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Screw-bone construct failures are a true challenge in orthopaedic implant fixation, particularly in poor quality bone. Whilst augmentation with polymeric or ceramic bone cement can improve the primary stability of the screws, the cement may block the flow of blood and nutrients and hamper bone remodelling. In this study, soft, non-setting biomaterials based on Hyalectin gels and hydroxyapatite (HA) particles with different morphological parameters were evaluated as potential augmentation materials, using a lapine ex vivo bone model. The pull-out force, stiffness, and work to fracture were considered in evaluating screw attachment. The pull-out force of constructs reinforced with Hyalectin containing irregularly shaped nano-HA and spherically shaped micro-HA particles were found to be significantly higher than the control group (no augmentation material). The pull-out stiffness increased for the micro-HA particles and the work to fracture increased for the irregular nano-HA particles. However, there were no significant augmentation effect found for the spherical shaped nano-HA particles. In conclusion, injectable Hyalectin gel loaded with hydroxyapatite particles was found to have a potentially positive effect on the primary stability of screws in trabecular bone, depending on the HA particle shape and size.

In this work, we propose hydroxyapatite (HA) as a hard template to unlock the porosity of Fe-N-C catalyst materials. Using HA, a naturally occurring mineral that can be removed with nitric acid, in the synthesis generates a catalyst material with a unique porous network comprising abundant pores and interparticle cavities ranging from 10 to 3000 nm. Hard templating with HA alongside ZnCl2 as a micropore former results in a Fe-N-C catalyst based on naturally abundant peat with excellent oxygen reduction activity in alkaline conditions. A half -wave potential of 0.87 V vs RHE and a peak power density of 1.06 W cm-2 were achieved in rotating ring disk electrode and anion exchange membrane fuel cell experiments, respectively, rivaling the performance of other state-of-the-art platinum-free catalysts presented in the literature. A combined approach of using renewable peat as a carbon source and HA as a hard template offers an environmentally friendly approach to high-performance Fe-N-C catalysts with abundant porosity., QC 20240110

Nowadays the bone conditions have been a meaning clinical challenge and solutions are limited, sometimes ineffective. Hydroxyapatite investigation (main bone component) has gained significant importance. In this research, was analyzed the calcium precursor effect on structural and microstructural properties of hydroxyapatite comparing results of hydroxyapatite obtained from a natural source. Through the solution combustion synthesis were synthesized hydroxyapatite powders using calcium carbonate extracted from eggshell and commercial calcium carbonate and calcium nitrate. As well the natural source of hydroxyapatite was bovine bone which was washed, fractured and heat treatment. The functional groups were obtained by infrared spectroscopy and the crystalline phases by X-ray diffraction. Transmission electron microscopy allowed to determine the particle spherical morphology produced from calcium carbonate (eggshell) with the smallest size (∼20-50 nm) while those obtained by commercial precursors presented nonhomogeneous morphology. The results showed that the respective process followed was efficient to get hydroxyapatite nanoparticles obtained from calcium carbonate at temperature of 1100ºC. Calcium carbonate from eggshells allowed getting HAp whose morphology was homogeneous with nanometric size., Debido a que en la actualidad las afecciones óseas siguen siendo un desafío clínico significativo y las soluciones son limitadas y en algunos casos poco efectivas, la investigación alrededor de la hidroxiapatita, principal componente mineral del hueso ha cobrado una importancia relevante.En este trabajo de investigación se analizó el efecto del precursor de calcio en las características estructurales y microestructurales de la hidroxiapatita, comparando los resultados obtenidos con hidroxiapatita extraída de una fuente natural. Mediante el método de reacción por combustión en solución fueron sintetizados polvos de hidroxiapatita utilizando como precursores de calcio carbonato de calcio extraído de la cáscara de huevo y carbonato y nitrato de calcio comerciales. A su vez, la fuente natural de hidroxiapatita fue hueso bovino, que se sometió a un proceso de lavado, fractura y tratamiento térmico. Los grupos funcionales presentes en las muestras obtenidas fueron determinados mediante espectroscopia infrarroja y las fases cristalinas mediante difracción de rayos-X. La microscopía electrónica de transmisión permitió determinar la morfología esférica de las partículas obtenidas a partir de carbonato de calcio (de cáscara de huevo) con el menor tamaño de partícula (entre 20 y 50 nm); mientras que, las obtenidas a partir de precursores comerciales presentaron una morfología no homogénea. Los resultados mostraron que el proceso seguido fue eficiente para la obtención de nanopartículas de hidroxiapatita cuando se obtiene a partir de carbonato de calcio y a una temperatura de 1100ºC. El carbonato de calcio proveniente de la cáscara de huevo permitió obtener hidroxiapatita con morfología homogénea y tamaño nanométrico.

Guided Bone Regeneration (GBR) is the choice of treatment for improving the horizontal and vertical bone volume through bone grafting. GBR membranes work on the principle of preventing epithelial migration into the defect space while maintaining the space for cell migration and differentiation at the defect site. Hydroxyapatite has been commonly used as a bone graft for infrabony defects. The study was conducted at the Department of Biomaterials at Saveetha Dental College. GBR membrane was prepared and its material characterization was done using Scanning Electron Microscope (SEM), Energy Dispersive X-ray (EDX) analysis, Fourier Transform Infrared Radiation (FTIR), and Confocal Analysis. The developed GBR membrane revealed SEM properties conducive to cell attachment. EDX and FTIR analysis showed the successful development of the collagen-gelatin-hydroxyapatite membrane. Cell culture and confocal analysis revealed excellent biocompatibility with a homogenous layer of viable cells. The developed composite GBR membrane is a biogenic membrane with relevant biomineralization potential that should be applied for GBR applications., La regeneración ósea guiada (GBR) es el tratamiento de elección para mejorar el volumen óseo horizontal y vertical mediante injertos óseos. Las membranas GBR funcionan según el principio de prevenir la migración epitelial hacia el espacio del defecto. La hidroxiapatita se ha utilizado habitualmente como injerto óseo para defectos infraóseos. El estudio se realizó en el Departamento de Biomateriales del Saveetha Dental College. Se preparó un scaffold o andamio, el cual se caracterizó mediante microscopio electrónico de barrido (SEM), análisis de rayos X de dispersión de energía (EDAX), radiación infrarroja por transformada de Fourier (FTIR) y análisis confocal. El andamio desarrollado reveló propiedades propicias para la unión celular. Los análisis EDAX y FTIR mostraron el desarrollo exitoso de la membrana de colágeno-gelatina-hidroxiapatita. El cultivo celular y el análisis confocal revelaron una excelente biocompatibilidad con una capa homogénea de células viables. El andamio desarrollado es una membrana biogénica con un potencial de biomineralización relevante que puede utilizarse para aplicaciones GBR.

