Martín F. Desimone

Silica-collagen bionanocomposites as three-dimensional scaffolds for fibroblast immobilization.

Silica-collagen bionanocomposite hydrogels were obtained by addition of silica nanoparticles to a protein suspension followed by neutralization. Electron microscopy studies indicated that larger silica nanoparticles (80 nm) do not interact strongly with collagen, whereas smaller ones (12 nm) form rosaries along the protein fibers. However, the composite network structurally evolved with time due to the contraction of the cells and the dissolution of the silica nanoparticles. When compared to classical collagen hydrogels, these bionanocomposite materials showed lower surface contraction in the short term (1 week) and higher viability of entrapped cells in the long term (3 weeks). A low level of gelatinase MMP2 enzyme expression was also found after this period. Several proteins involved in the catabolic and anabolic activity of the cells could also be observed by immunodetection techniques. All these data suggest that the bionanocomposite matrices constitute a suitable environment for fibroblast adhesion, proliferation and biological activity and therefore constitute an original three-dimensional environment for in vitro cell culture and in vivo applications, in particular as biological dressings.

Fibroblast encapsulation in hybrid silica–collagen hydrogels

Silica–collagen scaffolds are synthesized by the simultaneous polymerization of aqueous silicates and self-assembly of protein triple helices in the presence of living human dermal fibroblasts.

Antibiotic-loaded silica nanoparticle–collagen composite hydrogels with prolonged antimicrobial activity for wound infection prevention

Silica-collagen type I nanocomposite hydrogels are evaluated as medicated dressings to prevent infection in chronic wounds. Two antibiotics, gentamicin and rifamycin, are encapsulated in a single step within plain silica nanoparticles. Their antimicrobial efficiency against Pseudomonas aeruginosa and Staphylococcus aureus is assessed. Gentamycin-loaded 500 nm particles can be immobilized at high silica dose in concentrated collagen hydrogels without modifying their fibrillar structure or impacting on their rheological behavior and increases their proteolytic stability. Gentamicin release from the nanocomposites is sustained over 7 days, offering an unparalleled prolonged antibacterial activity. Particle immobilization also decreases their cytotoxicity towards surface-seeded fibroblast cells. Rifamycin-loaded 100 nm particles significantly alter the collagen hydrogel structure at high silica doses. The thus-obtained nanocomposites show no antibacterial efficiency, due to strong adsorption of rifamycin on collagen fibers. The complex interplay of interactions between drugs, silica and collagen is a key factor regulating the properties of these composite hydrogels as antibiotic-delivering biological dressings and must be taken into account for future extension to other wound healing agents.

Ethanol tolerance in free and sol-gel immobilised Saccharomyces cerevisiae

The tolerance of sol-gel immobilised and free Saccharomyces cerevisiae to ethanol was studied. The effects of ethanol preincubation time showed that the specific death velocity decreased from 2×105 c.f.u. min−1 for free cells to 2×104 c.f.u. min−1 for immobilised cells thus indicating that immobilised yeast was far less sensitive to the ethanol damage. The specific glucose consumption of immobilised and free cells on a per cell basis was 3×10−12 g cell−1 h−1 and 9×10−12 g cell−1 h−1, respectively.

Bio-inspired silica–collagen materials: applications and perspectives in the medical field

Silica and collagen are two of the most abundant substances in the Earths geosphere and biosphere, respectively. Yet, their close association in nature has never been clearly demonstrated despite increasing evidence for the key role of silicon in mammalians. Foreseeing the therapeutic benefits of their association within composites or hybrids, a wide diversity of bio-inspired silica-collagen materials have been prepared over nearly 15 years. These works not only generated materials with a large range of structures and properties, from soft mineralized hydrogels to hard compact xerogels, but also provided more fundamental information about the interplay between polymer self-assembly processes and inorganic condensation mechanisms. Biological in vitro and in vivo evaluations suggest their bioactivity, cyto- and biocompatibility as well as controlled drug delivery properties. Hence they can now fully integrate the family of materials with high potential for the development of innovative biomedical devices.

