A new calcium releasing nano-composite biomaterial for bone tissue engineering scaffolds

A biomaterial with bioactive glass nanoparticles (nBG) and Ca2+ incorporated into alginate matrix was developed. Films characterization was carried out by SEM, IR, tensile strength measurements, bioactivity assay, degradation and swelling studies. Ca2+ release from films was analyzed. Freeze-dried-scaffolds were also fabricated. Films showed the development of a homogeneous matrix and the mechanical properties were improved when nBG were incorporated. The bioactive nature of nBG containing films was confirmed by studies in simulated body fluid. Degradation was negligible and a good swelling capacity was observed. Moreover Ca2+ was released in a controlled manner. In scaffolds fabricated by freeze-drying, pores were seen to be uniform and well distributed. According to the characterization results, these composite biomaterials are attractive candidates for the fabrication of bone tissue engineering scaffolds.Fil: Cattalini, Juan Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Garcia, J,. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Boccaccini, A. R.. Universitat Erlangen-Nuremberg; Alemania;Fil: Lucangioli, Silvia Edith. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Mouriño, Viviana Silvia Lourdes. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Novel nanocomposite biomaterials with controlled copper/calcium release capability for bone tissue engineering multifunctional scaffolds

This work aimed to develop novel composite biomaterials for bone tissue engineering (BTE) made of bioactive glass nanoparticles (Nbg) and alginate cross-linked with Cu2+ or Ca2+ (AlgNbgCu, AlgNbgCa, respectively). Twodimensional scaffolds were prepared and the nanocomposite biomaterials were characterized in terms of morphology, mechanical strength, bioactivity, biodegradability, swelling capacity, release profile of the cross-linking cations and angiogenic properties. It was found that both Cu2+ and Ca2+ are released in a controlled and sustained manner with no burst release observed. Finally, in vitro results indicated that the bioactive ions released from both nanocomposite biomaterials were able to stimulate the differentiation of rat bone marrow-derived mesenchymal stem cells towards the osteogenic lineage. In addition, the typical endothelial cell property of forming tubes in Matrigel was observed for human umbilical vein endothelial cells when in contact with the novel biomaterials, particularly AlgNbgCu, which indicates their angiogenic properties. Hence, novel nanocomposite biomaterials made of Nbg and alginate cross-linked with Cu2+ or Ca2+ were developed with potential applications for preparation of multifunctional scaffolds for BTE.Fil: Cattalini, Juan Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Hoppe, A.. Universitat Erlangen-Nuremberg; AlemaniaFil: Pishbin, F.. Imperial College London; Reino UnidoFil: Roether, Judith A.. Universitat Erlangen-Nuremberg; AlemaniaFil: Boccaccini, Aldo R.. Universitat Erlangen-Nuremberg; AlemaniaFil: Lucangioli, Silvia Edith. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mouriño, Viviana Silvia Lourdes. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Metallic ions as therapeutic agents in tissue engineering scaffolds: an overview of their biological applications and strategies for new developments

This article provides an overview on the application of metallic ions in the fields of regenerative medicine and tissue engineering, focusing on their therapeutic applications and the need to design strategies for controlling the release of loaded ions from biomaterial scaffolds. A detailed summary of relevant metallic ions with potential use in tissue engineering approaches is presented. Remaining challenges in the field and directions for future research efforts with focus on the key variables needed to be taken into account when considering the controlled release of metallic ions in tissue engineering therapeutics are also highlighted

Desarrollo de biomateriales innovadores aplicables al diseño de andamios destinados a ingeniería tisular ósea

The aim of this thesis was to develop novel composite biomaterials made of alginate and bioactive glass nanoparticles to develop tridimensional scaffolds able to release therapeutic agents as Cu2+, Ca2+ and alendronate, to be considered for bone tissue engineering applications. Matrices in two dimensions were prepared and used in a preliminary study about the biomaterial properties, which allowed us to assay the viability of using these biomaterials in the elaboration of tridimensional and multifunctional scaffolds for bone tissue engineering. Then, it was demonstrated that the scaffolds developed had interesting properties in terms of morphology, porosity, mechanical strength, bioactivity, biodegradability and citocompatibility. In addition, it is important to note that the scaffolds showed suitable release profile of Cu2+ or Ca2+ ions, and alendronate, for promoting the proliferation of bone and endothelial cells, as well as the formation of blood vessels in an in vivo model. Furthermore, this thesis proposed the development and validation of novel and simple analytical techniques based on capillary electrophoresis to quantify the release of the therapeutic agents incorporated. These methods resulted versatile, economical and efficient for the quantification of the agents mentioned above, which were released in concentrations on the order of parts of million.Fil: Cattalini, Juan Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaEl presente trabajo de tesis propuso el desarrollo de un novedoso biomaterial compuesto, elaborado a partir de alginato y nanopartículas de biovidrio, con potencial aplicación en la ingeniería tisular ósea para el desarrollo de andamios tridimensionales multifuncionales con capacidad de liberar agentes terapéuticos como iones Cu2+ o Ca2+, y un bisfosfonato como el alendronato. El estudio preliminar del desarrollo de los biomateriales, sobre matrices en dos dimensiones, permitió evaluar la viabilidad de su aplicación en la elaboración de andamios tridimensionales. Luego, se demostró que los andamios desarrollados poseen propiedades interesantes en términos de morfología, porosidad, resistencia mecánica, bioactividad, biodegradabilidad y citocompatibilidad. Asimismo, es importante destacar que los andamios mostraron un perfil de liberación de Cu2+, Ca2+ y alendronato, adecuado para favorecer la proliferación de células óseas y endoteliales, así como la formación de vasos sanguíneos en un modelo considerado in vivo. Además, el trabajo de tesis planteó, por primera vez, el desarrollo y la validación de técnicas analíticas basadas en la electroforesis capilar para la cuantificación de los mencionados agentes liberados desde las matrices elaboradas. Dichos métodos resultaron simples, versátiles, económicos y eficientes, teniendo en cuenta que dichos agentes terapéuticos son liberados desde las matrices en concentraciones del orden de las partes por millón

