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Osseointegration capacity and good mechanical behavior are key to the success of the dental implant. In many investigations, comparisons of properties are made using different dental implant designs and therefore the results can be influenced by the macrodesign of the dental implant. In this work, studies were carried out with the same dental implant model using different roughness and different materials—commercially pure titanium (grade 4) and zirconia. For this purpose, 80 smooth passivated titanium (Ti), 80 smooth zirconia (ZrO2), and 80 rough passivated titanium (Ti-R) dental implants were used. The samples were characterized by their roughness, wettability, surface energy, residual stresses, and fatigue behavior. The implants were implanted in minipigs for 4 and 12 weeks. The animals were sacrificed, and histological studies were carried out to determine the osseointegration parameters for each of the implantation times. Ti and ZrO2 dental implants have very similar wettability and surface energy properties. However, the roughness causes a decrease in the hydrophilic character and a decrease of the total surface energy and especially the dispersive component, while the polar component is higher. Due to the compressive residual stresses of alumina sandblasting, the rough dental implant has the best fatigue behavior, followed by Ti and due to the lack of toughness and rapid crack propagation the ZrO2 implants have the worst fatigue behavior. The bone index contact (BIC) values for 4 weeks were around 25% for Ti, 32% for ZrO2, and 45% for Ti-R. After 12 weeks the Ti dental implants increased to 42%, for Ti, 43% for ZrO2, and an important increase to 76% was observed for Ti-R implants. In vivo results showed that the key factor that improves osseointegration is roughness. There was no significant difference between ZrO2 and Ti implants without sandblasting. info:eu-repo/semantics/publishedVersion

A lack of primary stability and osteointegration in metallic implants may result in implant loosening and failure. Adding porosity to metallic implants reduces the stress shielding effect and improves implant performance, allowing the surrounding bone tissue to grow into the scaffold. However, a bioactive surface is needed to stimulate implant osteointegration and improve mechanical stability. In this study, porous titanium implants were produced via powder sintering to create different porous diameters and open interconnectivity. Two strategies were used to generate a bioactive surface on the metallic foams: (1) an inorganic alkali thermochemical treatment, (2) grafting a cell adhesive tripeptide (RGD). RGD peptides exhibit an affinity for integrins expressed by osteoblasts, and have been reported to improve osteoblast adhesion, whereas the thermochemical treatment is known to improve titanium implant osseointegration upon implantation. Bioactivated scaffolds and control samples were implanted into the tibiae of rabbits to analyze the effect of these two strategies in vivo regarding bone tissue regeneration through interconnected porosity. Histomorphometric evaluation was performed at 4 and 12 weeks after implantation. Bone-to-implant contact (BIC) and bone in-growth and on-growth were evaluated in different regions of interest (ROIs) inside and outside the implant. The results of this study show that after a long-term postoperative period, the RGD-coated samples presented higher quantification values of quantified newly formed bone tissue in the implant’s outer area. However, the total analyzed bone in-growth was observed to be slightly greater in the scaffolds treated with alkali thermochemical treatment. These results suggest that both strategies contribute to enhancing porous metallic implant stability and osteointegration, and a combination of both strategies might be worth pursuing. info:eu-repo/semantics/publishedVersion

Articles on the prevalence of peri-implant diseases showed that 90% of peri-implant tissues had some form of inflammatory response and a prevalence of peri-implantitis from 28% to 51% according to various publications. Objective: To provide an overview of how risk factors can be related with peri-implantitis. Methods: A retrospective longitudinal study including 555 implants placed in 132 patients was evaluated based on the presence of peri-implantitis following the criteria of Renvert et al. 2018. Results: In total, 21 patients (15.9%) suffered peri-implantitis (PPG) and 111 patients (84.1%) did not suffer peri-implantitis (NPG). The results reveal that smokers have a high incidence of peri-implantitis (72.7%) compared to non-smokers (27.3%) (p < 0.0005). Another variable with significant results (p < 0.01) was periodontitis: 50% PPG and 23.9% NPG suffered advanced periodontitis. Systemic diseases such as arterial hypertension, diabetes mellitus, osteoporosis, and cardiovascular diseases do not show a statistically significant influence on the incidence of peri-implantitis. Patients who did not attend their maintenance therapy appointment had an incidence of peri-implantitis of 61.4%, compared to 27.3% in those who attend (p < 0.0001). From the results obtained, we can conclude that relevant factors affect peri-implantitis, such as tobacco habits, moderate and severe periodontitis, and attendance in maintenance therapy. info:eu-repo/semantics/publishedVersion

The application of porous materials is increasingly being used in orthopaedic surgery due to its good results. Bone growth within the pores results in excellent mechanical fixation with the bone, as well as good bone regeneration. The pores, in addition to being colonised by bone, produce a decrease in the modulus of elasticity that favours the transfer of loads to the bone. This research shows the results of an experimental study where we have created critical osteoperiosteal defects of 10 mm on rabbit’s radius diaphysis. In one group of 10 rabbits (experimental group) we have implanted a bioactive porous titanium cylinder, and in another group we have allowed spontaneous regeneration (control group). Mechanical tests were performed to assess the material. Image diagnostic techniques (X-ray, scanner and 3D scan: there are no references on the literature with the use of CT-scan in bone defects) and histological and histomorphometric studies post-op and after 3, 6 and 12 months after the surgery were performed. All the control cases went through a pseudoarthrosis. In 9 of the 10 cases of the experimental group complete regeneration was observed, with a normal cortical-marrow structure established at 6 months, similar to normal bone. Titanium trabecular reached a bone percentage of bone inside the implant of 49.3% on its surface 3 months post-op, 75.6% at 6 months and 81.3% at 12 months. This porous titanium biomaterial has appropriate characteristics to allow bone ingrowth, and it can be proposed as a bone graft substitute to regenerate bone defects, as a scaffold, or as a coating to achieve implant osteointegration. info:eu-repo/semantics/publishedVersion

Objectives. The purpose of this work was to determine the influence of residual alumina after sand blasting treatment in titanium dental implants. This paper studied the effect of alumina on physico-chemical surface properties, such as: surface wettability, surface energy. Osseointegration and bacteria adhesion were determined in order to determine the effect of the abrasive particles. Materials and Methods. Three surfaces were studied: (1) as-received, (2) rough surface with residual alumina from sand blasting on the surface and (3) with the same roughness but without residual alumina. Roughness was determined by white light interferometer microscopy. Surface wettability was evaluated with a contact angle video-based system and the surface free energy by means of Owens and Wendt equation. Scanning electron microscopy equipped with microanalysis was used to study the morphology and determine the chemical composition of the surfaces. Bacteria (Lactobacillus salivarius and Streptococcus sanguinis) were cultured in each surface. In total, 110 dental implants were placed into the bone of eight minipigs in order to compare the osseointegration. The percentage of bone-to-implant contact was determined after 4 and 6 weeks of implantation with histometric analysis. Results. The surfaces with residual alumina presented a lower surface free energy than clean surfaces. The in vivo studies demonstrated that the residual alumina accelerated bone tissue growth at different implantation times, in relation to clean dental implants. In addition, residual alumina showed a bactericidal effect by decreasing the quantity of bacteria adhering to the titanium. Conclusions. It is possible to verify the benefits that the alumina (percentages around 8% in weight) produces on the surface of titanium dental implants. Clinical relevance. Clinicians should be aware of the benefits of sand-blasted alumina due to the physico-chemical surface changes demonstrated in in vivo tests.