In vitro Studies and Preliminary In vivo Evaluation of Silicified Concentrated Collagen Hydrogels

Hybrid and nanocomposite silica-collagen materials derived from concentrated collagen hydrogels were evaluated in vitro and in vivo to establish their potentialities for biological dressings. Silicification significantly improved the mechanical and thermal stability of the collagen network within the hybrid systems. Nanocomposites were found to favor the metabolic activity of immobilized human dermal fibroblasts while decreasing the hydrogel contraction. Cell adhesion experiments suggested that in vitro cell behavior was dictated by mechanical properties and surface structure of the scaffold. First-to-date in vivo implantation of bulk hydrogels in subcutaneous sites of rats was performed over the vascular inflammatory period. These materials were colonized and vascularized without inducing strong inflammatory response. These data raise reasonable hope for the future application of silica-collagen biomaterials as biological dressings.

A functional material that combines the Cr(VI) reduction activity of Burkholderia sp. with the adsorbent capacity of sol–gel materials

In the present work, Cr(VI) reduction in aqueous as well as in soil environments has been studied using free and sol–gel immobilized Burkholderia sp. Enhanced reduction rates were achieved by immobilized cells, which are found to be protected from the deleterious effects of high Cr(VI) concentrations. Immobilized bacteria showed enhanced performance in comparison with free cells because of the combination of bacteria biotransformation effect and chromium adsorption on silica matrices. Moreover, bacteria did not lose any activity after four cycles of reutilization. Bacteria immobilized in silica matrices had the ability to completely reduce 100 µg ml−1Cr(VI) after 4 days of incubation in aqueous media and to transform 200 µg ml−1Cr(VI) after 7 days in sterile soil. Immobilized bacteria demonstrated highly efficient Cr(VI) reduction over the Cr(VI) concentration range 50–500 µg g−1 and 200–800 µg g−1 in aqueous and soil environments, respectively. These results highlight the potential of this functional material that combines the biological activity of bacterial cells with the adsorbent capacity of sol–gel materials.

Development of Sol-Gel Hybrid Materials for Whole Cell Immobilization

The development of a good biocompatible matrix for immobilization of cells is very crucial for improving the performance of functional biohybrids. The synthesis of solid inorganic materials from alkoxide, aqueous and polyol-modified silanes routes, as well as the incorporation of organic polymers, are further areas being developed to improve the viability of encapsulated cells. This emerging field of material science has generated considerable and increasing interest during the past decade. Recent advances in the field involving biomaterials, biohybrids, and functional nanomaterials provided novel materials, which have gained the attention of the scientific community, Governments and industrial companies. Overall, this review is intended to give an overview on the current state of the art of the patents associated to the immobilization of whole living cells in sol-gel derived hybrid materials and to describe the major challenges to be addressed in the forthcoming years.

Recent patents on the synthesis and application of silica nanoparticles for drug delivery.

Drug delivery systems are designed to improve therapy efficacy as well as patient compliance. This could be accomplished by specifically targeting a medication intact to its active site, therefore reducing side-effects and enabling high local drug concentrations. Silica nanoparticles have gained ground in the biomedical field for their biocompatibility and biodegradability, being themselves inert and stable, thus enabling a variety of formulation designs for application in the pharmaceutical industry. This paper is a review of the recent patents on the applications of silica nanoparticles for drug delivery and their preparation. The review will focus on the different techniques available to obtain silica nanoparticles with variable morphology and their drug targeting applications, providing an overview of silica particles synthesis described in the literature.

Sol-gel Encapsulation of Biomolecules and Cells for Medicinal Applications

The sol-gel process provides a robust and versatile technology for the immobilization of biologicals. A wide range of inorganic, composites and hybrid materials can be prepared to encapsulate molecular drugs, proteins, antibodies/antigens, enzymes, nucleic acids, prokaryotic and eukaryotic cells into bulk gels, particles and films. This review describes the applications of sol-gel encapsulation relevant to medicinal chemistry focusing on the recent development of biosensors as well as systems for production, screening and delivery of bioactive compounds and biomaterials.