Development and validation of a novel sensitive UV-direct capillary electrophoresis method for quantification of alendronate in release studies from biomaterials

A simple, highly sensitive, and robust CE method applied to the determination of alendronate (ALN) was developed from matrices for tissue engineering, characterized by being highly complex systems. The novel method was based on the ALN derivatization with o-phthalaldehyde and 2-mercaptoethanol for direct ultraviolet detection at 254 nm. The BGE consisted of 20 mM sodium borate buffer at pH 10, and the electrophoretic parameters were optimized.The method was validated in terms of specificity, linearity, LOD, LOQ, precision, accuracy, and robustness. The LOD and LOQ obtained were 0.8 and 2.7 μg/mL, respectively. In addition, the method offers higher sensitivity and specificity compared to other CE and HPLC methods using UV-detectors, as well as low cost and simplicity that allowed the rapid and simple quantitation of ALN from bone regeneration matrices.Fil: Cattalini, Juan Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Mouriño, Viviana Silvia Lourdes. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Lucangioli, Silvia Edith. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Determination of copper in composite biomaterials by capillary electrophoresis: an UV-direct method based on in situ complex formation

This work describes the optimization and validation of an UV-direct capillary electrophoresis method for the analysis of copper ions in samples obtained from release studies of bone-tissue-engineering composite biomaterials. Ethylenediaminetetraacetic acid was used as a complexing agent added to the background electrolyte to modulate the selectivity of the separation and quantitation of free copper ions. The separations were performed under reverse polarity and the parameters of validation such as specificity, linearity, limits of detection and quantitation, precision, accuracy and robustness were evaluated. The method resulted to be suitable for copper determination in biomaterials and showed advantages such as rapidness, specificity and suitable sensibility, achieving a limit of detection and quantitation of 0.05 and 0.16 μg mL−1, respectively.Fil: Cattalini, Juan Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Mouriño, Viviana Silvia Lourdes. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Lucangioli, Silvia Edith. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Development and validation of a Capillary Zone Electrophoresis method for the determination of calcium in composite biomaterials

This work presents the development and validation of a capillary zone electrophoresis method for calcium ions release quantitation from composite biomaterials with potential application in bone tissue engineering. Calcium ions quantitation was made using a fused silica capillary (40 cm, 75 µm ID) and background electrolyte containing 5 mM imidazole, 6 mM á-hydroxyisobutyric acid, 1 mM 1,4,7,10,13,16-hexaoxacyclo-octadecane and 20 % w/v methanol, at pH 4.5. Indirect UV-detection mode at 214 nm was performed. The separations were achieved using normal polarity at 6 kV, a cartridge temperature of 25 µC and 0.5 psi for 5 s for sample introduction. Parameters of validation such as specificity, linearity, limit of detection and quantitation, accuracy, precision and robustness were evaluated according to the International Conference on Harmonization guidelines. The new developed method resulted to be suitable for calcium determination from composite biomaterials for potential application in bone tissue engineering.Fil: Cattalini, Juan Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: García, Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina;Fil: Mouriño, Viviana Silvia Lourdes. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Lucangioli, Silvia Edith. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina

Bisphosphonate-Based Strategies for Bone Tissue Engineering and Orthopedic Implants

Bisphosphonates (BPs) are a group of well-established drugs applied in the development of metabolic bone disorder-related therapies. There is increasing interest also in the application of BPs in the context of bone tissue engineering which is the topic of this review in which an extensive overview of published studies on the development and applications of BPs based strategies for bone regeneration is provided with special focus on the rationale for the use of different BPs in three dimensional (3D) bone tissue scaffolds. Different alternatives investigated to address the delivery and sustained release of these therapeutic drugs in the nearby tissues are discussed comprehensively and the most significant published approaches on bisphosphonate-conjugated drugs in multifunctional 3D scaffolds as well as the role of bisphosphonates within coatings for improved fixation of orthopaedic implants are presented and critically evaluated. Finally, the authors’ views regarding the remaining challenges in the fields and directions for future research efforts are highlighted.Fil: Cattalini, Juan Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Boccaccini, Aldo R.. Universitat Erlangen-Nuremberg; AlemaniaFil: Lucangioli, Silvia Edith. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Mouriño, Viviana Silvia Lourdes. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Multifunctional scaffolds for bone tissue engineering and in situ drug delivery

This chapter provides an overview about the development of bone tissue engineering scaffolds with capability for the controlled delivery of therapeutic drugs. Typical drugs considered include gentamicin and other antibiotics generally used to combat osteomyelitis as well as anti-inflammatory drugs and bisphosphonates. Special attention has been given to the technology used for controlling the release of the loaded drugs. A detailed summary of drugs included in bone tissue scaffolds is presented and the several approaches developed to combine organic and inorganic biomaterials in composites for drug delivery systems are discussed. The remaining challenges in the field are summarized suggesting also future research directions.Fil: Mouriño, Viviana Silvia Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Cattalini, Juan Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Wei, L.. No especifíca;Fil: Boccaccini, A. R.. No especifíca;Fil: Lucangioli, Silvia Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentin