Emergency surgery for brainstem cavernoma haemorrhage with severe neurological presentation. Is it indicated and worthwhile?

Background: Brainstem Cavernoma (BSCM) haemorrhage is a complex condition, especially when patients present rapid neurological deterioration. Traditionally, these patients were initially treated by non-interventional means. Surgery was generally reserved for cases who presented a 'benign' evolution in a subacute/delayed fashion. Timing of surgery remains controversial. Since rebleeding is frequent and carries a high mortality, many of these patients do not tolerate this approach. Urgent/emergent surgery may be indicated and lifesaving.Methods: A single center experience is reported in which an aggressive approach was used with urgent/emergency surgery carried out on patients with BSCM haemorrhage and rapid neurological deterioration, ventilatory impairment and/or coma. A review of 5 consecutive cases where urgent/emergent surgery was performed is presented. The pre-operative status, pre- and post-operative examinations, surgical approach and neurological residual deficits/outcomes are reported.Results: Four females and one male with ages ranging from 36 to 66 years with rapid neurological deterioration, ventilatory impairment and/or coma were operated between 2011 and 2018. Favourable outcomes were observed with a modified Rankin Scale varying from 1 to 4. Cranial nerve deficits as well as motor and sensitive deficits were observed but all the patients recovered cognitive integrity.Conclusions: Our small series reveals an acceptable outcome with ultra-early surgery. This approach appears to be a valid option when there is rapid neurological deterioration, respiratory impairment and/or early onset coma. However, further studies are required to elucidate the optimal strategy.

Multifunctional bioactive glass and glass-ceramic biomaterials with antibacterial properties for repair and regeneration of bone tissue.

Bioactive glasses (BGs) and related glass-ceramic biomaterials have been used in bone tissue repair for over 30years. Previous work in this field was comprehensively reviewed including by their inventor Larry Hench, and the key features and properties of BGs are well understood. More recently, attention has focused on their modification to further enhance the osteogenic behaviour, or further compositional changes that may introduce additional properties, such as antimicrobial activity. Evidence is emerging that BGs and related glass-ceramics may be modified in such a way as to simultaneously introduce more than one desirable property. The aim of this review is therefore to consider the evidence that these more recent inorganic modifications to glass and glass-ceramic biomaterials are effective, and whether or not these new compositions represent sufficiently versatile systems to underpin the development of a new generation of truly multifunctional biomaterials to address pressing clinical needs in orthopaedic and dental surgery. Indeed, a number of classical glass compositions exhibited antimicrobial activity, however the structural design and the addition of specific ions, i.e. Ag+, Cu+, and Sr2+, are able to impart a multifunctional character to these systems, through the combination of, for example, bioactivity with bactericidal activity. STATEMENT OF SIGNIFICANCE: In this review we demonstrate the multifunctional potential of bioactive glasses and related glass-ceramics as biomaterials for orthopaedic and craniofacial/dental applications. Therefore, it considers the evidence that the more recent inorganic modifications to glass and glass-ceramic biomaterials are able to impart antimicrobial properties alongside the more classical bone bonding and osteoconduction. These properties are attracting a special attention nowadays that bacterial infections are an increasing challenge in orthopaedics. We also focus the manuscript on the versatility of these systems as a basis to underpin the development of a new generation of truly multifunctional biomaterials to address pressing clinical needs in orthopaedic, craniofacial and dental surgery.

* Substituted Borosilicate Glasses with Improved Osteogenic Capacity for Bone Tissue Engineering.