Objectives This study aimed to evaluate the intensity of the subacute local biological effects after implantation and osseoconductive potential of novel hydroxyapatite-based bone substitute coated with poly (lactide-co-glycolide), named ALBO-OS, in comparison to Bio-Oss®. Methods Fifteen male Wistar rats, randomly assigned into groups: 10, 20, and 30 days (n꞊5), were subcutaneously implanted with ALBO-OS and Bio-Oss®. Furthermore, artificially made bone defects on both rat’s tibias were implanted with experimental materials. Unimplanted defects represented negative control. After the animals’ euthanizing, tissue samples were prepared and analyzed histologically and histomorphometrically. Results Normal healing of the epithelial tissue was observed, with no signs of infection or necrosis. Minimal vascular congestion was noted immediately around the graft, with no signs of tissue oedema, with a minimal capsule thickness. The applied material did not cause an inflammatory response (IR) of significant intensity, and 20 days after implantation, the IR was mainly assessed as minimal. The tibial specimen showed that ALBO-OS has good osseoconductive potential, similar to Bio-Oss®, as well as low levels of acute and subacute inflammation. Conclusions The tested material exhibits satisfying biocompatibility, similar to Bio-Oss®.

This study aimed to compare the biological properties of newly synthesized cements based on calcium phosphate with a commercially used cement, mineral trioxide aggregate (MTA). Strontium (Sr)-, Copper (Cu)-, and Zinc (Zn)-doped hydroxyapatite (miHAp) powder was obtained through hydrothermal synthesis and characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectrometry (EDX). Calcium phosphate cement (CPC) was produced by mixing miHAp powder with a 20 wt.% citric acid solution, followed by the assessment of its compressive strength, setting time, and in vitro bioactivity. Acetylsalicylic acid (ASA) was added to the CPC, resulting in CPCA. Biological tests were conducted on CPC, CPCA, and MTA. The biocompatibility of the cement extracts was evaluated in vitro using human dental pulp stem cells (hDPSCs) and in vivo using a zebrafish model. Antibiofilm and antimicrobial effect (quantified by CFUs/mL) were assessed against Streptococcus mutans and Lactobacillus rhamnosus. None of the tested materials showed toxicity, while CPCA even increased hDPSCs proliferation. CPCA showed a better safety profile than MTA and CPC, and no toxic or immunomodulatory effects on the zebrafish model. CPCA exhibited similar antibiofilm effects against S. mutans and L. rhamnosus to MTA.

Nitrogen and phosphorus pollution is still a serious environmental problem and a major threat to sustainable development, as they mainly cause eutrophication. Therefore, increasingly stricter requirements are placed on wastewater treatment plants when it comes to emissions of nutrients. To meet these requirements, it is important to continuously renew and improve the purification processes, thereby reducing the emissions of nutrients to the sea, lakes, and streams. The effect of simultaneous nitrogen removal and phosphorus recycling was investigated in this study, employing a one-step process for partial nitritation/anammox-hydroxyapatite (PN/HAP). An experiment in a laboratory-scale SBR reactor (Sequence Batch Reactor) was performed using wastewater from the side-stream centrate. This study validated results to a certain extent published studies by other researchers. However, they had almost exclusively used synthetic wastewater, unlike the here presented where real wastewater was used. The innovative PN/A-HAP process showed effective nitrogen and phosphorus removal without additional aeration or pH adjustment, which means lower energy consumption, reduced nitrous oxide emissions, and reduced sludge production. The results showed an average nitrogen removal efficiency of 32.84% and an average phosphorus removal efficiency of 71.48%. These results indicate significant potential for sustainable wastewater management for some nitrogen and phosphorus side streams at the treatment plants. However, further research is required on a larger scale to precisely assess the long-term separation efficiency for nitrogen and phosphorus, as well as the scalability and usability of the process under real conditions. This Thesis was performed in the frame of a research project 'Process development of CA-induced HAP (Hydroxyapatite) granulation in nitrogen separation with Anammox' funded by the VA Cluster Mälardalen., Kväve- och fosforföroreningar är fortfarande ett allvarligt miljöproblem och ett stort hot mot en hållbar utveckling, eftersom de främst orsakar övergödning. Därför ställs allt strängare krav på avloppsreningsverken när det gäller utsläpp av näringsämnen. För att uppfylla dessa strängare krav är det viktigt att kontinuerligt förnya och förbättra reningsprocesserna och därigenom minska utsläppen av näringsämnen till hav, sjöar och vattendrag. I denna studie undersöktes effekten av samtidig kväveavskiljning och fosforåtervinning från avloppsvatten med hjälp av en enstegsprocess för partiell nitritering/Anammox-Hydroxyapatit (PN/HAP). Ett experiment i laboratorieskala genomfördes med hjälp av en SBR-reaktor (sequence batch reactor) för behandling av avloppsvatten från sidoströmscentrat. Denna studie validerade delvis resultat från andra forskares publicerade studier.Dessa hade dock nästan uteslutande använt syntetiskt avloppsvatten till skillnad från den här presenterade där riktigt avloppsvatten användes. Den innovativa PN/A-HAP-processen visade effektiv kväve- och fosforavskiljning utan behov av ytterligare luftning eller pH-justering, vilket i praktiken betyder lägre energiförbrukning, minskade lustgasutsläpp och minskad slamproduktion. Resultaten visade en genomsnittlig kväveavskiljningseffektivitet på 32,84% och en genomsnittlig fosforavskiljningseffektivitet på 71,48%. Dessa resultat tyder på en betydande potential för hållbar avloppsvattenhantering för vissa kväve- och fosforrika sidoströmmar vid reningsverken. Det krävs dock ytterligare forskning i större skala för att exakt kunna bedöma den långsiktiga avskiljningseffektiviteten för kväve och fosfor, samt processens skalbarhet och användbarhet under verkliga förhållanden. Denna artikel är skriven som en del av ett forskningsprojekt 'Processutveckling av Ca-inducerad HAP (hydroxyapatit) granulering vid kväveavskiljning med anammox' finansierat av VA-kluster Mälardalen.

The interconnection of three-dimensional (3D) printing, material science, and bone tissue engineering holds immense promise in the realm of scaffold development for bone repair. This work delves into the intricate interplay between various factors influencing the success hydroxyapatite biomaterials in bone regeneration, including material selection, porosity, structural design, surface modification, and other mechanical characteristics. Our aim is the pursuit of ideal biomaterials possessing both favorable biological responses and mechanical integrity. Fourier transform infrared spectroscopy (FTIR) is used to analyze the chemical structure of the material, particularly the chemical bonds present. Using SEM, we were subsequently able to analyze the microstructure and nanostructure of the 3D printed hydroxyapatite sample.

