Development and evaluation of copper-containing mesoporous bioactive glasses for bone defects therapy.

Mesoporous bioactive glasses (MBGs) are gaining increasing interest in the design of new biomaterials for bone defects treatment. An important research trend to enhance their biological behavior is the inclusion of moderate amounts of oxides with therapeutical action such as CuO. MBGs with composition (85-x)SiO2-10-CaO-5P2O5-xCuO (x = 0, 2.5 or 5 mol-%) were synthesized, investigating the influence of the CuO content and some synthesis parameters in their properties. Two series were developed; first one used HCl as catalyst and chlorides as CaO and CuO precursors, second one, used HNO3 and nitrates. MBGs of chlorides family exhibited calcium/copper phosphate nanoparticles between 10 and 20 nm in size. Nevertheless, CuO-containing MBGs of nitrates family showed metallic copper nanoparticles larger than 50 nm as well as quicker in vitro bioactive responses. Thus, MBGs of the nitrate series were coated by an apatite-like layer after 24 h soaked in simulated body fluid (SBF) a remarkably short period for a MBG containing 5% of CuO. A model, focused in the location of copper in the glass network, was proposed to relate nanostructure and in vitro behaviour. Moreover, after 24 h soaked in MEM or THB culture media, all the MBGs released therapeutic amounts of Ca2+ and Cu2+ ions. Because the quick bioactive response in SBF, the capacity to host biomolecules in their pores and to release therapeutic concentrations of Ca2+ and Cu2+ ions, MBGs of the nitrate families are proposed as excellent biomaterials for bone regeneration.

ZnO-mesoporous glass scaffolds loaded with osteostatin and mesenchymal cells improve bone healing in a rabbit bone defect.

The use of 3D scaffolds based on mesoporous bioactive glasses (MBG) enhanced with therapeutic ions, biomolecules and cells is emerging as a strategy to improve bone healing. In this paper, the osteogenic capability of ZnO-enriched MBG scaffolds loaded or not with osteostatin (OST) and human mesenchymal stem cells (MSC) was evaluated after implantation in New Zealand rabbits. Cylindrical meso-macroporous scaffolds with composition (mol %) 82.2SiO2-10.3CaO-3.3P2O5-4.2ZnO (4ZN) were obtained by rapid prototyping and then, coated with gelatin for easy handling and potentiating the release of inorganic ions and OST. Bone defects (7.5 mm diameter, 12 mm depth) were drilled in the distal femoral epiphysis and filled with 4ZN, 4ZN + MSC, 4ZN + OST or 4ZN + MSC + OST materials to evaluate and compare their osteogenic features. Rabbits were sacrificed at 3 months extracting the distal third of bone specimens for necropsy, histological, and microtomography (µCT) evaluations. Systems investigated exhibited bone regeneration capability. Thus, trabecular bone volume density (BV/TV) values obtained from µCT showed that the good bone healing capability of 4ZN was significantly improved by the scaffolds coated with OST and MSC. Our findings in vivo suggest the interest of these MBG complete systems to improve bone repair in the clinical practice.

Desing and comparison of bone substitutes. Study of in vivo behavior in a rabbit model. / Diseño y comparativa de biomateriales para el tratamiento de defectos óseos. Estudio de su comportamiento in vivo en modelo animal de conejo.

AIM: Compare bone formation capacity in vivo of two types of biomaterials designed as bone substitutes with respect to iliac crest autograft, one based on carbonate hydroxyapatites and the other one on bioactive mesoporous glass. MATERIALS AND METHODS: Experimental study consisting on 14 adult female New Zeland rabbits where a critical defect was made in the rabbit radius bone. The sample was divided into four groups: defect without material, with iliac crest autograft, with carbonatehydroxyapatite support, and with bioactive mesoporous glass support. Serial X-ray studies were carried out at 2, 4, 6 and 12 weeks and a microCT study at euthanasia at 6 and 12 weeks. RESULTS: In the X-ray study, autograft group showed the highest bone formation scores. Both groups of biomaterials presented bone formation similar and greater than the defect without material, but always less than in the autograft group. The results of the microCT study showed the largest bone volume in the study area in the autograft group. The groups with bone substitutes presented greater bone volume than the group without material but always less than in the autograft group. CONCLUSION: Both supports seem to promote bone formation but are not capable of reproducing the characteristics of autograft. Due to their different macroscopic characteristics, each one could be suitable for a different type of defect.

