Carlos A. García-González

Polysaccharide-based aerogel microspheres for oral drug delivery.

Polysaccharide-based aerogels in the form of microspheres were investigated as carriers of poorly water soluble drugs for oral administration. These bio-based carriers may combine the biocompatibility of polysaccharides and the enhanced drug loading capacity of dry aerogels. Aerogel microspheres from starch, pectin and alginate were loaded with ketoprofen (anti-inflammatory drug) and benzoic acid (used in the management of urea cycle disorders) via supercritical CO2-assisted adsorption. Amount of drug loaded depended on the aerogel matrix structure and composition and reached values up to 1.0×10(-3) and 1.7×10(-3) g/m(2) for ketoprofen and benzoic acid in starch microspheres. After impregnation, drugs were in the amorphous state in the aerogel microspheres. Release behavior was evaluated in different pH media (pH 1.2 and 6.8). Controlled drug release from pectin and alginate aerogel microspheres fitted Gallagher-Corrigan release model (R(2)>0.99 in both cases), with different relative contribution of erosion and diffusion mechanisms depending on the matrix composition. Release from starch aerogel microspheres was driven by dissolution, fitting the first-order kinetics due to the rigid starch aerogel structure, and showed different release rate constant (k1) depending on the drug (0.075 and 0.160 min(-1) for ketoprofen and benzoic acid, respectively). Overall, the results point out the possibilities of tuning drug loading and release by carefully choosing the polysaccharide used to prepare the aerogels.

Synthesis and biomedical applications of aerogels: Possibilities and challenges

Aerogels are an exceptional group of nanoporous materials with outstanding physicochemical properties. Due to their unique physical, chemical, and mechanical properties, aerogels are recognized as promising candidates for diverse applications including, thermal insulation, catalysis, environmental cleaning up, chemical sensors, acoustic transducers, energy storage devices, metal casting molds and water repellant coatings. Here, we have provided a comprehensive overview on the synthesis, processing and drying methods of the mostly investigated types of aerogels used in the biological and biomedical contexts, including silica aerogels, silica-polymer composites, polymeric and biopolymer aerogels. In addition, the very recent challenges on these aerogels with regard to their applicability in biomedical field as well as for personalized medicine applications are considered and explained in detail.

Processing of Materials for Regenerative Medicine Using Supercritical Fluid Technology.

The increase in the world demand of bone and cartilage replacement therapies urges the development of advanced synthetic scaffolds for regenerative purposes, not only providing mechanical support for tissue formation, but also promoting and guiding the tissue growth. Conventional manufacturing techniques have severe restrictions for designing these upgraded scaffolds, namely, regarding the use of organic solvents, shearing forces, and high operating temperatures. In this context, the use of supercritical fluid technology has emerged as an attractive solution to design solvent-free scaffolds and ingredients for scaffolds under mild processing conditions. The state-of-the-art on the technological endeavors for scaffold production using supercritical fluids is presented in this work with a critical review on the key processing parameters as well as the main advantages and limitations of each technique. A special stress is focused on the strategies suitable for the incorporation of bioactive agents (drugs, bioactive glasses, and growth factors) and the in vitro and in vivo performance of supercritical CO2-processed scaffolds.

Growth factors delivery from hybrid PCL-starch scaffolds processed using supercritical fluid technology.

Synthetic polymeric scaffolds to be used as surrogates of autologous bone grafts should not only have suitable physicochemical and mechanical properties, but also contain bioactive agents such as growth factors (GFs) to facilitate the tissue growth. For this purpose, cost-effective and autologous GFs sources are preferred to avoid some post-surgery complications after implantation, like immunogenicity or disease transmission, and the scaffolds should be processed using methods able to preserve GFs activity. In this work, poly(ɛ-caprolactone) (PCL) scaffolds incorporating GFs were processed using a green foaming process based on supercritical fluid technology. Preparation rich in growth factors (PRGF), a natural and highly available cocktail of GFs obtained from platelet rich plasma (PRP), was used as GF source. PCL:starch:PRGF (85:10:5 weight ratio) porous solid scaffolds were obtained by a supercritical CO2-assisted foaming process at 100 bar and 37 °C with no need of post-processing steps. Bioactivity of GFs after processing and scaffold cytocompatibility were confirmed using mesenchymal stem cells. The performance of starch as GF control release component was shown to be dependent on starch pre-gelification conditions.