Bacterial cellulose (BC) is a highly pure polysaccharide biopolymer that can be produced by various bacterial genera. Even though BC lacks functional properties, its porosity, three-dimensional network, and high specific surface area make it a suitable carrier for functional composite materials. In the present study, BC-producing bacteria were isolated from kombucha beverage and identified using a molecular method. Two sets of the BC hydrogels were produced in static conditions after four and seven days. Afterwards, two different synthesis pathways were applied for BC functionalization. The first method implied the incorporation of previously synthesized HAp/TiO2 nanocomposite using an immersion technique, while the second method included the functionalization of BC during the synthesis of HAp/TiO2 nanocomposite in the reaction mixture. The primary goal was to find the best method to obtain the functionalized material. Physicochemical and microstructural properties were analyzed by SEM, EDS, FTIR, and XRD methods. Further properties were examined by tensile test and thermogravimetric analysis, and antimicrobial activity was assessed by a total plate count assay. The results showed that HAp/TiO2 was successfully incorporated into the produced BC hydrogels using both methods. The applied methods of incorporation influenced the differences in morphology, phase distribution, mechanical and thermal properties, and antimicrobial activity against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Proteus mirabilis (ATCC 12453), and Candida albicans (ATCC 10231). Composite material can be recommended for further development and application in environments that are suitable for diseases spreading.

Hydroxyapatite-based materials have been widely used in countless applications, such as bone regeneration, catalysis, air and water purification or protein separation. Recently, much interest has been given to controlling the aspect ratio of hydroxyapatite crystals from bulk samples. The ability to exert control over the aspect ratio may revolutionize the applications of these materials towards new functional materials. Controlling the shape, size and orientation of HA crystals allows obtaining high aspect ratio structures, improving several key properties of HA materials such as molecule adsorption, ion exchange, catalytic reactions, and even overcoming the well-known brittleness of ceramic materials. Regulating the morphogenesis of HA crystals to form elongated oriented fibres has led to flexible inorganic synthetic sponges, aerogels, membranes, papers, among others, with applications in sustainability, energy and catalysis, and especially in the biomedical field., This project has received funding from the European Research Council (ERC), grant agreement number 101055053 (BAMBBI). Maria-Pau Ginebra acknowledges the support received through the ICREA Academia Award for excellence in research, funded by the Generalitat de Catalunya. Montserrat Espanol acknowledges the support from Generalitat de Catalunya through the Serra Hunter program, and Anna Diez-Escudero acknowledges the Spanish Ministry of Universities for the support received through the Maria Zambrano fellowship., Peer Reviewed, Postprint (published version)

This study aimed to (1) comparatively analyze properties of Sr- and Mg-substituted hydroxyapatite (HAP)-based dental inserts; (2) evaluate insert bonding to restorative materials, and (3) evaluate the effect of doped HAP inserts on fracture resistance (FR) of human molars with large occlusal restorations. By ion-doping with Sr or Mg, 3 insert types were obtained and characterized using XRD, SEM, Vickers hardness and fracture toughness. Shear bond strength (SBS) was determined between acid etched or unetched inserts and following materials: Maxcem cement (Kerr); Filtek Z250 (3M) bonded with Single Bond Universal (SBU; 3M) or Clearfil Universal (Cf; Kuraray). Modified Class I cavities were prepared in 16 intact molars and restored using insert + composite or composite only (control) (n = 8/group). FR of restored molars was determined by static load until fracture upon thermal cycling. Fracture toughness was similar between Sr/Mg-doped inserts (0.94–1.04 MPam 1/2 p = .429). Mg-doped inserts showed greater hardness (range 4.78–5.15 GPa) than Sr6 inserts (3.74 ± 0.31 GPa; p < .05). SBS for SBU and Cf adhesives (range 7.19–15.93 MPa) was higher than for Maxcem (range 3.07–5.95 MPa) (p < .05). There was no significant difference in FR between molars restored with insert-containing and control restorations (3.00 ± 0.30 kN and 3.22 ± 0.42 kN, respectively; p > .05). HAP-based inserts doped with Mg/Sr had different composition and mechanical properties. Adhesive bonding to inserts resulted in greater bond strength than cementation, which may be improved by insert acid-etching. Ion-doped HAP inserts did not affect FR of restored molars. In conclusion, HAP-based dental inserts may potentially replace dentin in large cavities, without affecting fracture resistance of restored teeth.

The slow advance in anticancer drug development can be attributed to the limitations of conventional models, predominantly monolayer cell (2D) cultures and animal models, which inadequately recapitulate the complex nature of human malignant tumors. Three-dimensional (3D) in vitro models are invaluable tools in drug screening; however, creating a universal model for all cancer types poses challenges due to the diverse nature of cancers. The aim of this work was to develop a single, versatile model using alginate microfibers to accommodate cultivation of various cancer cells.

INTRODUCTION: Tissue engineering strives for innovative solutions in addressing challenges associated with contemporary bone tissue implants. This study focuses on the electrophoretic deposition (EPD) of hydroxyapatite-based bioceramic composites containing antibacterial agents onto titanium surfaces. Two composite coatings, hydroxyapatite/ chitosan (HAP/CS) and hydroxyapatite/chitosan/gentamicin (HAP/CS/Gent) were developed to combat issues such as poor adhesion, limited antibacterial potential, limited bioactivity, and potential toxicity of implant materials [1]. EXPERIMENTAL: EPD was performed at constant voltage (5 V, 12 min) on pure Ti plates from aqueous (HAP/CS and HAP/CS/Gent) suspensions. The uniformity and functionality of the deposited coatings were assessed through comprehensive physico-chemical characterization using X-ray diffraction (XRD) (Philips PW 1710, Netherlands) and scanning electron microscopy (SEM, Hitachi S-4700, J) equipped with energy dispersive X-Ray spectroscopy (EDS, X-Max, Oxford Instruments, UK). Antibacterial activity was evaluated against Staphylococcus aureus TL and Escherichia coli ATCC 25922 by quantitatively monitoring changes in the viable number of bacterial cells in suspension. Cytotoxicity against MRC-5 and L929 cell lines was investigated using trypan blue dye-exclusion test (DET) and MTT assay for assessing cell metabolic activity. Statistical significance was determined for antibacterial and cytotoxicity results by one-way analysis of variance (ANOVA), followed by multiple comparisons post-hoc test. RESULTS AND DISCUSSION: XRD revealed broadened diffraction maximums corresponding to fine HAP crystallites. Porous surface with homogeneously distributed spherical HAP agglomerates embedded in wax-like polymers' matrix of CS was observed for both coatings by SEM. The addition of gentamicin significantly enhanced the antibacterial activity of the HAP/CS/Gent coating – complete reduction of S. aureus bacterial cells was achieved