Titanium surface is an important factor in achieving osseointegration during the early wound healing of dental implants in alveolar bone. The purpose of this study was to evaluate sandblasted-etched surface implants to investigate the osseointegration. In the present study, we used two different types of sandblasted-etched surface implants, an SLA™ surface and a Nanoblast Plus™ surface. Roughness and chemical composition were evaluated by a white light interferometer microscope and X-ray photoelectron spectroscopy, respectively. The SLA™ surface exhibited the higher values (Ra 3.05 μm) of rugosity compared to the Nanoblast Plus™ surface (Ra 1.78 μm). Both types of implants were inserted in the femoral condyles of ten New Zealand white rabbits. After 12 weeks, histological and histomorphometric analysis was performed. All the implants were osseointegrated and no signs of infection were observed. Histomorphometric analysis revealed that the bone–implant contact % (BIC) ratio was similar around the SLA™ implants (63.74 ± 13.61) than around the Nanoblast Plus™ implants (62.83 ± 9.91). Both implant surfaces demonstrated a favorable bone response, confirming the relevance of the sandblasted-etched surface on implant osseointegration. info:eu-repo/semantics/publishedVersion

Background: Implant dentistry has evolved over time, resulting in better treatment outcomes for both patients and clinicians. The aim of this trial was to test whether the immediate loading of implants with a platform-switching design influences the marginal bone level, compared to four-week loading, after one year of follow-up. Moreover, a comparison of clinical data regarding implant survival, implant stability, and patient-reported outcome measures (PROMs) was conducted. Methods: Klockner® VEGA® implants with a ContacTi® surface were placed in partially edentulous patients in the posterior areas. Group A received an immediately loaded prosthesis (one week) and Group B received an early-loaded prosthesis (four weeks). All abutments were placed at the time of surgery. Radiographic and clinical data were recorded. Results: Twenty-one patients were treated (35 implants). No implants were lost during the study. The final marginal bone level did not show differences between groups. The bone loss at 12 months at the implant level was 0.00 mm for both groups (median). The final implant quotient stability (ISQ) values did not differ between groups (median 73 and 70.25), nor did the other clinical parameters or PROMs. Conclusions: The results suggest that neither of the loading protocols with the implants used influenced the marginal bone level—not the osseointegration rate, clinical conditions, or PROMs. Parcialmente financiado por Klockner y U.I.C. fondos de investigación