Borosilicate bioactive glasses (BBGs) have shown the capacity to promote higher formation of new bone when compared with silicate bioactive glasses. Herein, we assessed the capacity of BBGs to induce osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) as a function of their substituted divalent cations (Mg2+, Ca2+, Sr2+). To this purpose, we synthesized BBG particles by melt quenching. The cell viability, proliferation, and morphology (i.e., PrestoBlue®, PicoGreen®, and DAPI and Phalloidin stainings, respectively), as well as protein expression (i.e., alkaline phosphatase, ALP; osteopontin, OP; and osteocalcin, OC), of BM-MSCs in contact with BBGs were evaluated for 21 days. We observed an enhanced expression of bone-specific proteins (ALP, OP, and OC) and high mineralization of BM-MSCs under BBG-Mg and BBG-Sr-conditioned osteogenic media for concentrations of 20 and 50 mg/mL with low cytotoxic effects. Moreover, BBG-Sr, at a concentration of 50 mg/mL, was able to increase the mineralization and expression of the same bone-specific proteins even under basal medium conditions. These results indicated that the proposed BBGs improved osteogenic differentiation of BM-MSCs, therefore showing their potential as relevant biomaterials for bone tissue regeneration, not only by bonding to bone tissue but also by stimulating new bone formation.

Wetspun poly-L-(lactic acid)-borosilicate bioactive glass scaffolds for guided bone regeneration.

We developed a porous poly-L-lactic acid (PLLA) scaffold compounded with borosilicate bioactive glasses (BBGs) endowing it with bioactive properties. Porous PLLA-BBG fibre mesh scaffolds were successfully prepared by the combination of wet spinning and fibre bonding techniques. Micro-computed tomography (µCT) confirmed that the PLLA-BBG scaffolds containing ≈25% of BBGs (w/w) exhibited randomly interconnected porous (58 to 62% of interconnectivity and 53 to 67% of porosity) with mean pore diameters higher that 100µm. Bioactivity and degradation studies were performed by immersing the scaffolds in simulated body fluid (SBF) and ultrapure water, respectively. The PLLA-BBG scaffolds presented a faster degradation rate with a constant release of inorganic species, which are capable to produce calcium phosphate structures at the surface of the material after 7days of immersion in SBF (Ca/P ratio of ~1.7). Cellular in vitro studies with human osteosarcoma cell line (Saos-2) and human adipose-derived stem cells (hASCs) showed that PLLA-BBGs are not cytotoxic to cells, while demonstrating their capacity to promote cell adhesion and proliferation. Overall, we showed that the proposed scaffolds present a tailored kinetics on the release of inorganic species and controlled biological response under conditions that mimic the bone physiological environment.

Reinforcement of poly-l-lactic acid electrospun membranes with strontium borosilicate bioactive glasses for bone tissue engineering.

UNLABELLED: Herein, for the first time, we combined poly-l-lactic acid (PLLA) with a strontium borosilicate bioactive glass (BBG-Sr) using electrospinning to fabricate a composite bioactive PLLA membrane loaded with 10% (w/w) of BBG-Sr glass particles (PLLA-BBG-Sr). The composites were characterised by scanning electron microscopy (SEM) and microcomputer tomography (µ-CT), and the results showed that we successfully fabricated smooth and uniform fibres (1-3µm in width) with a homogeneous distribution of BBG-Sr microparticles (<45µm). Degradation studies (in phosphate buffered saline) demonstrated that the incorporation of BBG-Sr glass particles into the PLLA membranes increased their degradability and water uptake with a continuous release of cations. The addition of BBG-Sr glass particles enhanced the membrane's mechanical properties (69% higher Young modulus and 36% higher tensile strength). Furthermore, cellular in vitro evaluation using bone marrow-derived mesenchymal stem cells (BM-MSCs) demonstrated that PLLA-BBG-Sr membranes promoted the osteogenic differentiation of the cells as demonstrated by increased alkaline phosphatase activity and up-regulated osteogenic gene expression (Alpl, Sp7 and Bglap) in relation to PLLA alone. These results strongly suggest that the composite PLLA membranes reinforced with the BBG-Sr glass particles have potential as an effective biomaterial capable of promoting bone regeneration. STATEMENT OF SIGNIFICANCE: PLLA membranes were reinforced with 10% (w/w) of strontium-bioactive borosilicate glass microparticles, and their capacity to induce the osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) was evaluated. These membranes presented an increased: degradability, water uptake, Young modulus and tensile strength. We also demonstrated that these membranes are non-cytotoxic and promote the attachment of BM-MSCs. The addition of the glass microparticles into the PLLA membranes promoted the increase of ALP activity (under osteogenic conditions), as well as the BM-MSCs osteogenic differentiation as shown by the upregulation of Alpl, Sp7 and Bglap gene expression. Overall, we demonstrated that the reinforcement of PLLA with glass microparticles results in a biomaterial with the appropriate properties for the regeneration of bone tissue.