This dissertation explores the multifaceted roles of rare-earth doped hydroxyapatite in biomedical applications, bridging the gap between luminescence studies and osteogenic potential in the context of bone tissue engineering and regenerative medicine. In the second chapter, we look into the luminescence properties of terbium, cerium, and europium doped hydroxyapatite scaffolds when immersed in simulated body fluid (SBF) over a four-week period. Our comprehensive study reveals a consistent decrease in luminescence emission intensity across all samples, accompanied by a reduction in the concentration of rare-earth ions within the scaffolds, as confirmed by energy dispersive spectroscopy. Furthermore, fluorescence spectroscopy demonstrates the translocation of these ions into the SBF, indicating the scaffolds' partial dissolution over time. The employment of rare-earth ions as luminescence markers offers profound insights into apatite formation mechanisms, presenting significant implications for the development of safer and more durable materials in biomedical applications.Expanding upon the foundational knowledge established in the first and second chapters, the third chapter investigates the osteogenic potential of rare-earth doped hydroxyapatite scaffolds using a murine pre-osteoblastic cell line. This study assesses the effects of ytterbium, terbium, cerium, and europium doping on osteoblast differentiation, gauged by alkaline phosphatase activity and the expression of osteogenic marker genes such as Runx2, OCN, ALP, OPN, and BMP2. Our findings indicate a notable enhancement in differentiation activity with the incorporation of rare-earth elements, with europium and ytterbium doped HAp showing superior performance. Cathodoluminescence spectroscopy further corroborates these results by revealing distinct emission peaks specific to the Eu2+/Eu3+ and Yb2+ ions, underscoring the role of valence state incorporation in augmenting osteoblast differentiation. Collectively

Objectives: To assess and compare the cell viability and ion release profiles of two conventional glass ionomer cements (GICs), Fuji IX and Ketac Molar EasyMix, modified with TiO2 and Mg-doped-HAp nanoparticles (NPs). Methods: TiO2 NPs, synthesized via a sol–gel method, and Mg-doped hydroxyapatite, synthesized via a hydrothermal process, were incorporated into GICs at a concentration of 5 wt.%. The biocompatibility of prepared materials was assessed by evaluating their effects on the viability of dental pulp stem cells (DPSCs), together with monitoring ion release profiles. Statistical analysis was performed using One-way analysis of variance, with significance level p < 0.05. Results: The addition of NPs did not significantly affect the biocompatibility of GICs, as evidenced by comparable decreased levels in cell viability to their original formulations. Distinct variations in cell viability were observed among Fuji IX and Ketac Molar, including their respective modifications. FUJI IX and its modification with TiO2 exhibited moderate decrease in cell viability, while other groups exhibited severe negative effects. While slight differences in ion release profiles were observed among the groups, significant variations compared to original cements were not achieved. Fluoride release exhibited an initial “burst release” within the initial 24 h in all samples, stabilizing over subsequent days. Conclusions: The addition of NPs did not compromise biocompatibility, nor anticariogenic potential of tested GICs. However, observed differences among FUJI IX and Ketac Molar, including their respective modifications, as well as induced low viability of DPSC by all tested groups, suggest the need for careful consideration of cement composition in their biological assessments. Clinical significance: The findings contribute to understanding the complex interaction between NPs and GIC matrices. However, the results should be interpreted recognizing the inherent limitations associated

Objectives: The impact of implant surfaces in dental biofilm development is presently unknown. The aim of this investigation was to assess in vitro the development of a complex biofilm model on titanium and zirconium implant surfaces, and to compare it with the same biofilm formed on hydroxyapatite surface. Methods: Six standard reference strains were used to develop an in vitro biofilm over sterile titanium, zirconium and hydroxyapatite discs, coated with saliva within the wells of pre-sterilized polystyrene tissue culture plates. The selected species used represent initial (Streptococcus oralis and Actinomyces naeslundii), early (Veillonella parvula), secondary (Fusobacterium nucleatum) and late colonizers (Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans). The developed biofilms (growth time 1 to 120h) were studied with confocal laser scanning microscopy using a vital fluorescence technique and with low-temperature scanning electron microscopy. The number (colony forming units/biofilm) and kinetics of the bacteria within the biofilm were studied with quantitative PCR (qPCR). As outcome variables, the biofilm thickness, the percentage of cell vitality and the number of bacteria were compared using the analysis of variance. Results: The bacteria adhered and matured within the biofilm over the three surfaces with similar dynamics. Different surfaces, however, demonstrated differences both in the thickness, deposition of the extracellular polysaccharide matrix as well as in the organization of the bacterial cells. Significance: While the formation and dynamics of an in vitro biofilm model was similar irrespective of the surface of inoculation (hydroxyapatite, titanium or zirconium), there were significant differences in regards to the biofilm thickness and three-dimensional structure., Depto. de Especialidades Clínicas Odontológicas, Fac. de Odontología, TRUE, pub

Hydroxyapatite is a biocompatible material with various applications. To meet the demand for industrial use of this material, a rapid and upscalable process for the synthesis of hydroxyapatite nanoparticles was developed using an in-house developed two-stage continuous flow hydrothermal reactor. In the framework of this study, phase pure and highly crystalline 30 to 115 nm long hydroxyapatite nanorods were produced for potential use as nanofertilizers. The phase composition of the nanorods was confirmed by X-ray diffraction. Particle size and shape were investigated using transmission electron microscopy. Inductively coupled plasma mass spectrometry was used to determine the Ca:P ratio. It was shown that the use of a second mixing stage allows the particle length to be decreased down to 30 nm without compromising on crystallinity. In addition to using different mixing stages, adjusting the pH and controlling the flow speed allow wide range size tuning of the produced particles. The experimental setup allows for continuous synthesis of phase pure and highly crystalline hydroxyapatite nanorods, ensuring the reproducibility and scalability of the process. Dispersive behavior and dissolution in citrate buffer at a hydroponic pH of 5.5 were studied to evaluate further possibilities of applying produced NPs on the plants.