[Translated article] Design and comparison of bone substitutes. Study of in vivo behaviour in a rabbit model.

AIM: To compare the in vivo bone formation capacity of of biomaterials designed as bone substitutes with respect to iliac crest autograft, one based on carbonate hydroxiapatite and the other one on bioactive mesoporous glass. MATERIALS AND METHODS: Experimental study consisting on 14 adult female New Zeland rabbits where a critical defect was made in the rabbit radius bone. The sample was divided into four groups: defect without material, with iliac crest autograft, with carbonatehydroxyapatite scaffold, and with bioactive mesoporous glass scaffold. Serial X-ray studies were carried out at 2, 4, 6 and 12 weeks and a microCT study at euthanasia at 6 and 12 weeks. RESULTS: In the X-ray study, autograft group showed the highest bone formation scores. Both groups of biomaterials presented bone formation similar and greater than the defect without material, but always less than in the autograft group. The results of the microCT study showed the largest bone volume in the study area in the autograft group. The groups with bone substitutes presented greater bone volume than the group without material but always less than the autograft group. CONCLUSION: Both scaffolds seem to promote bone formation but are not capable of reproducing the characteristics of autograft. Due to their different macroscopic characteristics, each one could be suitable for a different type of defect.

Mullins effect behaviour under compression in micelle-templated silica and micelle-templated silica/agarose systems.

The mechanical properties of bioceramic conformed pieces based on micelle-templated silica (MTS) such as SBA15, MCM41 and MCM48 as well as MTS/agarose systems have been evaluated under static and cyclic compressive tests. The MTS pieces exhibited a brittle behaviour. Agarose, a biocompatible and biodegradable hydrogel, has been used to shape ceramic-agarose pieces following a low temperature shaping method. Agarose conferred toughness, ductility and a rubbery consistency up to a 60% strain in ceramic MTS/agarose systems leading to a maximum strength of 10-50 MPa, without losing their initial cylindrical structure. This combination of ceramic and organic matrix contributes to avoiding the inherent brittleness of the bioceramic and enhances the compression resistance of hydrogel. The presence of mechanical hysteresis, permanent deformation after the first cycle and recovery of the master monotonous curve of MTS/agarose systems indicate a Mullins-like effect similar to that found in carbon-filled rubber systems. We report this type of mechanical behaviour, the Mullins effect, for the first time in MTS bioceramics and MTS bioceramic/agarose systems.

Knowledge, attitudes, and behavior regarding antibiotics, antibiotic use, and antibiotic resistance in students and health care professionals of the district of Barranquilla (Colombia): A cross-sectional survey.

Objective: To evaluate the knowledge, attitudes and behavior regarding antibiotics, use of antibiotics, and antibiotic resistance in students and health care professionals of the district of Barranquilla, Colombia. Study design: Descriptive, cross-sectional. Methods: A sample of 399 respondents was selected, that included health professionals and medical students from 12 health institutions in the district of Barranquilla (Colombia), using an established stratified sampling method. Each of the respondent professionals completed a survey that included 43 items in the Likert scale. A descriptive analysis of the study variables was performed using the software SPSS version 25. Results: Most of the respondents were women (64.4%), aged between 26 and 35 years (47.6%); 28.8% were nurses and 26.1% general practitioners, with ≤10 years of professional experience (63.4%). Overall, the survey revealed that the participants had considerable knowledge about antibiotic use (89.5%-98% correct answers) and the spread of antibiotic resistance (67.4%-89% correct answers). Approximately 74% of the respondents agreed or fully agreed with the questions related to the management of infections and the provision of advice. Conclusions: The present study revealed that most of the health care professionals surveyed had a good knowledge about antibiotic use, although strategies must be developed to strengthen knowledge regarding the spread of antibiotic resistance. Likewise, it is important to identify opportunities for improvement related with access to the guidelines and/or materials necessary to treat infections and to provide advice on antibiotic use and antibiotic resistance.

Multifunctional antibiotic- and zinc-containing mesoporous bioactive glass scaffolds to fight bone infection.

Bone regeneration is a clinical challenge which requires multiple approaches. Sometimes, it also includes the development of osteogenic and antibacterial biomaterials to treat the emergence of possible infection processes arising from surgery. This study evaluates the antibacterial properties of gelatin-coated meso-macroporous scaffolds based on the bioactive glass 80%SiO2-15%CaO-5%P2O5 (mol-%) before (BL-GE) and after being doped with 4% of ZnO (4ZN-GE) and loaded with both saturated and the minimal inhibitory concentrations of one of the antibiotics: levofloxacin (LEVO), vancomycin (VANCO), rifampicin (RIFAM) or gentamicin (GENTA). After physical-chemical characterization of materials, release studies of inorganic ions and antibiotics from the scaffolds were carried out. Moreover, molecular modelling allowed determining the electrostatic potential density maps and the hydrogen bonds of antibiotics and the glass matrix. Antibacterial in vitro studies (in planktonic, inhibition halos and biofilm destruction) with S. aureus and E. coli as bacteria models showed a synergistic effect of zinc ions and antibiotics. The effect was especially noticeable in planktonic cultures of S. aureus with 4ZN-GE scaffolds loaded with VANCO, LEVO or RIFAM and in E. coli cultures with LEVO or GENTA. Moreover, S. aureus biofilms were completely destroyed by 4ZN-GE scaffolds loaded with VANCO, LEVO or RIFAM and the E. coli biofilm total destruction was accomplished with 4ZN-GE scaffolds loaded with GENTA or LEVO. This approach could be an important step in the fight against microbial resistance and provide needed options for bone infection treatment. STATEMENT OF SIGNIFICANCE: Antibacterial capabilities of scaffolds based on mesoporous bioactive glasses before and after adding a 4% ZnO and loading with saturated and minimal inhibitory concentrations of levofloxacin, vancomycin, gentamicin or rifampicin were evaluated. Staphylococcus aureus and Escherichia coli were the infection model strains for the performed assays of inhibition zone, planktonic growth and biofilm. Good inhibition results and a synergistic effect of zinc ions released from scaffolds and antibiotics were observed. Thus, the amount of antibiotic required to inhibit the bacterial planktonic growth was substantially reduced with the ZnO inclusion in the scaffold. This study shows that the ZnO-MBG osteogenic scaffolds are multifunctional tools in bone tissue engineering because they are able to fight bacterial infections with lower antibiotic dosage.

Silicon substituted hydroxyapatite/VEGF scaffolds stimulate bone regeneration 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. STATEMENT OF SIGNIFICANCE: 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.

Antibiotic resistance profile in eye infections in a reference centre in Floridablanca, Colombia. / Perfil de resistencia antibiótica en infecciones oculares en un centro de referencia en Floridablanca, Colombia.

BACKGROUND AND OBJECTIVE: In view of the increasing bacterial resistance to antibiotics, it is necessary to determine it locally in order to serve as a guide in clinical management. The purpose of this study was to characterise the pattern of antibiotic sensitivity in cases of eye infections in a third level ophthalmological institution in Floridablanca (Colombia). MATERIALS AND METHODS: An observational cross-sectional study in which an analysis was made of the culture and antibiogram reports of specimens taken from cases of conjunctivitis, infectious keratitis, and endophthalmitis between January 2013 and June 2016. RESULTS: A total of 833 specimens were positive for bacteria. Considering both gram-positive and gram-negative microorganisms gentamicin, tobramycin, and ciprofloxacin showed high resistance rates (64.4%, 40.3%, and 29.1%, respectively). Moxifloxacin, vancomycin, imipenem, and gatifloxacin showed low percentages of resistance: 2.6%, 2.1%, 0.6%, and 0.4%, respectively. When comparing the results with previous studies in our institution, there was a decrease in sensitivity to the fourth-generation quinolones and imipenem, especially within the gram-negative ones. CONCLUSION: Fourth generation quinolones, imipenem and vancomycin continue to have a low in vitro resistance to bacteria that cause eye infections. However, there was a tendency to an increase in the resistance of gram-negative bacteria. Measures should be taken to try to control this phenomenon, and consider possible antimicrobial therapy alternatives to infections caused by these microorganisms.

Cerium (III) and (IV) containing mesoporous glasses/alginate beads for bone regeneration: bioactivity, biocompatibility and reactive oxygen species activity.

A very small number of biomaterials investigated for bone regeneration was reported as able to prevent the oxidative stress. In this study beads based on alginate hydrogel and mesoporous glasses (MG) containing different amounts of cerium oxides (Ce3+/Ce4+) exhibiting antioxidant properties were investigated as a good approach to mimic the action of antioxidant enzymes in our organism. The effect of cerium contents on the bioactivity and biocompatibility of beads were investigated. Moreover, the potential capability of Ce-containing MG to prevent the oxidative stress caused by the activity of reactive oxygen species (ROS) was here investigated for the first time. The increment of cerium oxide from 1.2, to 3.6 and 5.3 mol-% decreases the surface area and porosity of MG and increases the catalase mimetic activity after 168 h. Swelling tests in different cell culture media (D- and α-MEM) demonstrated the rehydration capability of beads. The presence of beads with the highest Ce-contents (3.6 and 5.3 %) improved the proliferation of pre-osteoblastic cells MC3T3-Cl cells. However, the cell differentiation decreased when increased the cerium content. Lactate dehydrogenase assays showed beads are cytocompatible materials. Moreover, oxidative stress tests with H2O2 showed a better response related to cell viability and the elimination of oxidant species when increased cerium content. Beads of glasses with 1.2 and 3.6 % of CeO2 are excellent candidates as bioactive scaffolds for bone regeneration capable of counteract the oxidative stress.

Cerium (III) and (IV) containing mesoporous glasses/alginate beads for bone regeneration: Bioactivity, biocompatibility and reactive oxygen species activity.

A very small number of biomaterials investigated for bone regeneration were reported as able to prevent the oxidative stress. In this study beads based on alginate hydrogel and mesoporous glasses (MG) containing different amounts of cerium oxides (Ce3+/Ce4+) exhibiting antioxidant properties were investigated as a good approach to mimic the action of antioxidant enzymes in our organism. The effect of cerium contents on the bioactivity and biocompatibility of beads were investigated. Moreover, the potential capability of Ce-containing MG to prevent the oxidative stress caused by the activity of reactive oxygen species (ROS) was here investigated for the first time. The increment of cerium oxide from 1.2, to 3.6 and 5.3 mol% decreases the surface area and porosity of MG and increases the catalase mimetic activity after 168 h. Swelling tests in different cell culture media (D- and α-MEM) demonstrated the rehydration capability of beads. The presence of beads with the highest Ce-contents (3.6 and 5.3%) improved the proliferation of pre-osteoblastic cells MC3T3-C1 cells. However, the cell differentiation decreased when increased the cerium content. Lactate dehydrogenase assays showed beads are cytocompatible materials. Moreover, oxidative stress tests with H2O2 showed a better response related to cell viability and the elimination of oxidant species when increased cerium content. Beads of glasses with 1.2 and 3.6% of CeO2 are excellent candidates as bioactive scaffolds for bone regeneration capable of counteract the oxidative stress.

Osteostatin potentiates the bioactivity of mesoporous glass scaffolds containing Zn2+ ions in human mesenchymal stem cells.