Intrinsic Antibacterial Borosilicate Glasses for Bone Tissue Engineering Applications.

Three novel borosilicate bioactive glasses (BBGs) were prepared and used to investigate their bioactive and antibacterial properties. The BBGs were prepared by melt-quenching using different glass modifiers, i.e. Mg2+, Ca2+, and Sr2+, and their amorphous nature was confirmed by X-ray diffraction. Scanning electron microscopy with energy dispersive X-ray spectroscopy allowed the visualization of apatite-like structures upon 7 days of immersion in simulated body fluid. BBG-Ca generated surface structures with a Ca/P ratio ≈1.67, while the surface of the BBG-Sr was populated with structures with a Sr/P ratio ≈1.7. Moreover, bacterial tests showed that the BBG-Mg and BBG-Sr glasses (at concentrations of 9, 18, 36, and 72 mg/mL) present antibacterial characteristics. In particular, BBG-Sr, at concentrations of 9 mg/mL, exhibited bacteriostatic activity against Pseudomonas aeruginosa, and at concentrations ≥18 mg/mL it was able to eradicate this bacterium. These results evidence an antibacterial activity dependent on the BBGs composition, concentration, and bacterial species. Cellular studies showed that the developed BBGs do not present a statistically significant cytotoxic effect against Saos-2 cells after 3 days of culture, showing better performance (in the cases of BBG-Ca and BBG-Sr) than commercial 45S5 Bioglass up to 7 days of culture. Overall, this study demonstrates that BBGs can be effectively designed to combine bioactivity and intrinsic antibacterial activity targeting bone tissue engineering applications.

Determination of microcystin-LR in waters in the subnanomolar range by sol-gel imprinted polymers on solid contact electrodes.

The present work reports new sensors for the direct determination of Microcystin-LR (MC-LR) in environmental waters. Both selective membrane and solid contact were optimized to ensure suitable analytical features in potentiometric transduction. The sensing layer consisted of Imprinted Sol-Gel (ISG) materials capable of establishing surface interactions with MC-LR. Non-Imprinted Sol-Gel (NISG) membranes were used as negative control. The effects of an ionic lipophilic additive, time of sol-gel polymerization, time of extraction of MC-LR from the sensitive layer, and pH were also studied. The solid contact was made of carbon, aluminium, titanium, copper or nickel/chromium alloys (80 : 20 or 90 : 10). The best ISG sensor had a carbon solid contact and displayed average slopes of 211.3 mV per decade, with detection limits of 7.3 × 10(-10) M, corresponding to 0.75 µg L(-1). It showed linear responses in the range of 7.7 × 10(-10) to 1.9 × 10(-9) M of MC-LR (corresponding to 0.77-2.00 µg L(-1)), thus including the limiting value for MC-LR in waters (1.0 µg L(-1)). The potentiometric-selectivity coefficients were assessed by the matched potential method for ionic species regularly found in waters up to their limiting levels. Chloride (Cl(-)) showed limited interference while aluminium (Al(3+)), ammonium (NH(4)(+)), magnesium (Mg(2+)), manganese (Mn(2+)), sodium (Na(+)), and sulfate (SO(4)(2-)) were unable to cause the required potential change. Spiked solutions were tested with the proposed sensor. The relative errors and standard deviation obtained confirmed the accuracy and precision of the method. It also offered the advantages of low cost, portability, easy operation and suitability for adaptation to flow methods.