The application of 3D printing to calcium phosphates has opened unprecedented possibilities for the fabrication of personalized bone grafts. However, their biocompatibility and bioactivity are counterbalanced by their high brittleness. In this work we aim at overcoming this problem by developing a self-hardening ink containing reactive ceramic particles in a polycaprolactone solution instead of the traditional approach that use hydrogels as binders. The presence of polycaprolactone preserved the printability of the ink and was compatible with the hydrolysis-based hardening process, despite the absence of water in the ink and its hydrophobicity. The microstructure evolved from a continuous polymeric phase with loose ceramic particles to a continuous network of hydroxyapatite nanocrystals intertwined with the polymer, in a configuration radically different from the polymer/ceramic composites obtained by fused deposition modelling. This resulted in the evolution from a ductile behavior, dominated by the polymer, to a stiffer behavior as the ceramic phase reacted. The polycaprolactone binder provides two highly relevant benefits compared to hydrogel-based inks. First, the handleability and elasticity of the as-printed scaffolds, together with the proven possibility of eliminating the solvent, opens the door to implanting the scaffolds freshly printed once lyophilized, while in a ductile state, and the hardening process to take place inside the body, as in the case of calcium phosphate cements. Second, even with a hydroxyapatite content of more than 92%, the flexural strength and toughness of the scaffolds after hardening are twice and five times those of the all-ceramic scaffolds obtained with the hydrogel-based inks, respectively., Peer Reviewed, Postprint (published version)

En aquest estudi, es van utilitzar scaffolds d'hidroxiapatita deficient en calci (CDHA) dopada amb ions, produïdes mitjançant impressió 3D, per a la regeneració òssia. La investigació pretenia caracteritzar mostres de cinc grups diferents: Control, Sr-BM, Sr-Ink, Cu-BM i Ga-BM, després de la implantació in vivo en conills en dos moments, 4 setmanes i 12 setmanes. L'objectiu principal era establir un mètode de quantificació robust per a la regeneració òssia i, posteriorment, obtenir resultats de bastides implantades en defectes del còndil femoral (en ambdós moments) i llocs intramusculars (només a les 12 setmanes). La quantificació es va aconseguir mitjançant el programari Python i Dragonfly per a volums 3D, complementat amb anàlisi histològica amb QuPath per a rodanxes 2D. Els resultats van indicar un rendiment superior de Sr-Ink, mentre que Control, Ga-BM i Sr-BM van mostrar resultats comparables, afavorint marginalment els dos últims. En particular, Cu-BM no va mostrar evidència de regeneració òssia. L'anàlisi ICP de la incorporació i alliberament d'ions va revelar l'alliberament excepcional de calci (Ca) i estronci (Sr) de Sr-Ink. Ga, tot i que present en quantitats més baixes, va demostrar un potencial regeneratiu significatiu, especialment en una mostra intramuscular. De fet, l'anàlisi SEM va mostrar la regeneració òssia mitjançant l'osteoinducció en Sr-Ink (2 mostres) i Ga-BM (1 mostra), sense cap observació en altres grups. Sr-Ink va superar constantment altres grups, possiblement atribuït al seu mètode únic d'incorporació en fase sòlida, donant lloc a un augment de la porositat. Aquest mètode distintiu probablement va facilitar l'alliberament d'ions millorat, augmentant així la regeneració òssia. Per contra, el Cu-BM pot haver patit un contingut excessiu de coure, que podria conduir a la citotoxicitat. En conclusió, aquesta caracterització exhaustiva de les bastides CDHA dopades amb ions destaca el rendiment excepcional de Sr-Ink en diversos paràmetres. Tamb, En este estudio se emplearon scaffolds de hidroxiapatita deficiente en calcio (CDHA) dopada con iones, producidos mediante impresión 3D, para la regeneración ósea. El objetivo de la investigación era caracterizar muestras de cinco grupos distintos: Control, Sr-BM, Sr-Ink, Cu-BM y Ga-BM, tras su implantación in vivo en conejos en dos momentos, 4 semanas y 12 semanas. El objetivo primario era establecer un método de cuantificación robusto para la regeneración ósea y posteriormente obtener resultados de los andamios implantados en defectos del cóndilo femoral (en ambos puntos temporales) y en sitios intramusculares (sólo a las 12 semanas). La cuantificación se logró utilizando el software Python y Dragonfly para los volúmenes 3D, complementado por el análisis histológico con QuPath para los cortes 2D. Los resultados indicaron un rendimiento superior de Sr-Ink, mientras que Control, Ga-BM y Sr-BM mostraron resultados comparables, favoreciendo marginalmente a los dos últimos. Cabe destacar que Cu-BM no mostró indicios de regeneración ósea. El análisis ICP de la incorporación y liberación de iones reveló la excepcional liberación de calcio (Ca) y estroncio (Sr) por parte de la Sr-Ink. El Ga, aunque presente en menores cantidades, demostró un potencial regenerativo significativo, especialmente en una muestra intramuscular. De hecho, el análisis SEM mostró regeneración ósea mediante osteoinducción en Sr-Ink (2 muestras) y Ga-BM (1 muestra), sin que se observara ninguna en otros grupos. Sr-Ink superó sistemáticamente a los demás grupos, posiblemente debido a su exclusivo método de incorporación en fase sólida, que dio lugar a una mayor porosidad. Este método distintivo probablemente facilitó una mayor liberación de iones, impulsando así la regeneración ósea. Por el contrario, el Cu-BM puede haber sufrido un contenido excesivo de cobre, lo que podría haber provocado citotoxicidad. En conclusión, esta exhaustiva caracterización de los andamiajes CDHA dopados con iones pone de, In this study, ion-doped calcium deficient hydroxyapatite (CDHA) scaffolds, produced via 3D printing, were employed for bone regeneration. The research aimed to characterize samples from five distinct groups: Control, Sr-BM, Sr-Ink, Cu-BM, and Ga-BM, following in vivo implantation in rabbits at two time points, 4 weeks and 12 weeks. The primary objective was to establish a robust quantification method for bone regeneration and subsequently obtain results from scaffold implanted in femoral condyle defects (at both time points) and intramuscular sites (only at 12 weeks). Quantification was achieved using Python and Dragonfly software for 3D volumes, complemented by histological analysis with QuPath for 2D slices. Results indicated superior performance from Sr-Ink, while Control, Ga-BM, and Sr-BM exhibited comparable outcomes, marginally favouring the latter two. Notably, Cu-BM did not show evidence of bone regeneration. ICP analysis of ion incorporation and release revealed Sr-Ink's exceptional release of calcium (Ca) and strontium (Sr). Ga, although present in lower quantities, demonstrated significant regenerative potential, particularly in one intramuscular sample. In fact, SEM analysis displayed bone regeneration through osteoinduction in Sr-Ink (2 samples) and Ga-BM (1 sample), with none observed in other groups. Sr-Ink consistently outperformed other groups, possibly attributed to its unique solid-phase incorporation method, resulting in increased porosity. This distinctive method likely facilitated enhanced ion release, thereby boosting bone regeneration. Conversely, Cu-BM may have suffered from excessive copper content, potentially leading to cytotoxicity. In conclusion, this comprehensive characterization of ion-doped CDHA scaffolds highlights Sr-Ink's outstanding performance across various parameters. It also holds potential for the effectiveness of incorporating Ga into scaffolds, given that even a minimal quantity demonstrated significant impact., Incoming