[ES] El titanio y sus aleaciones se utilizan en odontología para la fabricación de implantes, prótesis y componentes de prótesis debido a su combinación favorable de mecánica, física y propiedades químicas. En los últimos años, las investigaciones en este sector tan competitivo se han centrado en el desarrollo de nuevas aleaciones debido a la gran prevalencia de periimplantitis en los pacientes que emplean implantes dentales. Se han empezado a estudiar aleaciones de titanio que introducen niobio (Nb), zirconio (Zr) y/o tantalio (Ta). Esta aleación cuaternaria Ti-Nb-Zr-Ta se considera una de las más prometedoras por múltiples razones. La bibliografía se centra sobre todo en su análisis microestructural pero no se encuentran apenas ensayos in vitro. Mediante este trabajo se lleva a cabo una caracterización completa del material. Presenta una microestructura hexagonal compacta que permite la reducción de su módulo elástico y el acercamiento de este al del hueso, a diferencia de lo que ocurre con la aleación tan empleada Ti-6Al-4V, con un valor de módulo elástico que dista mucho del del hueso. Se analiza la caracterización microestructural y mecánica de la aleación Ti-35Nb-7Zr-5Ta (TNZT) para conocer en profundidad sus propiedades. Por su parte, los elementos de esta aleación son biocompatibles y parecen no presentar ningún efecto tóxico. Se realizan ensayos de liberación de iones de la aleación TNZT empleando saliva artificial como electrolito y se comparan, nuevamente, con datos de la aleación de titanio puro (Ti CP) y Ti-6Al-4V. Además, estas salivas que contienen los iones liberados son empleados como medio en contacto con dos líneas celulares: las células madre de pulpa dental humana (hDPSC) y la línea celular MG-63 de osteosarcoma humano. De este modo, se analiza la posible citotoxicidad de estas y se mide el grado de viabilidad celular que presentan. Otro factor que se pretende mejorar con el uso de la aleación TNZT es la relación entre la interfase hueso-implante para promover una futura osteointegración. Así pues, se realizan ensayos de diferenciación osteogénica de las células hDPSC y de las MG-63 como control y de adhesión celular de las mismas sobre discos metálicos de TNZT. De este modo, se hace una caracterización completa de esta aleación cuaternaria, no solo en cuanto a sus propiedades mecánicas sino también en cuanto a su análisis biológico. Finalmente, se concluye que la aleación TNZT presenta grandes resultados en todos los ensayos en los que se han utilizado en contacto con las células. Así pues, mediante este trabajo, se anima a seguir investigando acerca de la aleación TNZT, muy prometedora en el campo biomédico., [CA] El titani i els seus aliatges s'utilitzen en odontologia per a la fabricació d'implants, pròtesis i components de pròtesis degut a la seua combinació favorable de mecànica, física i propietats químiques. En els últims anys, les investigacions en aquest sector tan competitiu s'han centrat en el desenvolupament de nous aliatges degut a la gran prevalença de periimplantitis en els pacients que empren implantes dentals. S'han començat a estudiar aliatges de titani que introduïxen niobi (Nb) , zirconi (Zr) i/o tàntal (Ta). Aquest aliatge quaternari Ti-Nb-Zr-Ta es considera un dels més prometedors per nombroses raons. La bibliografia se centra sobretot en el seu anàlisi microestructural però no es troben quasi assajos in vitro. Per mitjà d'este treball es du a terme una caracterització completa del material. Presenta una microestructura hexagonal compacta que permet la reducció del seu mòdul elàstic i l'acostament d'aquest al de l'os, a diferència del que ocorre amb l'aliatge tan emprat Ti-6Al-4V, amb un valor de mòdul elàstic que dista molt del de l'os. S'analitza la caracterització microestructural i mecànica de l'aliatge Ti35Nb-7Zr-5Ta (TNZT) per a conéixer en profunditat les seues propietats. Per altra banda, els elements d'este aliatge són biocompatibles i sembla no presentar cap efecte tòxic. Es realitzen assajos d'alliberament d'ions de l'aliatge TNZT emprant saliva artificial com a electròlit i es comparen, novament, amb dades de l'aliatge de titani pur (Ti CP) i Ti-6Al-4V. A més, estes salives que contenen els ions alliberats són empleades com a mitjà en contacte amb dos línies cel·lulars: les cèl·lules mare de polpa dental humana (hDPSC) i la línia cel·lular MG-63 d'osteosarcoma humà. D'aquesta manera, s'analitza la possible citotoxicitat d'aquestes i es mesura el grau de viabilitat cel·lular que presenten. Un altre factor que es es pretén millorar amb l'ús de l'aliatge TNZT és la relació entre la interfase os-implant per a promoure una futura osteointegració. Així, doncs, es realitzen assajos de diferenciació osteogènica de les cèl·lules hDPSC i de les MG-63 com a control i d'adhesió cel·lular de les mateixes sobre discs metàl·lics de TNZT. D'aquesta manera, es fa una caracterització completa d'este aliatge quaternari, no sols quant a les seues propietats mecàniques sinó també quant al seu anàlisi biològic. Finalment, es conclou que l'aliatge TNZT presenta grans resultats en tots els assajos en què s'han utilitzat en contacte amb les cèl·lules. Així, doncs, per mitjà d'este treball, s'anima a continuar investigant sobre l'aliatge TNZT, molt prometedor en el camp biomèdic., [EN] Titanium and its alloys are used in dentistry for the manufacture of implants, prosthetics, and prosthetic components due to their favorable combination of mechanical, physical, and chemical properties. In recent years, research in this highly competitive sector has focused on the development of new alloys due to the high prevalence of peri-implantitis in patients using dental implants. Titanium alloys that introduce niobium (Nb), zirconium (Zr) and / or tantalum (Ta) have begun to be studied. This Ti-Nb-Zr-Ta quaternary alloy is considered one of the most promising for multiple reasons. The bibliography focuses mainly on its microstructural analysis, but there are hardly any in vitro tests. Through this project a complete characterization of the material is carried out. It presents a compact hexagonal microstructure that allows the reduction of its elastic modulus and its approach to that of bone, unlike what happens with the widely used Ti-6Al-4V alloy, with an elastic modulus value that is far from the one of the bone. The microstructural and mechanical characterization of the Ti-35Nb-7Zr-5Ta (TNZT) alloy is analyzed to understand its properties in depth. On the other hand, the elements of this alloy are biocompatible and do not seem to present any toxic effect. Ion release tests of the TNZT alloy are performed using artificial saliva as electrolyte and are compared, again, with data from the pure titanium alloy (Ti CP) and Ti-6Al-4V. Furthermore, this saliva containing the released ions are used as a medium in contact with two cell lines: human dental pulp stem cells (hDPSC) and the human osteosarcoma cell line MG-63. In this way, the possible cytotoxicity of these is analyzed and the degree of cell viability they present is measured. Another factor that is intended to improve with the use of the TNZT alloy is the relationship between the bone-implant interface to promote future osseointegration. Thus, osteogenic differentiation assays of hDPSC and MG-63 cells used as a control and cell adhesion of them on metallic TNZT discs are performed. In this way, a complete characterization of this quaternary alloy is made, not only in terms of its mechanical properties but also in terms of its biological analysis. Finally, it is concluded that the TNZT alloy presents great results in all the tests in which it has been used in contact with cells. Thus, through this work, further research is encouraged on the TNZT alloy, which is very promising in the biomedical field.

As immediate loading protocols are becoming more frequent, the primary stability of implants has become an essential criterion for the osseointegration of dental implants. Based on this, the objective of this study was to understand the influence of different undersized surgical preparation sites on the insertion torque (IT) and implant stability quotient (ISQ). Four different site-preparation protocols were performed on fresh humid type III bovine bone: one control, the standard protocol recommended by the manufacturer (P1), and three variations of undersized techniques (P2, P3 and P4). The implant used was VEGA by Klockner Implant System. The sample size was n = 40 for each of the four groups. A torquemeter was used to measure the IT, and the ISQ was measured with a Penguin RFA. Both variables showed a tendency to increase as the preparation technique was reduced, although not all the values were statistically significant (p &lt, 0.05) when comparing with the standard preparation. The preparations without a cortical drill, P2 and P4, showed better results than those with a cortical drill. Given the limitations of this study, it can be concluded that reducing the implant preparation can increase both the IT and ISQ. Removing the cortical drill is an effective method for increasing implant stability, although it should be used carefully.

Post-operative therapy for joint replacement is often performed to optimize bone volume and bone-implant contact. Methods, such as pulsed therapeutic ultrasound, have been shown to be a valuable addition to regular physiotherapy to increase bone regeneration. To evaluate the efficacy of kilohertz-frequency (kHz) resonant stimuli to additively manufactured implant analogues, Saos-2 cells were seeded onto porous stainless steel scaffolds and flat substrates. Resonant frequency modes were mapped in the low kHz range, and cells were subjected to daily stimulus for 10 min at a frequency of 1.278 kHz. kHz-frequency excitation was found to increase normalized alkaline phosphatase production by almost twofold on metallic substrates relative to non-vibrated control scaffolds, while peak velocity influenced alkaline phosphatase production on porous scaffolds but not flat substrates. Total cell proliferation was downregulated by excitation, and all excited samples displayed larger variability. This work indicates that vibration within the range of 0.16–0.48 mm/s may reduce cell proliferation, but favour osteogenic gene expression. This study highlights the potential of using kHz-resonance therapy to mitigate early-onset pore occlusion to achieve uniform osseointegration through porous metallic scaffolds.

