different time points after surgery. Plasma microspheres (20:100) were selected as the implant materials for the restoration of missing teeth in patients with periodontitis. After the test, the results showed that the AZM-PLGA microspheres obtained by the paddle agitator had relatively smaller particle size and smoother surface. The initial release rate of slurry microspheres of different quality was relatively fast, the follow-up rate was relatively stable, and the dosage ratio should not be more than 20%. Slurry microspheres had stronger mechanical properties compared with homogenized microspheres. The osteogenesis observation residues of slurry microspheres with different mass ratios were 15%, 23%, 37%, and 26% at 2–16 weeks, respectively, showing a relatively stable degradation mode. After the five patients with periodontitis participated in the restoration with the use of plasma microspheres (20:100) implants, the periodontal condition was greatly improved. During the observation period, all implants were not loosened and there was no discomfort during percussion.

A trimeric Rab7 GEF controls NPC1-dependent lysosomal cholesterol export

Cholesterol import in mammalian cells is mediated by the LDL receptor pathway. Here, we perform a genome-wide CRISPR screen using an endogenous cholesterol reporter and identify >100 genes involved in LDL-cholesterol import. We characterise C18orf8 as a core subunit of the mammalian Mon1-Ccz1 guanidine exchange factor (GEF) for Rab7, required for complex stability and function. C18orf8-deficient cells lack Rab7 activation and show severe defects in late endosome morphology and endosomal LDL trafficking, resulting in cellular cholesterol deficiency. Unexpectedly, free cholesterol accumulates within swollen lysosomes, suggesting a critical defect in lysosomal cholesterol export. We find that active Rab7 interacts with the NPC1 cholesterol transporter and licenses lysosomal cholesterol export. This process is abolished in C18orf8-, Ccz1- and Mon1A/B-deficient cells and restored by a constitutively active Rab7. The trimeric Mon1-Ccz1-C18orf8 (MCC) GEF therefore plays a central role in cellular cholesterol homeostasis coordinating Rab7 activation, endosomal LDL trafficking and NPC1-dependent lysosomal cholesterol export.

A facile one-stage treatment of critical bone defects using a calcium sulfate/hydroxyapatite biomaterial providing spatiotemporal delivery of bone morphogenic protein–2 and zoledronic acid

Bone morphogenic proteins (BMPs) are the only true osteoinductive molecules. Despite being tremendously potent, their clinical use has been limited for reasons including supraphysiological doses, suboptimal delivery systems, and the pro-osteoclast effect of BMPs. Efforts to achieve spatially controlled bone formation using BMPs are being made. We demonstrate that a carrier consisting of a powder of calcium sulfate/hydroxyapatite (CaS/HA) mixed with bone active molecules provides an efficient drug delivery platform for critical femoral defect healing in rats. The bone-active molecules were composed of osteoinductive rhBMP-2 and the bisphosphonate, and zoledronic acid (ZA) was chosen to overcome BMP-2–induced bone resorption. It was demonstrated that delivery of rhBMP-2 was necessary for critical defect healing and restoration of mechanical properties, but codelivery of BMP-2 and ZA led to denser and stronger fracture calluses. Together, the CaS/HA biomaterial with rhBMP-2 and/or ZA can potentially be used as an off-the-shelf alternative to autograft bone.

3D Biomimetic Porous Titanium (Ti6Al4V ELI) Scaffolds for Large Bone Critical Defect Reconstruction: An Experimental Study in Sheep

The main goal in the treatment of large bone defects is to guarantee a rapid loading of the affected limb. In this paper, the authors proposed a new reconstructive technique that proved to be suitable to reach this purpose through the use of a custom-made biomimetic porous titanium scaffold. An in vivo study was undertaken where a complete critical defect was experimentally created in the diaphysis of the right tibia of twelve sheep and replaced with a five-centimeter porous scaffold of electron beam melting (EBM)-sintered titanium alloy (EBM group n = 6) or a porous hydroxyapatite scaffold (CONTROL group, n = 6). After surgery, the sheep were allowed to move freely in the barns. The outcome was monitored for up to 12 months by periodical X-ray and clinical examination. All animals in the CONTROL group were euthanized for humane reasons within the first month after surgery due to the onset of plate bending due to mechanical overload. Nine months after surgery, X-ray imaging showed the complete integration of the titanium implant in the tibia diaphysis and remodeling of the periosteal callus, with a well-defined cortical bone. At 12 months, sheep were euthanized, and the tibia were harvested and subjected to histological analysis. This showed bone tissue formations with bone trabeculae bridging titanium trabeculae, evidencing an optimal tissue-metal interaction. Our results show that EBM-sintered titanium devices, if used to repair critical bone defects in a large animal model, can guarantee immediate body weight-bearing, a rapid functional recovery, and a good osseointegration. The porous hydroxyapatite scaffolds proved to be not suitable in this model of large bone defect due to their known poor mechanical properties.