Prilling and supercritical drying: A successful duo to produce core-shell polysaccharide aerogel beads for wound healing.

Bacterial infections often affect the wound, delaying healing and causing areas of necrosis. In this work, an aerogel in form of core-shell particles, able to prolong drug activity on wounds and to be easily removed was developed. Aerogel microcapsules consisted of a core made by amidated pectin hosting doxycycline, an antibiotic drug with a broad spectrum of action, and a shell consisting of high mannuronic content alginate. Particles were obtained by prilling using a coaxial nozzle for drop production and an ethanolic solution of CaCl2 as gelling promoter. The alcogels where dried using supercritical CO2. The influence of polysaccharides and drug concentrations on aerogel properties was evaluated. Spherical particles with high drug encapsulation efficiency (87%) correlated to alginate concentration in the processed liquid feeds were obtained. The release of the drug, mainly concentrated into the pectin core, was prolonged till 48h, and dependent on both drug/pectin ratio and alginate concentration.

Polyamide 6/chitosan nanofibers as support for the immobilization of Trametes versicolor laccase for the elimination of endocrine disrupting chemicals.

In recent years, there has been an increase in efforts to improve wastewater treatment as the concentration of dangerous pollutants, such as endocrine disrupting chemicals, in wastewater increases. These compounds, which mimic the effect of hormones, have a negative impact on human health and are not easily removed from water. One way to effectively eliminate these pollutants is to use enzymatically activated materials. In this study, we report on the use of laccase from the white rot fungus Trametes versicolor immobilized onto polyamide 6/chitosan (PA6/CHIT) nanofibers modified using two different spacers (bovine serum albumin and hexamethylenediamine). We then tested the ability of the PA6/CHIT-laccase biocatalysts to eliminate a mixture containing 50μM of two endocrine disrupting chemicals: bisphenol A and 17α-ethinylestradiol. The PA6/CHIT nanofiber matrix used in this study not only proved to be a suitable carrier for immobilized and modified laccase but was also efficient in the removal of a mixture of endocrine disrupting chemicals in three treatment cycles.

Stimuli-responsive polymers for antimicrobial therapy: drug targeting, contact-killing surfaces and competitive release

ABSTRACT Introduction: Polymers can be designed to modify their features as a function of the level and nature of the surrounding microorganisms. Such responsive polymers can endow drug delivery systems and drug-medical device combination products with improved performance against intracellular infections and biofilms. Areas covered: Knowledge on microorganism growth environment outside and inside cells and formation of biofilm communities on biological and synthetic surfaces, together with advances in materials science and drug delivery are prompting strategies with improved efficacy and safety compared to traditional systemic administration of antimicrobial agents. This review deals with antimicrobial strategies that rely on: (i) polymers that disintegrate or undergo phase-transitions in response to changes in enzymes, pH and pO2 associated to microorganism growth; (ii) stimuli-responsive polymers that expose contact-killing groups when microorganisms try to adhere; and (iii) bioinspired polymers that recognize microorganisms for triggered (competitive/affinity-driven) drug release. Expert opinion: Prophylaxis and treatment of infections may benefit from polymers that are responsive to the unique changes that microbial growth causes in the surrounding environment or that even recognize the microorganism itself or its quorum sensing signals. These polymers may offer novel tools for the design of macrophage-, bacteria- and/or biofilm-targeted nanocarriers as well as of medical devices with switchable antibiofouling properties.