The purpose of this research is to study the biomechanical response of dental implants in bone-level type locations, 0.5 mm above and below the bone level. In addition, the influence of the thickness of the cortical bone on osseointegration is determined due to the mechanical loads transfer from the dental implant to the cortical and trabecular bone. The thicknesses studied were 1.5 mm and 2.5 mm. Numerical simulations were performed using a finite element method (FEM)-based model. In order to verify the FEM model, the in silico results were compared with the results obtained from a histological analysis performed in an in vivo study with 30 New Zealand rabbits. FEM was performed using a computerized 3D model of bone-level dental implants inserted in the lower jawbone with an applied axial load of 100 N. The analysis was performed using different distances from the bone level and different thicknesses of cortical bone. The interface area of bone growth was evaluated by analyzing the bone–implant contact (BIC), region of interest (ROI) and total bone area (BAT) parameters obtained through an in vivo histological process and analyzed by scanning electron microscopy (SEM). Bone-level implants were inserted in the rabbit tibiae, with two implants placed per tibia. These parameters were evaluated after three or six weeks of implantation. FEM studies showed that placements 0.5 mm below the bone level presented lower values of stress distribution compared to the other studied placements. The lower levels of mechanical stress were then correlated with the in vivo studies, showing that this position presented the highest BIC value after three or six weeks of implantation. In this placement, vertical bone growth could be observed up the bone level. The smallest thickness of the study showed a better transfer of mechanical loads, which leads to a better osseointegration. In silico and in vivo results both concluded that the implants placed 0.5 mm below the cortical bone and with lower thicknesses presented the best biomechanical and histological behavior in terms of new bone formation, enhanced mechanical stability and optimum osseointegration. info:eu-repo/semantics/publishedVersion

En los últimos años, la ciencia de los biomateriales aplicada a los sustitutos óseos se ha centrado en la investigación de nuevos implantes elaborados con materiales que, además de presentar una estructura de poros interconectados esencial para un adecuado crecimiento óseo que asegure el anclaje del implante, presenten también unas óptimas propiedades biomecánicas. Los estudios más recientes se centran en el desarrollo de implantes a base de metales porosos bioactivos, como el titanio, que presentan buenas propiedades mecánicas al soportar adecuadamente las condiciones de carga. Diversos estudios han demostrado que el titanio presenta una buena biocompatibilidad y una alta resistencia a la corrosión, además de unas excelentes propiedades mecánicas, convirtiéndolo, por tanto, en el metal de elección para los implantes. Con el objetivo de estimular la osteointegración, estos implantes de titanio porosos se pueden someter a diversos procesos fisicoquímicos, entre ellos los tratamientos termoquímicos o los tratamientos peptídicos. El tratamiento de los implantes de titanio con un recubrimiento peptídico es una opción extremadamente novedosa basada en el hecho que determinados péptidos fijados a la superficie del titanio pueden mimetizar la parte orgánica del hueso y mejorar así la neoformación ósea en la superficie del implante, mejorando su osteointegración y, finalmente, asegurando un mejor y más prematuro anclaje del implante sobre el hueso. El interés y demanda creciente de la aplicación de implantes de titanio tanto en odontología como en traumatología humana y veterinaria, así como la falta de estudios clínicos comparativos acerca de la respuesta biológica del hueso a los implantes de titanio tratados con los métodos descritos anteriormente, justifica la necesidad de explorar esta línea de investigación y llevar a cabo estudios experimentales que confirman los resultados preliminares obtenidos in vitro. En esta tesis doctoral se llevó a cabo un estudio experimental in vivo mediante la implantación de cilindros de titanio poroso bioactivos en tibias de conejos. Para ello, se elaboraron implantes de titanio poroso de elevada interconexión mediante sinterización en polvo con diferentes diámetros de poro y una interconectividad abierta. Posteriormente, algunos implantes fueron sometidos a tratamientos bioactivos, creando así 3 grupos de tratamiento: termoquímico, peptídico o sin tratamiento bioactivador. Para la implantación ortotópica se intervinieron 18 conejos neozelandeses blancos adultos a los cuales se les practicó un defecto de 3,5mm en la zona medial de la tuberosidad tibial de cada extremidad y se les insertó de forma aleatoria un implante distinto. La evolución de la osteointegración y osteoconducción de los implantes fue evaluada de manera clínica, radiográfica y mediante microscopia electrónica de retrodispersión (MER) con un sistema cuantitativo y cualitativo, en dos bloques de tiempo de 4 y 12 semanas respectivamente. Los resultados demostraron que a nivel cuantitativo la bioactivación de los implantes de titanio mediante el innovador tratamiento peptídico utilizado no produjo, a pesar de los mejores resultados observados, diferencias estadísticamente significativas en cuanto a la respuesta osteoregenerativa in vivo en comparación con la del grupo control y la del grupo termoquímico. En cambio, desde un punto de vista cualitativo, la bioactivación de los implantes de titanio mediante el nuevo tratamiento peptídico utilizado en este estudio generó una respuesta osteoregenerativa con una mayor cantidad y madurez del tejido óseo neoformado en comparación con las del grupo térmico-químico y control, sin embargo, en la zona más interna del implante, la citada mayor neoformación ósea no mostraba contacto íntimo con el metal. In recent years, the science of biomaterials and the search for bone substitutes has focused on the investigation of new implants made from materials that not only provide optimal biomechanical properties, but also present an interconnected pore structure, which greatly ensures the integration of the implant, essential for adequate bone growth. The most recent studies focus on the development of implants based on bioactive porous metals, such as titanium, which present valuable mechanical properties as they adequately withstand loading conditions. Moreover, several studies have shown that titanium presents good biocompatibility, high resistance to corrosion and excellent mechanical properties, therefore making it the metal of choice for musculoskeletal implants. In order to stimulate osteointegration, these porous titanium implants can undergo various physicochemical processes, including thermochemical or peptide treatments. The treatment of titanium implants with a peptide coating is an extremely novel option based on the theory that certain peptides attached to the surface of the titanium can mimic the organic component of the bone and thus improve bone neoformation on the surface of the implant, consequently improving its osteointegration and finally, ensuring a better and faster incipient anchorage of the implant on the bone surface. The growing interest and demand for the application of titanium implants in both human and veterinary orthopedics and dentistry, as well as the lack of comparative clinical studies regarding the biological response of bone to titanium implants treated with the methods described above, justifies the need to explore this line of research and carry out experimental studies that confirm the preliminary results obtained in vitro. In this doctoral thesis an in vivo experimental study was carried out through the implantation of bioactive porous titanium cylinders in the tibiae of rabbits. Briefly, porous titanium implants of high interconnection were prepared by powder sintering with different pore diameters and an open interconnectivity. Subsequently, some implants underwent surface bioactivation, thus creating 3 implant surface treatment groups: thermochemical implant surface treatment, peptide implant surface treatment and a group with no implant bioactivating treatment. For orthotopic implantation, 18 adult white New Zealand rabbits were intervened, a 3.5 mm defect was created in the medial aspect of the tibial tuberosity of each limb and different implants were press-fitted into the bony defects, according to randomly assigned and previously described implant treatment groups. The evolution of the osteointegration and osteoconduction of the implants was evaluated clinically, radiographically and by backscattered scanning electron microscopy (BS-SEM) with a quantitative and qualitative system, in two-time cohorts of 4 and 12 weeks respectively. On the one hand, despite having observed improvements, from a quantitative point of view, the bioactivation of titanium implants with peptide treatment showed no statistically significant differences regarding the osteoregenerative response in vivo, in comparison to the one of the control and the thermochemical group. On the other hand, from a qualitative point of view, the bioactivation of titanium implants through the new peptide treatment used in this study generated an osteoregenerative response with a higher quantity and maturity degree of newformed bone compared to those of the thermal-chemical and control groups. However, in the innermost area of the implant, the aforementioned bone neoformation consistently lacked intimate attachment to the metal surface.