Human bone is a composite material composed of a mineral and organic phase. It is a living tissue that, when damaged, regenerates spontaneously and naturally to allow reconstruction or replacement of lost or damaged bone tissue. In cases of critical-sized bone defects in the maxillofacial region, spontaneous regeneration becomes impossible, necessitating guided bone regeneration (GBR) to reconstruct the defect surrounding dental implants. This surgical procedure involves the use of a bone graft and a barrier membrane to create a suitable environment for new bone cell formation. Despite this widely used process, commercially available GBR membranes exhibit numerous disadvantages and fail to be active in the bone regeneration process. This research project aims to develop an innovative GBR membrane utilizing hydroxyapatite doped with therapeutic ions to enhance its bioactivity. The production of this membrane involves the synthesis of hydroxyapatite ultra-long nanofibres doped with therapeutic ions in order to obtain a flexible and bioactive GBR membrane. The primary focus of the project is to establish a synthesis mechanism for doping hydroxyapatite ultralong nanofibres with strontium, zinc and magnesium. Two distinct mechanisms were employed, both derived from the synthesis of hydroxyapatite ultra-long nanofibres through a hydrothermal treatment of a calcium oleate precursor. The parameters studied during this project encompassed the synthesis time, the content of doping ions and the type of therapeutic ions. The first mechanism, the one-step synthesis, involves mixing all reagents to form a calcium oleate precursor with therapeutic ions, followed by high-temperature and high-pressure hydrothermal treatment. This process successfully yielded Sr-doped hydroxyapatite ultra-long nanofibres. However, further studies are required to assess the extent of doping of the fibres with magnesium and zinc as the introduction of the doping ion into the hydroxyapatite crystal latt, El hueso humano es un material constituido por una fase mineral y otra orgánica. Es un tejido vivo que, cuando se daña, se regenera de forma espontánea y natural para permitir la reconstrucción o sustitución del tejido óseo perdido o dañado. En casos de defectos óseos de tamaño crítico en la región maxilofacial, la regeneración espontánea resulta imposible, por lo que es necesaria la regeneración ósea guiada para reconstruir el defecto que rodea a los implantes dentales. Este procedimiento quirúrgico implica el uso de un injerto óseo y una membrana de barrera para crear un entorno adecuado para la formación de nuevas células óseas. A pesar de tratarse de un proceso ampliamente utilizado, las membranas GBR disponibles en el mercado presentan numerosos inconvenientes y no consiguen ser activas en el proceso de regeneración ósea. Este proyecto de investigación pretende desarrollar una membrana GBR innovadora que utilice hidroxiapatita dopada con iones terapéuticos para mejorar su bioactividad. La producción de esta membrana implica la síntesis de nanofibras ultralargas de hidroxiapatita dopadas con iones terapéuticos para obtener una membrana GBR flexible y bioactiva. El objetivo principal del proyecto es establecer un mecanismo de síntesis para dopar nanofibras ultralargas de hidroxiapatita con estroncio, zinc y magnesio. Se emplearon dos mecanismos distintos, ambos derivados de la síntesis de nanofibras ultralargas de hidroxiapatita mediante un tratamiento hidrotérmico de un precursor de oleato de calcio. Los parámetros estudiados durante este proyecto involucraron el tiempo de síntesis, el contenido de iones dopantes y el tipo de iones terapéuticos. El primer mecanismo, la síntesis en un solo paso, consiste en mezclar todos los reactivos para formar un precursor de oleato de calcio con iones terapéuticos, seguido de un tratamiento hidrotérmico a alta temperatura y alta presión. Este proceso produjo con éxito nanofibras ultralargas de hidroxiapatita dopada con Sr. Si, L'os humain est un matériau composite composé d'une phase minérale et organique. C'est un tissu vivant qui, lorsqu'il est endommagé, se régénère spontanément et naturellement pour permettre la reconstruction ou le remplacement du tissu osseux perdu ou endommagé. Dans les cas de défauts osseux de taille critique dans la région maxillo-faciale, la régénération spontanée devient impossible, ce qui nécessite une régénération osseuse guidée pour reconstruire le défaut afin de pouvoir visser un implant dentaire. Cette procédure chirurgicale implique l'utilisation d'un greffon osseux et d'une membrane barrière afin de créer un environnement propice à la formation de nouvelles cellules osseuses. Malgré ce processus de régénération osseuse guidée, les membranes actuellement disponibles dans le commerce pour la régénération osseuse guidée présentent de nombreux inconvénients et ne parviennent pas à être actives dans le processus de régénération osseuse. Ce projet de recherche vise ainsi à développer une membrane GBR innovante utilisant de l'hydroxyapatite dopée avec des ions thérapeutiques pour améliorer sa bioactivité. Ainsi, la fabrication de cette membrane implique la synthèse de nanofibres d’hydroxyapatite ultra-longues dopées avec des ions thérapeutiques afin d’obtenir une membrane flexible et bioactive. L'objectif principal du projet est d'établir un mécanisme de synthèse pour le dopage des nanofibres ultra-longues d'hydroxyapatite avec du strontium, du zinc et du magnésium. Deux mécanismes distincts ont été utilisés, tous deux dérivés de la synthèse de nanofibres ultra-longues d'hydroxyapatite par traitement hydrothermique d'un précurseur d'oléate de calcium. Les paramètres étudiés au cours de ce projet comprennent le temps de synthèse, la teneur en ions dopants et le type d'ions thérapeutiques. Le premier mécanisme, correspondant à une synthèse en une étape, implique le mélange de tous les réactifs pour former un précurseur d'oléate de calcium avec des ions thérapeuti, Incoming

Hydroxyapatite (HA) and bioglass (BG) ceramics have become of prime importance in bone tissue engineering. Besides the appropriate composition, the microstructure of bone replacement plays a crucial role. In the present work, particle composites and functionally graded material (FGM) based on HA and BG prepared by electrophoretic deposition were thoroughly characterised in terms of the preparation method, sintering process, phase composition and microstructure. The sintering was monitored by high-temperature dilatometry in two directions, the sintering rates were calculated, and the overall sintering process was discussed. The SEM showed the continuous change in the microstructure of FGM with gradual interconnected porosity favourable for bio-applications. The fundamental fractographic analysis proved the crack development in FGM related to the sintering process, and the recommendations for the reduction of the crack development were given. The phase transformations during thermal treatment were analysed using X-ray diffraction analysis and deeply discussed.

Limited bone bank capacity and risk of infection are some of the main drawbacks of autologous and allogenic grafts, giving rise to synthetic materials for bone tissue implants. The aim of this study was to process and evaluate the mechanical properties and bioactivity of magnesium and strontium doped hydroxyapatite (HAp) scaffolds and investigate the effect of adding zirconium oxide and gelatine coating the scaffolds. Doped nanosized hydroxyapatite powder was synthesized by the hydrothermal method and the scaffolds were made by the foam replica technique and sintered at different temperatures. Yttria-stabilized zirconium oxide (YSZ), synthesized by plasma technology, was used as reinforcement of calcium phosphate scaffolds. Element analysis, phase composition, morphology of the powders and microstructure of the scaffolds were investigated, as well as the compressive strength of the coated and uncoated scaffolds and bioactivity in simulated body fluid (SBF). A microporous structure was achieved with interconnected pores and bioactivity in SBF was confirmed in all cases. The best mechanical properties were given by the coated composite HAp/YSZ scaffolds, withstanding average stresses of over 1019 kPa. These results encourage the idea of use of these scaffolds in bone regenerative therapy and bone tissue engineering.