Cyclodextrins as versatile building blocks for regenerative medicine

&NA; Cyclodextrins (CDs) are one of the most versatile substances produced by nature, and it is in the aqueous biological environment where the multifaceted potential of CDs can be completely unveiled. CDs form inclusion complexes with a variety of guest molecules, including polymers, producing very diverse biocompatible supramolecular structures. Additionally, CDs themselves can trigger cell differentiation to distinct lineages depending on the substituent groups and also promote salt nucleation. These features together with the affinity‐driven regulated release of therapeutic molecules, growth factors and gene vectors explain the rising interest for CDs as building blocks in regenerative medicine. Supramolecular poly(pseudo)rotaxane structures and zipper‐like assemblies exhibit outstanding viscoelastic properties, performing as syringeable implants. The sharp shear‐responsiveness of the supramolecular assemblies is opening new avenues for the design of bioinks for 3D printing and also of electrospun fibers. CDs can also be transformed into polymerizable monomers to prepare alternative nanostructured materials. The aim of this review is to analyze the role that CDs may play in regenerative medicine through the analysis of the last decade research. Most applications of CD‐based scaffolds are focussed on non‐healing bone fractures, cartilage reparation and skin recovery, but also on even more challenging demands such as neural grafts. For the sake of clarity, main sections of this review are organized according to the architecture of the CD‐based scaffolds, mainly syringeable supramolecular hydrogels, 3D printed scaffolds, electrospun fibers, and composites, since the same scaffold type may find application in different tissues. Graphical abstract Cyclodextrins perform as multi‐action structural agents of novel 2D and 3D architectures and endow them with unique cell differentiation and mineral nucleation capabilities and reversible hosting of active substances and cell ligands. Figure. No caption available.

Biodegradable PCL/fibroin/hydroxyapatite porous scaffolds prepared by supercritical foaming for bone regeneration

Regenerative medicine seeks advanced solutions for bone repair in the form of bioactive synthetic scaffolds by using simple and reproducible processing techniques. In this work, poly-ε-caprolactone (PCL)-based porous scaffolds with improved osteoconductive and osteoinductive properties were processed by supercritical foaming through a careful tuning of components and processing conditions. Composite scaffolds were prepared from various combinations of PCL, silk fibroin and nano-hydroxyapatite (nHA). The green and cost-effective supercritical CO2 foaming method applied rendered solid scaffolds with 67-70% porosity. The incorporation of fibroin and nHA in the scaffolds increased the compressive modulus, cellular adhesion and calcium deposition. The composite scaffolds were tested in vivo in a large-scale calvarial defect model, and bone regeneration was evaluated for up to 14 weeks after implantation. Histomorphometric results showed that all implanted constructs gave rise to the endochondral bone formation and unveiled the synergistic effect of silk fibroin and nHA on the bone repair extent. The information gathered may shed light on the design and processing criteria of bioactive bone scaffolds.

Low viscosity-PLGA scaffolds by compressed CO2 foaming for growth factor delivery

Foaming technology using supercritical and compressed fluids has emerged as a promising solution in regenerative medicine for manufacturing porous polymeric scaffolds. Polymers of low inherent viscosity are particularly attractive as scaffold components due to their adequate degradation rate and clearance profiles. However, these polymers lead to scaffolds with limited physical integrity if conventional compressed CO2 foaming is used for their processing. To this end, a modified compressed CO2 foaming method was developed for the processing of mixtures of low inherent viscosity poly(lactic-co-glycolic acid) (PLGA, 0.2 dL g−1) and poly(e-caprolactone) (PCL). The compatibility of the method with the incorporation of growth factors and the role of other admixtures (pregelifed starch) in the scaffold were assessed. Scaffolds were obtained in the form of monoliths and characterized in terms of morphology, physicochemical, and viscoelastic properties; biological tests were carried out to evaluate their ability to promote tissue formation. Scaffolds showed good cell attachment and growth. Results showed that the scaffold composition determined the mechanical and biological performance of the construct and influenced the release profile of the incorporated growth factors.