Interaction between the surface of implants and biological tissues is a key aspect of biomaterials research. Apart from fulfilling the non-toxicity and structural requirements, synthetic materials are asked to direct cell response, offering engineered cues that provide specific instructions to cells. This work explores the functionalization of titanium with integrin-binding peptidomimetics as a novel and powerful strategy to improve the adhesion, proliferation and differentiation of osteoblast-like cells to implant materials. Such biomimetic strategy aims at targeting integrins alpha v beta 3 and alpha 5 beta 1, which are highly expressed on osteoblasts and are essential for many fundamental functions in bone tissue development. The successful grafting of the bioactive molecules on titanium is proven by contact angle measurements, X-ray photoelectron spectroscopy and fluorescent labeling. Early attachment and spreading of cells are statistically enhanced by both peptidomimetics compared to unmodified titanium, reaching values of cell adhesion comparable to those obtained with full-length extracellular matrix proteins. Moreover, an increase in alkaline phosphatase activity, and statistically higher cell proliferation and mineralization are observed on surfaces coated with the peptidomimetics. This study shows an unprecedented biological activity for low-molecular-weight ligands on titanium, and gives striking evidence of the potential of these molecules to foster bone regeneration on implant materials. (c) 2015 Elsevier B.V. All rights reserved.

[EN] Implant dentistry has become an important event for people. However, waiting times of processes associated witch this surgery are still long. Nowadays it affects investigate by this way, finding ways to deal with these implants, whether dental, trauma surgery, etc., which can accelerate osseointegration. This project aims to study how it can affect a coating with hydroxyapatite microdomains dental implants in adhesion, cell proliferation and differentiation. In several studies this coating has been deposited from the proposal of Kokubo on polymers and cellulose, corroborating that facilitates the adhesion and cell proliferation. Once studied the times of hydroxyapatite coating on the material used in this work, based on titanium alloy (Ti6Al4V), four times of coating for subsequent assays were determined: 96, 192 and 288 hours and time control (uncoated). Dental pulp mesenchymal cells where seeded on these surfaces, and adhesion, cell proliferation and differentiation were studies using histological techniques (DAPI, eosin staining and rhodamine phalloidin staining); cellular morphology from images taken by scanning electron microscope was also determined. For adhesion, cell culture time was 6 hours, resulting in shorter times than hydroxyapatite coating (96 hours), the adhesion of cells on the coated titanium alloy was important. To study cell proliferation, a 7 days culture was performed. The cells tended to detach from the surface of the coating over time, and those that had been deposited on “cauliflower” hydroxyapatite, proliferated in them, forming large cell clusters. Finally, it was preferred not cause differentiation, but if studied hydroxyapatite itself allowed differentiation of the plated cells to osteoblasts. The cell culture was maintained 15 days, but the results showed no differentiation., [ES] La implantología dental se ha convertido en un hecho importante para las personas. No obstante, los tiempos de espera de los procesos que conlleva esta cirugía aún son largos. Hoy en día se incide en investigar por esta vía, encontrándose formas para tratar estos implantes, ya sean dentales, para cirugía traumática, etc., que puedan acelerar su osteointegración. Este proyecto pretende estudiar cómo puede afectar un recubrimiento con microdominios de hidroxiapatita sobre implantes dentales en la adhesión, proliferación y diferenciación celulares. Se ha visto en bibliografía que la hidroxiapatita es osteoinductiva. En diversos estudios se ha depositado a partir de la propuesta de Kokubo sobre polímeros y celulosa, corroborándose que facilita la adhesión y proliferación celulares. Una vez estudiados los tiempos de recubrimiento de hidroxiapatita sobre el material utilizado en este trabajo, una aleación basada en titanio (Ti6Al4V), se determinaron cuatro tiempos de recubrimiento para los ensayos posteriores: 96, 192 y 288 horas y un tiempo control (sin recubrimiento). Se sembraron células mesenquimales de pulpa dentaria sobre estas superficies y se estudiaron la adhesión, proliferación y diferenciación celulares, a partir de técnicas histológicas (DAPI, tinción por eosina y tinción por rodamina faloidina); también se determinó la morfología celular a partir de imágenes tomadas al microscopio electrónico de barrido. Para la adhesión, el tiempo de cultivo celular fue de 6 horas, obteniéndose como resultado que a tiempos cortos de recubrimiento con hidroxiapatita (96 horas), la adhesión de las células sobre la aleación de titanio recubierta era importante. Para estudiar la proliferación celular, se realizó un cultivo de 7 días. Las células tendían a despegarse de la superficie del recubrimiento a lo largo del tiempo, y aquéllas que se habían depositado sobre las “coliflores” de hidroxiapatita, proliferaban en ellas, formándose grandes cúmulos celulares o clusters. Finalmente, se prefirió no provocar la diferenciación, sino estudiar si la hidroxiapatita por sí misma permitía la diferenciación de las células sembradas a osteoblastos. El cultivo celular se mantuvo 15 días, pero los resultados obtenidos no demostraron una diferenciación celular., [CA] La implantologia dental ha esdevingut un fet important per a les persones. No obstant, els temps d’espera dels processos que porta esta cirurgia encara són llargs. Hui en dia s’incideix en investigar per esta via, trobant-se formes de tractar estos implants, ja siguen dentals, per a cirurgia traumàtica, etc., que poden accelerar la seua osteointegració. Este projecte pretén estudiar com pot afectar un recobriment amb microdominis d’hidroxiapatita sobre els implants dentals en l’adhesió, proliferació i diferenciació cel·lulars. S’ha vist a bibliografia que la hidroxiapatita és osteoinductiva. En diversos estudis s’ha depositat a partir de la proposta de Kokubo sobre polímers i cel·lulosa, corroborant-se que facilita l’adhesió i proliferació cel·lulars. Una vegada estudiats els temps de recobriment d’hidroxiapatita sobre el material utilitzat en este treball, una aleació basada en titani (Ti6Al4V), es varen determinar quatre temps de recobriment per als assajos posteriors: 96, 192 i 288 hores i un temps control (sense recobriment). Es varen sembrar cèl·lules mesenquimals de pulpa dentària sobre estes superfícies i es varen estudiar l’adhesió, proliferació i diferenciació cel·lulars, a partir de tècniques histològiques (DAPI, tinció amb eosina i tinció per rodamina faloidina); també es va determinar la morfologia cel·lular a partir d’imatges preses al microscopi electrònic de rastreig. Per a l’adhesió, el temps de cultiu cel·lular va ser de 6 hores, obtenint-se com resultat que a temps curts de recobriment amb hidroxiapatita (96 hores), l’adhesió de les cèl·lules sobre l’aleació de titani recoberta era important. Per a estudiar la proliferació cel·lular, es va realitzar un cultiu de 7 dies. Les cèl·lules tendien a desapegar-se de la superfície del recobriment al llarg del temps, i aquelles que s’havien depositat sobre les “coliflors” d’hidroxiapatita, proliferaven en elles, formant-se grans cúmuls cel·lulars o clusters. Finalment, es va preferir no provocar la diferenciació, sinó estudiar si la hidroxiapatita per si mateixa permetia la diferenciació de les cèl·lules sembrades a osteoblasts. El cultiu cel·lular es va mantindre 15 dies, però els resultats obtinguts no varen demostrar una diferenciació cel·lular.

