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Macroporous scaffolds made of a SiO2-CaO-P2O5 mesoporous bioactive glass (MBG) and ɛ-polycaprolactone (PCL) have been prepared by robocasting. These scaffolds showed an excellent in ...vitro biocompatibility in contact with osteoblast like cells (Saos 2) and osteoclasts derived from RAW 264.7 macrophages. In vivo studies were carried out by implantation into cavitary defects drilled in osteoporotic sheep. The scaffolds evidenced excellent bone regeneration properties, promoting new bone formation at both the peripheral and the inner parts of the scaffolds, thick trabeculae, high vascularization and high presence of osteoblasts and osteoclasts. In order to evaluate the effects of the local release of an antiosteoporotic drug, 1% (%wt) of zoledronic acid was incorporated to the scaffolds. The scaffolds loaded with zoledronic acid induced apoptosis in Saos 2 cells, impeded osteoclast differentiation in a time dependent manner and inhibited bone healing, promoting an intense inflammatory response in osteoporotic sheep.
In addition to an increase in bone fragility and susceptibility to fracture, osteoporosis also hinders the clinical success of endosseous implants and grafting materials for the treatment of bone defects. For the first time, macroporous scaffolds made of mesoporous bioactive glass and ε-caprolactone have been evaluated in a sheep model that mimics the osteoporosis conditions in humans. These implants fostered bone regeneration, promoting new bone formation at both the peripheral and the inner parts of the scaffolds, showing thick trabeculae and a high vascularization degree. Our results indicate that macroporous structures containing highly bioactive mesoporous glasses could be excellent candidates for the regenerative treatment of bone defects in osteoporotic patients.
Macroporous scaffolds made of a SiO
2
-CaO-P
2
O
5
mesoporous bioactive glass (MBG) and ε-polycaprolactone (PCL) have been prepared by robocasting. These scaffolds showed an excellent
in vitro
...biocompatibility in contact with osteoblast like cells (Saos 2) and osteoclasts derived from RAW 264.7 macrophages.
In vivo
studies were carried out by implantation into cavitary defects drilled in osteoporotic sheep. The scaffolds evidenced excellent bone regeneration properties, promoting new bone formation at both the peripheral and the inner parts of the scaffolds, thick trabeculae, high vascularization and high presence of osteoblasts and osteoclasts. In order to evaluate the effects of the local release of an antiosteoporotic drug, 1% (%wt) of zoledronic acid was incorporated to the scaffolds. The scaffolds loaded with zoledronic acid induced apoptosis in Saos 2 cells, impeded osteoclast differentiation in a time dependent manner and inhibited bone healing, promoting an intense inflammatory response in osteoporotic sheep.
The Alzheimer's Association's Research Roundtable met in November 2017 to explore the new National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease. The ...meeting allowed experts in the field from academia, industry, and government to provide perspectives on the new National Institute on Aging and the Alzheimer's Association Research Framework. This review will summarize the “A, T, N System” (Amyloid, Tau, and Neurodegeneration) using biomarkers and how this may be applied to clinical research and drug development. In addition, challenges and barriers to the potential adoption of this new framework will be discussed. Finally, future directions for research will be proposed.
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The osteogenic and angiogenic responses to metal macroporous scaffolds coated with silicon substituted hydroxyapatite (SiHA) and decorated with vascular endothelial growth factor ...(VEGF) have been evaluated in vitro and in vivo. Ti6Al4V-ELI scaffolds were prepared by electron beam melting and subsequently coated with Ca10(PO4)5.6(SiO4)0.4(OH)1.6 following a dip coating method. In vitro studies demonstrated that SiHA stimulates the proliferation of MC3T3-E1 pre-osteoblastic cells, whereas the adsorption of VEGF stimulates the proliferation of EC2 mature endothelial cells. In vivo studies were carried out in an osteoporotic sheep model, evidencing that only the simultaneous presence of both components led to a significant increase of new tissue formation in osteoporotic bone.
Reconstruction of bones after severe trauma or tumors extirpation is one of the most challenging tasks in the field of orthopedic surgery. This scenario is even more complicated in the case of osteoporotic patients, since their bone regeneration capability is decreased. In this work we present a porous implant that promotes bone regeneration even in osteoporotic bone. By coating the implant with osteogenic bioceramics such as silicon substituted hydroxyapatite and subsequent adsorption of vascular endothelial growth factor, these implants stimulate the bone ingrowth when they are implanted in osteoporotic sheep.
