Juan Pablo Cattalini

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.

Composite polymer-bioceramic scaffolds with drug delivery capability for bone tissue engineering

Introduction: Next-generation scaffolds for bone tissue engineering (BTE) should exhibit the appropriate combination of mechanical support and morphological guidance for cell proliferation and attachment while at the same time serving as matrices for sustained delivery of therapeutic drugs and/or biomolecular signals, such as growth factors. Drug delivery from BTE scaffolds to induce the formation of functional tissues, which may need to vary temporally and spatially, represents a versatile approach to manipulating the local environment for directing cell function and/or to treat common bone diseases or local infection. In addition, drug delivery from BTE is proposed to either increase the expression of tissue inductive factors or to block the expression of others factors that could inhibit bone tissue formation. Composite scaffolds which combine biopolymers and bioactive ceramics in mechanically competent 3D structures, including also organic–inorganic hybrids, are being widely developed for BTE, where the affinity and interaction between biomaterials and therapeutic drugs or biomolecular signals play a decisive role in controlling the release rate. Areas covered: This review covers current developments and applications of 3D composite scaffolds for BTE which exhibit the added capability of controlled delivery of therapeutic drugs or growth factors. A summary of drugs and biomolecules incorporated in composite scaffolds and approaches developed to combine biopolymers and bioceramics in composites for drug delivery systems for BTE is presented. Special attention is given to identify the main challenges and unmet needs of current designs and technologies for developing such multifunctional 3D composite scaffolds for BTE. Expert opinion: One of the major challenges for developing composite scaffolds for BTE is the incorporation of a drug delivery function of sufficient complexity to be able to induce the release patterns that may be necessary for effective osseointegration, vascularization and bone regeneration. Loading 3D scaffolds with different biomolecular agents should produce a codelivery system with different, predetermined release profiles. It is also envisaged that the number of relevant bioactive agents that can be loaded onto scaffolds will be increased, whilst the composite scaffold design should exploit synergistically the different degradation profiles of the organic and inorganic components.

Physicochemical, biological and drug-release properties of gallium crosslinked alginate/nanoparticulate bioactive glass composite films

The aim of this work was to develop biodegradable and bioactive materials with sufficient structural integrity and prophylaxis effect against infection based on alginate-bioactive glass composite. The incorporation of bioactive glass nanoparticles (NBG) into Ga-crosslinked alginate films significantly improved their mechanical properties when compared with films fabricated with micron-sized bioactive glass particles. In addition, Ga-alginate films containing NBG induced a bacteriostatic effect in vitro towards S. aureus due to the presence of Ga ions (Ga3+), whose release is controlled solely by crosslinking the ion with alginate. Biomineralization studies in simulated body fluid suggested the deposition of hydroxyapatite on the surface of the films indicating their bioactive nature. In addition, the films were shown to feature biocompatibility toward osteoblast-like cells. Thus, it was shown that Ga-crosslinked composite films possessed relevant physicochemical, biological and controlled bacteriostatic effects which make these materials promising candidates for bone tissue engineering applications.

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). Two-dimensional 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.

Nanocomposite scaffolds with tunable mechanical and degradation capabilities: co-delivery of bioactive agents for bone tissue engineering

Novel multifunctional nanocomposite scaffolds made of nanobioactive glass and alginate crosslinked with therapeutic ions such as calcium and copper were developed for delivering therapeutic agents, in a highly controlled and sustainable manner, for bone tissue engineering. Alendronate, a well-known antiresorptive agent, was formulated into microspheres under optimized conditions and effectively loaded within the novel multifunctional scaffolds with a high encapsulation percentage. The size of the cation used for the alginate crosslinking impacted directly on porosity and viscoelastic properties, and thus, on the degradation rate and the release profile of copper, calcium and alendronate. According to this, even though highly porous structures were created with suitable pore sizes for cell ingrowth and vascularization in both cases, copper-crosslinked scaffolds showed higher values of porosity, elastic modulus, degradation rate and the amount of copper and alendronate released, when compared with calcium-crosslinked scaffolds. In addition, in all cases, the scaffolds showed bioactivity and mechanical properties close to the endogenous trabecular bone tissue in terms of viscoelasticity. Furthermore, the scaffolds showed osteogenic and angiogenic properties on bone and endothelial cells, respectively, and the extracts of the biomaterials used promoted the formation of blood vessels in an ex vivo model. These new bioactive nanocomposite scaffolds represent an exciting new class of therapeutic cell delivery carrier with tunable mechanical and degradation properties; potentially useful in the controlled and sustainable delivery of therapeutic agents with active roles in bone formation and angiogenesis, as well as in the support of cell proliferation and osteogenesis for bone tissue engineering.

Multifunctional scaffolds for bone tissue engineering and in situ drug delivery

Abstract: This chapter provides an overview about the development of bone tissue engineering scaffolds with the ability to provide 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 many 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.

Development and Validation of a Capillary Zone Electrophoresis Method for the Determination of Calcium in Composite Biomaterials

Fil: Cattalini, Juan Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Tecnologia Farmaceutica; Argentina; Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay; Argentina;

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.

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.