There is an urgent need of biosynthetic bone grafts with enhanced osteogenic capacity. In this study, we describe the design of hierarchical meso-macroporous 3D-scaffolds based on mesoporous bioactive glasses (MBGs), enriched with the peptide osteostatin and Zn2+ ions, and their osteogenic effect on human mesenchymal stem cells (hMSCs) as a preclinical strategy in bone regeneration. The MBG compositions investigated were 80%SiO2-15%CaO-5%P2O5 (in mol-%) Blank (BL), and two analogous glasses containing 4% ZnO (4ZN) and 5% ZnO (5ZN). By using additive fabrication techniques, scaffolds exhibiting hierarchical porosity: mesopores (around 4 nm), macropores (1-600 µm) and big channels (∼1000 µm), were prepared. These MBG scaffolds with or without osteostatin were evaluated in hMCSs cultures. Zinc promoted hMSCs colonization (both the surface and inside) of MBG scaffolds. Moreover, Zn2+ ions and osteostatin together, but not independently, in the scaffolds were found to induce the osteoblast differentiation genes runt related transcription factor-2 (RUNX2) and alkaline phosphatase (ALP) in hMSCs after 7 d of culture in the absence of an osteogenic differentiation-promoting medium. These results add credence to the combined use of zinc and osteostatin as an effective strategy for bone regeneration applications. STATEMENT OF SIGNIFICANCE: Mesoporous bioactive glasses (MBGs) are bioceramics whose unique properties make them excellent materials for bone tissue engineering. Physico-chemical characterization of MBGs as scaffolds made by rapid prototyping, doped with zinc (potential osteogenic, angiogenic and bactericidal ion) and loaded with osteostatin (osteogenic peptide) are described. These Zn-MBGs scaffolds showed 3D hierarchical meso-macroporous structure that enables to host and release osteostatin. When decorated with human mesenchymal stem cells (hMSCs), MBGs scaffoldsenriched with both zinc and osteostatin exhibited a synergistic effect to enhance hMSCs growth, and also hMSCs osteogenic differentiationwithout addition of other osteoblastic differentiation factors to the culture medium. This novel strategy has a great potential for use in bone tissue engineering.

Hierarchical pore structure of calcium phosphate scaffolds by a combination of gel-casting and multiple tape-casting methods.

The objective of this work was to design hierarchical pore structure scaffolds with potential applications in bone tissue regeneration. For that purpose, a bioceramic material such as biphasic calcium phosphate, which consists of a mixture of hydroxyapatite and beta-tricalcium phosphate, was selected. Multilayer pieces (MLP) with hierarchical pore structure were developed employing a new technique that combines gel casting and adding porogens, using multiple tape-casting methods. Pieces with functionally graded porosity were fabricated using porogens with different sizes. The porogens used were Porlat K85 and Porlat K86 with diameters <150 microm and 150-300 microm, respectively. Two types of sintered tapes, with different porosity, no cracking and enough interconnection size were selected. MLP with hierarchical pore structure were designed by the multiple tape-casting method. Interconnected pores whose sizes increase from interior tapes (1.6-3.6 microm) towards exterior tapes (20-51.5 microm) and interpenetration between tapes were achieved. Delamination or cracking were not observed after heat treatment. The flexural strength of pieces was investigated by the three-point bending test. This new combination of methods offers the possibility of manufacturing scaffolds with interconnected pore sizes ranging from 1.6 to 51.5 microm.

In vitro behaviour of adult mesenchymal stem cells seeded on a bioactive glass ceramic in the SiO(2)-CaO-P(2)O(5) system.

This work describes the evaluation of a glass ceramic (55S41C4P-1300) as a potential substrate for bone tissue engineering. For that purpose, the capacity of mesenchymal stem cells (MSCs), isolated from rabbit bone marrow, to adhere, proliferate and differentiate into osteoblast (OBs) with or without 55S41C4P-1300 was investigated. Two types of culture medium, i.e. growth medium (GM) and osteogenic medium (OM), were evaluated. The bioactive 55S41C4P-1300, containing pseudowollastonite, wollastonite, tricalcium phosphate and crystoballite as crystalline phases, was obtained by heat treatment of a sol-gel glass (55SiO(2), 41CaO, 4P(2)O(5) (mol.%)) at 1300 degrees C. The results showed that the MSCs adhered, spread, proliferated and produced mineralized extracellular matrix on 55S41C4P-1300 regardless of the culture medium used. As the same time, they showed an osteoblastic phenotype, and this phenomenon was accompanied by the gradual diminution of the marker CD90 expression. The 55S41C4P-1300 was able to induce the differentiation of MSCs into OBs in the same way as OM without glass ceramic. This effect increased with the combination of 55S41C4P-1300 with OM. The glass ceramic evaluated in this work is bioactive, cytocompatible and capable of promoting the differentiation of MSCs into OBs. For that reason, it could be regarded as a suitable matrix in tissue engineering for bone tissue regeneration.