Reconstructive and ablative urologic techniques require special technical mastery, especially the intracorporeal suturing.
To report the subjective evaluation of a versatile ex-vivo model aimed to ...practice laparoscopic ureteric reconstructive techniques (LURT) on box-trainer.
The model is a continuous portion of porcine urinary bladder (“dilated pelvis”), the vesico-ureteral joint (“stenosis”) and healthy ureter. All 127 participants (n = 119 urologists and n = 8 paediatric surgeons) performed on the model laparoscopic Anderson-Hynes dismembered pyeloplasty, and then, in the animal model, different LURT procedures (ureteroneocystostomy, ureteric reimplantation and/or dismembered pyeloplasty). The model was subjectively evaluated (face and content validity), through a 12 items questionnaire, based on a Likert scale (1–5 points) and a global question (1–10 points).
The total mean rating for 11/12 items was very high (>4points). Only one was rated under 3 points. The overall total mean rating from 1 to 10 points was very high (9.19 ± 0.82 points). In 10/12 items, expert's feedback (content validity) prevailed over non-experts (face validity).
The model was highly accepted for the practice of LURT techniques. Additionally, it is cost-effective, easy to assemble, ethically considerate, and realistic. Display omitted
The muon tagging is an essential tool to distinguish between gamma and hadron-induced showers in wide field-of-view gamma-ray observatories. In this work, it is shown that an efficient muon tagging ...(and counting) can be achieved using a water Cherenkov detector with a reduced water volume and 4 PMTs, provided that the PMT signal spatial and time patterns are interpreted by an analysis based on machine learning (ML). The developed analysis has been tested for different shower and array configurations. The output of the ML analysis, the probability of having a muon in the WCD station, has been used to notably discriminate between gamma and hadron induced showers with
S
/
B
∼
4
for shower with energies
E
0
∼
1
TeV. Finally, for proton-induced showers, an estimator of the number of muons was built by means of the sum of the probabilities of having a muon in the stations. Resolutions about
20
%
and a negligible bias are obtained for vertical showers with
N
μ
>
10
.
In this article, it is shown that the
C
k
and
LCm
variables, recently introduced as an effective way to discriminate gamma and proton-induced showers in large wide-field gamma-ray observatories, can ...be generalised to be used in arrays of different detectors and variable fill factors. In particular, the
C
k
profile discrimination capabilities are evaluated for scintillator and water Cherenkov detector arrays.
Silicon-substituted hydroxyapatite (SiHA) macroporous scaffolds have been prepared by robocasting. In order to optimize their bone regeneration properties, we have manufactured these scaffolds ...presenting different microstructures: nanocrystalline and crystalline. Moreover, their surfaces have been decorated with vascular endothelial growth factor (VEGF) to evaluate the potential coupling between vascularization and bone regeneration. In vitro cell culture tests evidence that nanocrystalline SiHA hinders pre-osteblast proliferation, whereas the presence of VEGF enhances the biological functions of both endothelial cells and pre-osteoblasts. The bone regeneration capability has been evaluated using an osteoporotic sheep model. In vivo observations strongly correlate with in vitro cell culture tests. Those scaffolds made of nanocrystalline SiHA were colonized by fibrous tissue, promoted inflammatory response and fostered osteoclast recruitment. These observations discard nanocystalline SiHA as a suitable material for bone regeneration purposes. On the contrary, those scaffolds made of crystalline SiHA and decorated with VEGF exhibited bone regeneration properties, with high ossification degree, thicker trabeculae and higher presence of osteoblasts and blood vessels. Considering these results, macroporous scaffolds made of SiHA and decorated with VEGF are suitable bone grafts for regeneration purposes, even in adverse pathological scenarios such as osteoporosis.
For the first time, the in vivo behavior of scaffolds made of silicon substituted hydroxyapatites (SiHA) has been evaluated under osteoporosis conditions. In order to optimize the bone regeneration properties of these bioceramics, 3D macroporous scaffolds have been manufactured by robocasting and implanted in osteoporotic sheep. Our experimental design shed light on the important issue of the biological response of nano-sized bioceramics vs highly crystalline bioceramics, as well as on the importance of coupling vascularization and bone growth processes by decorating SiHA scaffolds with vascular endothelial growth factor.
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