Surface modification stands out as a versatile technique to create instructive biomaterials that are able to actively direct stem cell fate. Chemical functionalization of titanium has been used in this work to stimulate the differentiation of human mesenchymal stem cells (hMSCs) into the osteoblastic lineage, by covalently anchoring a synthetic double-branched molecule (PTF) to the metal that allows a finely controlled presentation of peptidic motifs. In detail, the effect of the RGD adhesive peptide and its synergy motif PHSRN is studied, comparing a random distribution of the two peptides with the chemically-tailored disposition within the custom made synthetic platform, which mimics the interspacing between the motifs observed in fibronectin. Contact angle measurement and XPS analysis are used to prove the efficiency of functionalization. We demonstrate that, by rationally designing ligands, stem cell response can be efficiently guided towards the osteogenic phenotype: In vitro, PTF-functionalized surfaces support hMSCs adhesion, with higher cell area and formation of focal contacts, expression of the integrin receptor α5β1 and the osteogenic marker Runx2, and deposition a highly mineralized matrix, reaching values of mineralization comparable to fibronectin. Our strategy is also demonstrated to be efficient in promoting new bone growth in vivo in a rat calvarial defect. These results highlight the efficacy of chemical control over the presentation of bioactive peptides; such systems may be used to engineer bioactive surfaces with improved osseointegrative properties, or can be easily tuned to generate multi-functional coatings requiring a tailored disposition of the peptidic motifs. Statement of significance Organic coatings have been proposed as a solution to foster osseointegration of orthopedic implants. Among them, extracellular matrix-derived peptide motifs are an interesting biomimetic strategy to harness cell-surface interactions. Nonetheless, the combination of multiple peptide motifs in a controlled manner is essential to achieve receptor specificity and fully exploit the potentiality of synthetic peptides. Herein, we covalently graft to titanium a double branched molecule to guide stem cell fate in vitro and generate an osseoinductive titanium surface in vivo. Such synthetic ligand allows for the simultaneous presentation of two bioactive motifs, thus is ideal to test the effect of synergic sequences, such as RGD and PHSRN, and is a clear example of the versatility and feasibility of rationally designed biomolecules.

In this work, we analysed 56 clinically failed and retrieved implants by means of scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and histological studies. The surface contamination was compared to that of unused control implants and with that of the same implants after cleaning in a basic medium. The surfaces of the unused implants presented considerable contamination. In particular, high levels of carbon were detected. The nature of this C was elucidated by XPS analysis of the lubricant used in the machining process. The same contamination was observed in the retrieved implants. Histological studies were carried out by means of light microscopy. Fibrosis and granulomatous lesions were detected in the tissues. XPS analysis indicated the presence of traces of other elements (Na, Ca, Zn, S, F, etc.) that were not related to impurities in cpTi. We examined a cleaning process in a basic medium that eliminates the organic components of the implant surfaces. The cleaned implants were implanted in the patients and the results were excellent. None of the implants failed in following 7 months.

Self-drilling orthodontic mini-implants can be used as temporary devices for orthodontic treatments. Our main goal was to evaluate surface characteristics, roughness and wettability, of surface modified mini-implants to increase their stability during orthodontic treatment without inducing bone fracture and tissue destruction during unscrewing.; Modified mini-implants by acid etching, grit-blasting and its combination were implanted in 20 New Zealand rabbits during 10 weeks. After that, the bone-to-implant (BIC) parameter was determined and the torque during unscrewing was measured. The surface characteristics, roughness and wettability, were also measured, onto modified Ti c.p. discs.; Acid-etched mini-implants (R (a) a parts per thousand 1.7 mu m, contact angle (CA) a parts per thousand 66A degrees) significantly improved the bone-to-implant parameter, 26 %, compared to as-machined mini-implants (R (a) a parts per thousand 0.3 mu m, CA a parts per thousand 68A degrees, BIC = 19 %) due to its roughness. Moreover, this surface treatment did not modify torque during unscrewing due to their statistically similar wettability (p > 0.05). Surface treatments with higher roughness and hydrophobicity (R (a) a parts per thousand 4.5 mu m, CA a parts per thousand 74A degrees) lead to a greater BIC and to a higher removal torque during unscrewing, causing bone fracture, compared to as-machined mini-implants.; Based on these in vivo findings, we conclude that acid-etching surface treatment can support temporary anchoring of titanium mini-implants.; This treatment represents a step forward in the direction of reducing the time prior to mini-implant loading by increasing their stability during orthodontic treatment, without inducing bone fracture and tissue destruction during unscrewing. info:eu-repo/semantics/acceptedVersion