Use of nonabsorbable polymer ligaclip in hand-assisted laparoscopic nephrectomy for living donor.

BACKGROUND: Laparoscopic living donor nephrectomy for kidney transplantation is a technique that began in South America only recently. This procedure offers several advantages compared with open nephrectomy due to the minor pain, better cosmetic results, and shorter length of hospital stay. Herein we have described our experience with the use of nonabsorbable polymer ligaclip (NPL) to control the renal artery, vein, and ureter in hand-assisted laparoscopic donor nephrectomy (HALN). METHODS: We performed a review of 85 HALNs for renal transplantation at our institution between January 2004 and August 2007. We evaluated the preoperative characteristics of the donor, surgical parameters, and complications. RESULTS: Fifty six percent of donors were men. Mean donor age was 34.4 years (range = 18 to 60). Left-sided nephrectomy was performed in 85%. Mean surgical time was 132 minute (range = 90 to 240) and among the last 35 nephrectomies, 120 minute (range = 90 to 180). Mean warm ischemia time was 240 seconds (range = 120 to 420). Conversion rate was 1.1%. Mortality was one case (1.1%) secondary to an episode of massive pulmonary thromboembolism. Mean length of hospital stay was 2.5 days (range 2 to 5) and mean blood loss, 125 mL. No complication related to the NPL was observed. CONCLUSIONS: Laparoscopy living donor nephrectomy was a safe procedure for kidney transplantation. The training and experience of the surgeon was reflected in shorter times of surgery. The NPL was safe and cost-effective, not increasing morbidity of the procedure.

Experience with Alemtuzumab (Campath-1H) as induction agent in renal transplantation followed by steroid-free immunosuppression.

BACKGROUND: The purpose of this study was to describe the initial experience with alemtuzumab as induction followed by steroid-free immunosuppression in kidney transplantation. METHODS: One hundred patients who received renal transplants from living and deceased donors were followed for a median period of 12 months (range = 1 to 12). A 30-mg intravenous dose of Alemtuzumab was administered on the transplant day, preceded by a 500-mg methylprednisolone dose. Maintenance immunosuppression consisted in the use of a calcineurin inhibitor in association with mycophenolic acid. Maintenance C2 levels of cyclosporine were between 400 and 600 ng/dL; or of tacrolimus, between 4 and 7 ng/dL. Prophylaxis included valgancyclovir, trimethoprim-sulfamethoxasole, and nystatin. All patients were evaluated for acute rejection episodes, adverse events, or death. RESULTS: The cumulative incidences of acute rejection at 1, 3, 6, and 12 months were 0%, 4% (n = 4), 5% (n = 5), and 8% (n = 8), respectively. Most episodes were Banff 1 a or b (88%). The infectious complication rate was 23%. There was no case of cytomegalovirus infection or posttransplant lymphoproliferative disease. Three patients died: one due to tuberculosis; one, sepsis; and one, an acute coronary event. No patient was lost to follow-up. CONCLUSIONS: This study suggested the safety and efficacy of Campath-1H as an induction agent in renal transplant recipients.

Conversion therapy to everolimus in renal transplant recipients: results after one year.

