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. STATEMENT OF SIGNIFICANCE 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 an 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

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.

Macroporous scaffolds made of a SiO2-CaO-P2O5 mesoporous bioactive glass (MBG) and ɛpolycaprolactone (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.

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Background: Peri-implant disease (PID) has not been directly linked to pathological organ changes. The present study assessed the dynamics of serum biochemical parameters in a model of experimental peri-implantitis in dogs, followed by open flap debridement. Methods: Seven male beagle dogs comprised the study group. Procedures were performed as follows-extractions of two premolars and one molar on each mandibular quadrant (Day 0); bone healing time (week14); placement of four rough-surface endoosseous implants, two on each mandibular side; implant uncovering (week 28); induction of experimental peri-implantitis by the use of three ligatures (weeks 31, 34, 37) followed by open flap debridement (week 42). Serum biochemical analysis following each procedure was compared to baseline. Biochemical parameters were assigned into four subsets of variablesinflammation, renal function, liver function, and blood glucose. Wilcoxon paired tests were conducted in order to identify statistically significant differences between baseline data and values obtained after each procedure Results: Following experimental peri-implantitis, the dynamics of renal parameters and blood glucose were minimal whereas statistically significant (P < 0.05) increases were noted for inflammatory (total protein and albumin concentrations) and hepatic (ALT, AST) parameters. A statistically significant (P < 0.05) decrease was only noted for total bilirubin. After open flap debridement, inflammatory (total protein and albumin concentrations) and hepatic (AST) parameters returned to baseline. Conclusions: Within their limits, the present results indicate that: (a) PID affects inflammatory and hepatic serum biochemical parameters, and (b) following open flap debridement most of the values returned to baseline.

Training obtained during the first module of our training model significantly decreased performance times for ex vivo urethrovesical anastomosis, simultaneously increasing its quality. In addition, validation of the training model was also demonstrated by the highly scored evaluation resulting from the attendants' assessment.

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BACKGROUND:Congenital obstructive hydrocephalus generates progressive irreversible fetal brain damage by ventricular enlargement and incremental brain tissue compression that leads to maldevelopment and poor clinical outcomes. Intrauterine treatments such as ventriculo-amniotic shunting have been unsuccessfully tried in the eighties.OBJECTIVE:To assess if prenatal endoscopic third ventriculostomy (ETV) is feasible in a large animal model and optimize this technique for ventricular decompression and potential arrest of fetal brain damage in fetal lambs.METHODS:We generated hydrocephalus in 50 fetal lambs by injecting a polymeric agent into the cisterna magna at midgestation (E85). Subsequently, 3 weeks later (E105), fetal ETV was performed using a small rigid fetoscope. The endoscopy entry point was located anterior to the coronal suture, 7 mm from the midline.RESULTS:We obtained clear visualization of the enlarged lateral ventricles by endoscopy in the hydrocephalic fetal lambs. The floor of the third ventricle was bluntly perforated and passed with the scope for a successful ETV. Total success was achieved in 32/50 cases (64%). Causes of failure were blurred vision or third ventricle obliteration by BioGlue in 10/50 (20%) cases, anatomic misdirection of the endoscope in 5 (10%) cases, 2 cases of very narrow foramen of Monro, and 1 case of choroid plexus bleeding. If we exclude the cases artificially blocked by the polymer, we had a successful performance of prenatal-ETV in 80% (32/40) of hydrocephalic fetuses.CONCLUSION:Despite the inherent difficulties arising from ovine brain anatomy, this study shows that innovative fetal ETV is technically feasible in hydrocephalic fetal lambs.