Vat photopolymerization is an additive manufacturing technique that utilizes photosensitive resins to fabricate 3D polymeric objects with high precision. However, these objects often lack mechanical strength. This study investigated the strengthening of a resin based on epoxidized soybean oil acrylate, specifically designed for vat photopolymerization, by the in situ formation of hydroxyapatite nanocrystals. First, a stable alpha tricalcium phosphate (-TCP)-resin feedstock mixture was developed (~30 vol.% -TCP), which proved suitable for fabricating monoliths as well as complex triply periodic minimal surface (gyroid, diamond, and Schwarz) porous structures through vat photopolymerization. The results demonstrated that the incorporation of -TCP particles led to a significant mechanical improvement of the resin. Second, post-printing hydrothermal treatments were utilized to transform the -TCP particles into hydroxyapatite crystals within the resin. It was observed that the space between hydroxyapatite crystals within the composites was occupied by the cured resin, resulting in a more compact, stronger, and mechanically more reliable material than the porous hydroxyapatite produced by the hydrolysis of -TCP mixed with water. Moreover, water absorption during the hydrothermal treatments caused the plasticization of the cured resin. As a consequence, the hydroxyapatite-resin composites displayed slightly lower mechanical properties compared to the as-printed -TCP-resin composite.

L'os és un òrgan amb una alta capacitat de regeneració, aquesta regeneració ve donada per l'activitat coordinada de les cèl·lules òssies, però quan el defecte generat és molt gran o les cèl·lules tenen alguna patologia és necessari usar un implant que les cèl·lules puguin utilitzar com a suport on moure's i crear el nou teixit. Entre tots els tipus d'implants que hi ha disponibles el que presenta menys problemes és l'ús d'un material sintètic, això ha fet que l'ús de biomaterials sintètics capaços d'imitar la matriu extracel·lular dels ossos es vegi potenciat, un exemple és la hidroxiapatita. En aquest Treball de fi de màster (TFM), l'objectiu principal és aconseguir formar implants ossis a partir de les nanofibras de hidroxiapatita, ja que amb aquesta morfologia s'aconsegueix un material ceràmic amb unes propietats elàstiques mai vistes. Aquestes nanofibras s'han sintetitzat mitjançant un procés hidrotèrmic amb l'ajuda d'una molècula orgànica, en aquest cas oleat sòdic, que ajuda a direccionar el creixement del material. Durant aquest treball de fi de màster s'estudiaran diversos paràmetres principals en la síntesi de les nanofibras; el temps de síntesi, l'efecte de la pressió i la concentració dels components. Per a observar les diferències entre síntesis, les fibres seran observades en el TEM i el SEM. També seran analitzades amb FTIR, DSC i DRX per a veure la composició de les fibres i es calculés la superfície especifica mitjançant la tècnica ASAP. A més, també s'establirà un valor per a comparar el rendiment de cada síntesi. També s'ha avaluat la capacitat de consolidar les fibres en bastides tridimensionals. Per a això s'estudiaran dues vies “Ice templating” i impressió 3d per extrusió., El hueso es un órgano con una alta capacidad de regeneración, esta regeneración viene dada por la actividad coordinada de las células óseas, pero cuando el defecto generado es muy grande o las células tienen alguna patología es necesario usar un implante que las células puedan utilizar como soporte donde moverse y crear el nuevo tejido. Entre todos los tipos de implantes que hay disponibles el que presenta menos problemas es el uso de un material sintético, esto ha hecho que el uso de biomateriales sintéticos capaces de imitar la matriz extracelular de los huesos se vea potenciado, un ejemplo es la hidroxiapatita. En este Trabajo de fin de máster (TFM), el objetivo principal es conseguir formar implantes óseos a partir de las nanofibras de hidroxiapatita, ya que con esta morfología se consigue un material cerámico con unas propiedades elásticas nunca vistas. Estas nanofibras se han sintetizado mediante un proceso hidrotérmico con la ayuda de una molécula orgánica, en este caso oleato sódico, que ayuda a direccionar el crecimiento del material. Durante este trabajo de fin de máster se estudiarán varios parámetros principales en la síntesis de las nanofibras; el tiempo de síntesis, el efecto de la presión y la concentración de los compuestos. Para observar las diferencias entre síntesis, las fibras serán observadas en el TEM y el SEM. También serán analizadas con FTIR, DSC y DRX para ver la composición de las fibras y se calculara la superficie especifica mediante la técnica ASAP. Además, también se establecerá un valor para comparar el rendimiento de cada síntesis. También se ha evaluado la capacidad de consolidar las fibras en andamios tridimensionales. Para ello se estudiarán dos vías “Ice templating” y impresión 3d por extrusión., Bone is an organ with a high capacity for regeneration, this regeneration is given by the coordinated activity of bone cells, but when the defect generated is very large or the cells have some pathology, it is necessary to use an implant that the cells can use as a support where they can move and create new tissue. Among all the types of implants available, the one that presents the fewest problems is the use of a synthetic material. This has led to the use of synthetic biomaterials capable of imitating the extracellular matrix of bones, one example being hydroxyapatite. In this Master's thesis (TFM), the main objective is to form bone implants from hydroxyapatite nanofibres, as this morphology results in a ceramic material with unprecedented elastic properties. These nanofibres have been synthesised by means of a hydrothermal process with the help of an organic molecule, in this case sodium oleate, which helps to direct the growth of the material. During this master's thesis, several main parameters in the synthesis of nanofibres will be studied; the synthesis time, the effect of pressure and the concentration of the reagents. To observe the differences between syntheses, the fibres will be observed in TEM and SEM. They will also be analysed by FTIR, DSC and XRD to see the composition of the fibres and the specific surface area will be calculated using the ASAP technique. In addition, a value will also be established to compare the performance of each synthesis. The ability to consolidate the fibres into three-dimensional scaffolds has also been evaluated. For this purpose, two routes will be studied: Ice templating and 3D printing by extrusion.