BACKGROUND: Two new diagnoses have been causing graft loss during long-term follow-up, namely, chronic nephropathy and anticalcineurinic toxicity. The advent of the mammalian target of rapamycin (m-TOR) obviates anticalcineurine toxicity and reduces posttransplant malignancy incidence with good inmunosuppressive potential. We examinated the renal and metabolic behavior in renal transplant recipients who required conversion from an anticalcineurinic (cyclosporine or tacrolimus) to an m-TOR inhibitor (everolimus) as part of their immunosuppressive maintenance therapy. MATERIALS AND METHODS: Twenty-one first renal transplant recipients had everolimus added to their inmunosuppressive therapy combined with an antimetabolite (mycophenolate mofetil or sodium mycophenolate). The mean age of the patients was 35 +/- 17 years (range, 6 to 65). The prevalence of male recipients was 57%; the overall mean weight, 64 kg (range, 48 to 95). All patients were hispanic with 15 transplants from cadaveric donors (71%). The mean follow-up posttransplant was 18 months (range, 3 to 40) and the mean follow-up on everolimus, 10 months (range, 2 to 22). RESULTS: There was no mortality or graft loss, but there were 3 (17%) biopsy-confirmed acute rejection episodes. There were no significant changes in metabolic function pre- or postconversion. Regarding renal function, the mean creatinine serum showed a trend to decline: preconversion 1.7 mg/dL; postconversion 1.5 mg/dL. In 10 patients, it was possible to discontinue at least one antihypertensive medication (48%). CONCLUSIONS: Everolimus was an effective medication to manage renal transplant patients. It produced metabolic stability and low myelotoxicity, despite combination with an antimetabolite (mycophenolic acid). Also, reduction of antihypertensive medications was an additional benefits for many patients.

Diseño y comparativa de biomateriales para el tratamiento de defectos óseos. Estudio de su comportamiento in vivo en modelo animal de conejo / Desing and comparison of bone substitutes. Study of in vivo behavior in a rabbit model

Objetivo: Comparar in vivo la capacidad de formación ósea de dos tipos de biomateriales diseñados como sustitutivos óseos respecto a autoinjerto de cresta iliaca, uno basado en carbonatohidroxiapatita y otro en vidrio mesoporoso bioactivo. Material y método: Estudio experimental compuesto por 14 conejos de Nueva Zelanda hembras adultas donde se realizó un defecto crítico en hueso radio. La muestra fue dividida en cuatro grupos: defecto sin material, con autoinjerto de cresta iliaca, con soporte de carbonatohidroxiapatita y con soporte de vidrio mesoporoso bioactivo. Se realizaron estudios seriados de radiología simple a las 2, 4, 6 y 12 semanas y estudio de micro-TC a eutanasia a las 6 y 12 semanas. Resultados: En el estudio de radiología simple, el grupo de autoinjerto mostró las mayores puntuaciones de formación ósea (7,5 puntos). Ambos grupos de biomateriales presentaron formación ósea similar (5,3 y 6 puntos, respectivamente) y mayor al defecto sin material (4 puntos), pero siempre menor que el grupo de autoinjerto. Los resultados del estudio de micro-TC mostraron el mayor volumen de hueso en el área de estudio en el grupo de autoinjerto. Los grupos con sustitutivos óseos presentaron mayor volumen de hueso que el grupo sin material, pero siempre menor que en el grupo de autoinjerto. Conclusiones: Ambos soportes parecen favorecer la formación ósea pero no son capaces de reproducir las características del autoinjerto. Por sus diferentes características macroscópicas cada uno podría ser adecuado para un tipo diferente de defecto.(AU)

Aim: Compare bone formation capacity in vivo of two types of biomaterials designed as bone substitutes with respect to iliac crest autograft, one based on carbonate hydroxyapatites and the other one on bioactive mesoporous glass. Materials and methods: Experimental study consisting on 14 adult female New Zeland rabbits where a critical defect was made in the rabbit radius bone. The sample was divided into four groups: defect without material, with iliac crest autograft, with carbonatehydroxyapatite support, and with bioactive mesoporous glass support. Serial X-ray studies were carried out at 2, 4, 6 and 12 weeks and a microCT study at euthanasia at 6 and 12 weeks. Results: In the X-ray study, autograft group showed the highest bone formation scores. Both groups of biomaterials presented bone formation similar and greater than the defect without material, but always less than in the autograft group. The results of the microCT study showed the largest bone volume in the study area in the autograft group. The groups with bone substitutes presented greater bone volume than the group without material but always less than in the autograft group. Conclusion: Both supports seem to promote bone formation but are not capable of reproducing the characteristics of autograft. Due to their different macroscopic characteristics, each one could be suitable for a different type of defect.(AU)