The present work is a revision of the processes occurring in osseointegration of titanium dental implants according to different types of surfaces -namely, polished surfaces, rough surfaces obtained from subtraction methods, as well as the new hydroxyapatite biomimetic surfaces obtained from thermochemical processes. Hydroxyapatite’s high plasma-projection temperatures have proven to prevent the formation of crystalline apatite on the titanium dental implant, but lead to the formation of amorphous calcium phosphate (i.e., with no crystal structure) instead. This layer produce some osseointegration yet the calcium phosphate layer will eventually dissolve and leave a gap between the bone and the dental implant, thus leading to osseointegration failure due to bacterial colonization. A new surface -recently obtained by thermochemical processes- produces, by crystallization, a layer of apatite with the same mineral content as human bone that is chemically bonded to the titanium surface. Osseointegration speed was tested by means of minipigs, showing bone formation after 3 to 4 weeks, with the security that a dental implant can be loaded. This surface can be an excellent candidate for immediate or early loading procedures. Key words:Dental implants, implants surfaces, osseointegration, biomimetics surfaces.

Los cementos de fosfato de calcio son biomateriales utilizados para la regeneración ósea. En esta tesis doctoral se estudia la influencia de la microestructura y la macroporosidad en el comportamiento biológico de un cemento de fosfato de calcio. En la primera parte, se caracterizaron las propiedades físico-químicas y superficiales de dos sustratos de apatita deficiente en calcio con diferente microestructura obtenidos a partir de un cemento de fosfato de calcio (CPC) cuyo principalmente componente es el fosfato tricálcico en fase $\alpha$. % con dos distribuciones de tamaño de partícula distintos. Se estudió la influencia de la microestructura en el comportamiento celular y la adsorción de proteínas como la albúmina, la fibronectina y la lisozima. El uso de dos agentes desorción (EDTA y SDS) permitió evidenciar la influencia de la morfología y tamaño de los cristales de apatita en la fuerza de adhesión de las proteínas estudiadas. Los cultivos celulares con la línea MG-63 mostraron el efecto de la microestructura y el intercambio iónico sobre la proliferación celular. Se observó asimismo una estimulación en la diferenciación celular en uno de los sustratos que fue atribuido a un efecto de la topografía. En la segunda parte, se desarrolló un cemento macroporoso inyectable para aplicaciones médicas, utilizando como agente espumante una solución proteica de albumen. Se optimizó la obtención de la macroporosidad a partir de variables como: la distribución del tamaño de partícula, la relación entre la fase sólida y la fase líquida, la cantidad de agente espumante y la adición de un agente de cohesión como el alginato de sodio para posibilitar su inyección directa en el lugar de implantación. Por último, se demostró mediante estudios \emph{in vivo} en fémur de conejos un mayor potencial de regeneración ósea por parte del cemento macroporoso en comparación con su homólogo microporoso, al obtenerse una mayor cantidad de tejido óseo y una mayor reabsorción en el cemento macroporoso.

El objetivo de este estudio experimental es evaluar si la gammagrafía ósea (GO) es un método válido para cuantificar la actividad metabólica ósea que se produce alrededor de diferentes superficies implantarias durante el proceso de oseointegración "in vivo", y establecer si existe relación entre el nivel de actividad gammagráfica y el porcentaje de contacto hueso-implante. Material y Método: Se han utilizado 12 conejos New Zealand White a los que se colocaron un total 24 implantes MkIII (Nobel Biocare, Goteborg, Suecia), 12 de superficie mecanizada y 12 de superficie TiUnite®, uno tibial y uno femoral en cada animal de forma aleatoria. Preoperatoriamente y en intervalos de 15, 45, 75, 105 días del postoperatorio se realizaron exploraciones mediante GO (planar y con colimador "pinhole") con Tc99MDF (185 mBq) calculándose unos Índices de Actividad gammagráfica (IA= actividad área de estudio/ actividad área control) de las zonas en las que se localizaban los implantes. Se obtuvieron 240 índices de actividad que se relacionaron con las variables: tiempo, tipo de superficie y sus posibles interacciones. Cuando los IA registrados presentaron una cifra semejante a la que mostraban en las GO preoperatorias se procedió a eutanasiar los animales y se procesaron los especimenes según el protocolo de laboratorio con el fin de calcular los porcentajes de contacto hueso-implante mediante Microscopio Electrónico de Barrido (MEB) calculando las correlaciones entre IA y porcentaje de contacto para las dos superficies estudiadas. Los 240 AI fueron procesados estadísticamente para evaluar los resultados (SAS® v8.0 for windows, SAS Institute Inc., Cary, EE.UU.) con un α= 5%. Resultados: - Existe mayor actividad ósea, independientemente de la localización anatómica (tibial o femoral), alrededor de los implantes mecanizados en la primera GO posoperatoria (p=0.0260 pinhole, p=0.0375 planar).- El valor máximo en todos los casos se registró en la primera GO postoperatoria declinando gradualmente, con lo que registra una curva cuya morfología (independientemente de la localización anatómica y el tipo de superficie) se repite en todos los animales de estudio.- La actividad globalmente evaluada fue menor a nivel tibial independientemente de la superficie (p=0.0001).- Comparando el porcentaje de contacto en la interfase hueso-implante al final del estudio, no se observaron diferencias estadísticamente significativas. - La correlación entre la mayor actividad gammagráfica y el porcentaje de contacto solo pudo ser evidenciada entre la superficie mecanizada y los IA obtenidos en la exploración realizada con "pinhole". Discusión:La GO es un método utilizado para evaluar la actividad osteoblástica y por lo tanto la aplicación en implantología puede ser útil, como han demostrado otros autores. En nuestro studio ha sido efectiva para comparer la actividad generada por los dos tipos de superficie implantológicas, encontrándose que la mayor actividad no se correlaciona con la superficie más bioactive (TiUnite®) ni con un mayor porcentaje de contacto óseo analizado mediante MEB a los 3 meses. Este aspecto no ha sido nunca estudiado previamente aunque otros autores se han interesado por este método diagnóstico como un medio de estudio de la actividad osteoblástica generada por un implante dental.Este resultado puede ser debido a que la superficie mecanizada crea una mayor reacción inflamatoria añadida al proceso de la oseointegración, o a que se require un mayor trabajo biológico para conseguirla. Se precisan más estudios para confirmar esta hipótesis. Respecto al porcentaje de contacto hueso-implante a los 3 meses no existe diferencia estadísticamente significativa probablemente porque las superficies bioactivas se diferencian más en los casos de baja calidad ósea y en el periodo temprano de la oseointegración pero no cuando este proceso ya ha sido completado. Conclusiones: La GO es un método eficaz para cuantificar la actividad ósea periimplantaria generada por diferentes superficies y permite establecer comparaciones entre ellas. Los porcentajes de contacto óseo se igualan con el tiempo en las dos superficies estudiadas. Solo existe correspondencia entre actividad gammagráfica y porcentaje de contacto para la gammagrafía con colimador pinhole., "Technetium 99-MDP scintigraphy as a method to evaluate osteoblastic activity around implants. Comparison between machined and TiUnite® surfaces in rabbit model".Work hypothesis: 1- the scintigraphy is an approach to study the osseous integration process and allows to differentiate between surfaces biologic response. 2- There is a relation between scintigraphic activity and quantity of bone-implant contact. Materials and Methods: 24 implants (MKIII 10 x 3.75) where installed in 12 New Zealand rabbits, were (12 in femur, 12 in tibia) with different surfaces (machined or TiUnite®). Two kind of scintigraphy (185 mBq of Tc99MDP tracer) were performed one week before the surgery and then every 15 days, 1, 2, 3 months (1 planar and 2 pinhole collimator: 1 in femur, 1 in tibia on the same leg) on each rabbit. AI was calculated (AI= count pixels in implant region/ count in control leg in the same region). When the IA was similar to the baseline, the animals were sacrificed.The 240 AI was processed statistically to evaluate the results (SAS® v8.0 for windows, SAS Institute Inc., Cary, EE.UU.) with an α= 5%. Results:- We found more osseous activity, independent on the anatomic place (tibia or femur), around machined implants in the first post-op scintigraphies (p=0.0260 pinhole, p=0.0375 planar).- Global activity was less in tibia than in femur independent on the surface (p=0.0001).- Comparing the percentage of implant bone contact at the end of the study, there was no statistically difference.Discussion:In our study scintigraphy has been effective to compare the activity generated by two types of implant surfaces, but the results demonstrate that more osseous activity around implant not correlates with a better bioactive surface (TiUnite®) or a major percentage of bone contact analyzed by SEM at 3 months. This aspect never has been studied before even though other authors are interested about this kind of diagnostic technique to study the osteoblastic activity at the implant site.It can be caused because machined surface create greater reaction to foreign body, and more studies must be done to confirm these hypothesis.Respect to the bone-implant percentage there is no statistically differences probably because the bioactive surfaces are better in the poor bone quality and in the early period of osseointegration but not at the end of the process.Conclusions:1- Scintigraphy (planar or pinhole) is a diagnostic technique useful to evaluate metabolic activity around implants in animal model.2- The gammagraphic activity descrives a curve characterized by a significant increase in the first post-op exam, and gradually falloff and returned to pre-implant levels at about 3 months.3- We can consider the duration of the osseointegration process is equivalent to the time that scintigraphy is approximately the same as the pre-op period, and is the same for the two implant surfaces.4- There is no differences respect the time necessary of osseointegration related on location.5- A greater gammagraphyc activity not correlates with a greater percentage of bone-implant contact.