Raman spectroscopy is widely used to examine the carbonate content within bone apatite, but Raman spectra are also sensitive to orientation effects between the polarisation of the incoming laser light and the sample orientation. This may lead to discrepancies when using Raman spectroscopy to evaluate the carbonate content as the extent of crystal organisation can change depending on the type of bone, age, and presence of mineralisation disorders in the organism. It is experimentally very challenging to evaluate the effect of orientation using individual bone crystals. Therefore, we have used density functional theory to examine the effect of orientation in apatitic materials. We examined hydroxyapatite and three different types of carbonated apatite: A-type where the carbonate ion substitutes the two OH groups in the unit cell, B-type where co-substitution occurs between carbonate in a phosphate position and Na+ for Ca2+ to maintain charge balance, and AB-type where carbonate sits in both A-site and B-site. Our simulations show that the OH group in hydroxyapatite has a strong orientation dependence, consistent with previous literature. In addition, the phosphate and carbonate bands of the apatitic structures are predicted to be orientation dependent, where the maximum scattering efficiency occurs in configurations in which the laser polarisation is parallel to the crystallographic axes of the material. The intensity changes of the phosphate and carbonate bands are not consistent upon changing orientations and thus may lead to an underestimation of carbonate contents if insufficient sampling points are used during bone analysis.

The two component micro-powder injection molding (2C-?PIM) process has evolved from ?PIM process because of the increasing demand for multi-functional micro-components applications. In this research work, the selected materials to fabricate micro-sized bi-material parts are zirconia (ZrO2) and hydroxyapatite (HA). ZrO2 is chosen for structural integrity and bio-inert, while HA is mainly chosen for bio-active properties. The reason of employing the multi-component binders is to ensure the flowability of the feedstock. Feedstock rheological characteristics needs to be carefully investigated to avoid any undesirable and inhomogeneous mixture between powder and binder. A common binder system which is comprised of palm stearin and low-density polyethylene (LDPE) were mixed with individual ZrO2 and HA powder particles to prepare for ZrO2 and HA feedstocks. Typically, the feedstocks were obtained ZrO2 and HA powders independently with a binder ratio of 60 wt.% of palm stearin and 40wt.% low-density polyethylene (LDPE). The mixing was carried out in Brabender mixer. Before mixing, critical powder volume percentage (CPVP) analysis was carried out to determine the optimal powder loadings required to prepare the ZrO2 and HA feedstocks. In this research work, the obtained CPVP of ZrO2 and HA powders were 47.0 and 59.0 vol.%, respectively. Based on CPVP analysis, six feedstocks with optimal powder loadings of 43, 44 and 45 vol.% for ZrO2 and 54, 55 and 56 vol.% for HA were prepared. The rheological analysis involving viscosity, shear rate, flow behavior index, activation energy and moldability index was investigated using capillary rheometer. Based on the obtained rheology result, it shows that the overall shear rate and viscosity are within the 2C-?PIM process recommended range. All tested composition shows pseudoplastic behavior. The results of the study found that ZrO2 and HA with optimal powder loadings of 55 vol.% and 44 vol.% have good rheological properties compared to fe

Calcium phosphates are widely present in geological and industrial settings and make up the majority of our bone’s inorganic content; however, their formation from solution is not fully understood. The nucleation of calcium phosphate phases was studied using a state-of-the-art titration setup. The effect of varied calcium addition rate was studied at a range of pH values between pH 7 and pH 8; the precipitated crystals were isolated and analyzed. Dicalcium phosphate dihydrate (DCPD) was formed at lower pH and a slow addition rate. Intermediate addition rates yielded a mix of DCPD and poorly crystalline hydroxyapatite (PC-HA). At fast addition rates and above pH 7.5, poorly crystalline hydroxyapatite was precipitated exclusively. The results indicate that counterintuitive kinetic effects play a substantial role in the nucleation of calcium phosphates.

[Abstract]: Sixteenth-century mural paintings of Nossa Senhora das Neves in Vilar de Perdizes (Galicia—North Portugal Euroregion) were analysed. An iconographic study has allowed us to understand the meaning of the seven scenes that constitute the mural painting. X-ray fluorescence (XRF) and Raman spectroscopies determined the compounds used in this mural painting, both in the original and in later repaintings. The black paint was bone black. Hydroxyapatite characteristic bands and those of the associated phosphates have been identified. White lime was used as white paint. Lepidocrocite and goethite were used to make yellows, and hematite was used to make red shades. Cinnabar has been used for a later red repaint. Carbon-based compounds and rutile were used to create different tonalities by darkening or lightening colours. It is of great significance to obtain accurate and reliable mural painting information through scientific means, since preservation, restoration, and repainting without detailed information can be harmful to mural paintings.

Lately, there has been an increasing demand for materials that could improve tissue regenerative therapies and provide antimicrobial effects. Similarly, there is a growing need to develop or modify biomaterials for the diagnosis and treatment of different pathologies. In this scenario, hydroxyapatite (HAp) appears as a bioceramic with extended functionalities. Nevertheless, there are certain disadvantages related to the mechanical properties and lack of antimicrobial capacity. To circumvent them, the doping of HAp with a variety of cationic ions is emerging as a good alterative due to the different biological roles of each ion. Among many elements, lanthanides are understudied despite their great potential in the biomedical field. For this reason, the present review focuses on the biological benefits of lanthanides and how their incorporation into HAp can alter its morphology and physical properties. A comprehensive section of the applications of lanthanides-substituted HAp nanoparticles (HAp NPs) is presented to unveil the potential biomedical uses of these systems. Finally, the need to study the tolerable and non-toxic percentages of substitution with these elements is highlighted., Peer Reviewed, Postprint (published version)

Despite increased orthopedic biomaterial research activity over previous decades, relatively few novel biomaterials have made it to clinical use. This may partially be due to the inability of existing in vitro testing routines to sufficiently replicate the physiological environment, leading to potentially inaccurate assessments of a biomaterial’s therapeutic potential. To address this, mathematical modelling and microfluidic design principles were assessed as possible supportive strategies to better improve the informativity of in vitro testing approaches. Using principles of the Langmuir isotherm, a predictive computational model was constructed to capture the dynamics of protein and cell adhesion on a biomaterial surface, specifically on calcium-deficient hydroxyapatite, which is a synthetic biomaterial that is compositionally similar to the inorganic phase of the bone. The results demonstrated the success of the model at capturing the trends of the data, thereby indicating potential use as a predicative tool to assist with in vitro data interpretation. Furthermore, attempts were made to improve the in vitro environment towards better physiological relevancy via the introduction of microfluidics, which is method of precise fluid control in micron-sized channels. For instance, the use of microfluidics allows for cell culture under more tissue relevant length scales, as well as the provision of a continuous media flow, which facilitates nutrient delivery and activation of mechanosensitive pathways through shear stress. Through development of such “Biomaterial-on-chip” microfluidic platforms, a general increase in cell viability and proliferation was seen when cells were cultured under flow. The effect of flow on other parameters such as material-induced ionic exchange, immunogenicity and mechanotransduction was also tested using the platform. By the culmination of the thesis work, the Biomaterial-on-chip platform was designed with inherent standardization, allowing