[Translated article] Design and comparison of bone substitutes. Study of in vivo behaviour in a rabbit model / Diseño y comparativa de biomateriales para el tratamiento de defectos óseos. Estudio de su comportamiento in vivo en modelo animal de conejo

Objetivo: Comparar in vivo la capacidad de formación ósea de dos tipos de biomateriales diseñados como sustitutivos óseos respecto a autoinjerto de cresta iliaca, uno basado en carbonatohidroxiapatita y otro en vidrio mesoporoso bioactivo. Material y método: Estudio experimental compuesto por 14 conejos de Nueva Zelanda hembras adultas donde se realizó un defecto crítico en hueso radio. La muestra fue dividida en cuatro grupos: defecto sin material, con autoinjerto de cresta iliaca, con soporte de carbonatohidroxiapatita y con soporte de vidrio mesoporoso bioactivo. Se realizaron estudios seriados de radiología simple a las 2, 4, 6 y 12 semanas y estudio de micro-TC a eutanasia a las 6 y 12 semanas. Resultados: En el estudio de radiología simple, el grupo de autoinjerto mostró las mayores puntuaciones de formación ósea (7,5 puntos). Ambos grupos de biomateriales presentaron formación ósea similar (5,3 y 6 puntos, respectivamente) y mayor al defecto sin material (4 puntos), pero siempre menor que el grupo de autoinjerto. Los resultados del estudio de micro-TC mostraron el mayor volumen de hueso en el área de estudio en el grupo de autoinjerto. Los grupos con sustitutivos óseos presentaron mayor volumen de hueso que el grupo sin material, pero siempre menor que en el grupo de autoinjerto. Conclusiones: Ambos soportes parecen favorecer la formación ósea pero no son capaces de reproducir las características del autoinjerto. Por sus diferentes características macroscópicas cada uno podría ser adecuado para un tipo diferente de defecto.(AU)

Aim: Compare bone formation capacity in vivo of two types of biomaterials designed as bone substitutes with respect to iliac crest autograft, one based on carbonate hydroxyapatites and the other one on bioactive mesoporous glass. Materials and methods: Experimental study consisting on 14 adult female New Zeland rabbits where a critical defect was made in the rabbit radius bone. The sample was divided into four groups: defect without material, with iliac crest autograft, with carbonatehydroxyapatite support, and with bioactive mesoporous glass support. Serial X-ray studies were carried out at 2, 4, 6 and 12 weeks and a microCT study at euthanasia at 6 and 12 weeks. Results: In the X-ray study, autograft group showed the highest bone formation scores. Both groups of biomaterials presented bone formation similar and greater than the defect without material, but always less than in the autograft group. The results of the microCT study showed the largest bone volume in the study area in the autograft group. The groups with bone substitutes presented greater bone volume than the group without material but always less than in the autograft group. Conclusion: Both supports seem to promote bone formation but are not capable of reproducing the characteristics of autograft. Due to their different macroscopic characteristics, each one could be suitable for a different type of defect.(AU)

Bioactive glass as precursor of designed-architecture scaffolds for tissue engineering.

In this work, the conditions to obtain concentrated and fluid suspensions from a bioactive glass (55-SiO(2); 41-CaO; 4-P(2)O(5); mol %) were investigated. The influence of the heat treatment of the glass on the specific surface area, solubility, bioactivity, and finally on their dispersion characteristics was studied. Zeta potential and viscosity measurements were carried out, and based on the obtained results, the best dispersant was selected. The optimum concentration of dispersant, maximum content of solid and time of mixing were also investigated. Slurries containing 50 vol % could be obtained calcining the glass at 1100 degrees C and using Darvan 811 (sodium polyacrylate) as dispersant. Scaffolds with designed architecture were prepared from these suspensions combining the gelcasting method and the stereolithography technique. A polymeric negative (replica of the desired structure) was previously obtained by stereolithography. The slurry was cast into the molds and then polymerized (gelcasting method). The negative was eliminated by heat treatment. After sintering at 1300 degrees C, scaffolds with interconnected porosity and three-dimensional channels of 400-470 microm and macropores of 1.4 microm were obtained.