El éxito clínico de los implantes dentales, fabricados en titanio comercialmente puro (Ti c.p.), está basado en la consecución de la osteointegración, es decir, la conexión directa estructural y funcional entre el hueso vivo, ordenado, y la superficie del implante. La mejora de la osteointegración a corto y largo plazo es función de múltiples factores, de entre los cuales, la calidad superficial del implante (fisicoquímica y topográfica) es de gran importancia. De hecho, todas las interacciones biológicas y mecánicas que se dan entre el implante y los tejidos circundantes son a través de la interfaz creada entre dichos tejidos y la superficie del material implantado.En este trabajo se estudian y desarrollan distintos tratamientos aplicados sobre la superficie de los implantes dentales con el objetivo final de obtener implantes con una mejor osteointegración, tanto a corto como a largo plazo. En la primera parte se obtienen superficies rugosas por medio del tratamiento del granallado.La rugosidad de las superficies de Ti c.p. granalladas depende no sólo del tamaño de las partículas abrasivas de proyección empleadas (125 - 300 m; 425 - 600 m; 1000 - 1400 m), sino también de su naturaleza química (Al2O3, SiC, TiO2 y ZrO2) y su forma. Esta rugosidad se debe cuantificar con, al menos, dos parámetros, uno de altura (Ra) y otro de espaciado (Pc). Además, cualquiera que sea la naturaleza química de las partículas empleadas, quedan restos de las mismas sobre las superficies tratadas. Con estas premisas, las propiedades de la superficie del Ti c.p. granallado se han podido optimizar, ya que la respuesta de adhesión y diferenciación de los osteoblastos está influenciada por la rugosidad y la naturaleza de las partículas de proyección. Además, aunque el aumento de rugosidad y las tensiones residuales que se inducen con el granallado influyen sobre el comportamiento electroquímico del material, éste es adecuado con respecto a su resistencia a la corrosión, de acuerdo a su posible utilización como material para la fabricación de implantes dentales.En la segunda parte se obtienen superficies rugosas y bioactivas por medio de un tratamiento en dos pasos: en primer lugar se granalla el implante (con las condiciones óptimas determinadas en la primera parte); y después se aplica un tratamiento termoquímico. El tratamiento termoquímico consiste en atacar el metal con NaOH y obtener en su superficie un gel hidratado de titanato de sodio. Este gel se deshidrata y densifica con un tratamiento térmico a 600 oC. En estas condiciones, el Ti c.p. es bioactivo.Las superficies de Ti c.p. granalladas con Al2O3 y tratadas termoquímicamente, demuestran su potencial bioactividad porque hacen crecer por vía química in vitro, sobre su superficie, una capa de apatita; y la confirman, al crecer también in vivo. Sin embargo, la presencia de los restos de partículas de SiC sobre la superficie del metal inhibe su bioactividad. Estas superficies rugosas y bioactivas se estudian de forma comparativa, in vitro e in vivo, con otras no rugosas y/o bioinertes. La respuesta de diferenciación de los osteoblastos y la osteointegración a corto y medio plazo se ven favorecidas por la combinación sinérgica de la rugosidad y la bioatividad del metal. Como consecuencia, los implantes rugosos y bioactivos son candidatos preferenciales para ser utilizados en los procedimientos clínicos de carga inmediata.