George Dan Mogoşanu

Natural and synthetic polymers for wounds and burns dressing.

In the last years, health care professionals faced with an increasing number of patients suffering from wounds and burns difficult to treat and heal. During the wound healing process, the dressing protects the injury and contributes to the recovery of dermal and epidermal tissues. Because their biocompatibility, biodegradability and similarity to macromolecules recognized by the human body, some natural polymers such as polysaccharides (alginates, chitin, chitosan, heparin, chondroitin), proteoglycans and proteins (collagen, gelatin, fibrin, keratin, silk fibroin, eggshell membrane) are extensively used in wounds and burns management. Obtained by electrospinning technique, some synthetic polymers like biomimetic extracellular matrix micro/nanoscale fibers based on polyglycolic acid, polylactic acid, polyacrylic acid, poly-ɛ-caprolactone, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, exhibit in vivo and in vitro wound healing properties and enhance re-epithelialization. They provide an optimal microenvironment for cell proliferation, migration and differentiation, due to their biocompatibility, biodegradability, peculiar structure and good mechanical properties. Thus, synthetic polymers are used also in regenerative medicine for cartilage, bone, vascular, nerve and ligament repair and restoration. Biocompatible with fibroblasts and keratinocytes, tissue engineered skin is indicated for regeneration and remodeling of human epidermis and wound healing improving the treatment of severe skin defects or partial-thickness burn injuries.

Usnic acid-loaded biocompatible magnetic PLGA-PVA microsphere thin films fabricated by MAPLE with increased resistance to staphylococcal colonization

Due to their persistence and resistance to the current therapeutic approaches, Staphylococcus aureus biofilm-associated infections represent a major cause of morbidity and mortality in the hospital environment. Since (+)-usnic acid (UA), a secondary lichen metabolite, possesses antimicrobial activity against Gram-positive cocci, including S. aureus, the aim of this study was to load magnetic polylactic-co-glycolic acid-polyvinyl alcohol (PLGA-PVA) microspheres with UA, then to obtain thin coatings using matrix-assisted pulsed laser evaporation and to quantitatively assess the capacity of the bio-nano-active modified surface to control biofilm formation by S. aureus, using a culture-based assay. The UA-loaded microspheres inhibited both the initial attachment of S. aureus to the coated surfaces, as well as the development of mature biofilms. In vitro bioevalution tests performed on the fabricated thin films revealed great biocompatibility, which may endorse them as competitive candidates for the development of improved non-toxic surfaces resistant to S. aureus colonization and as scaffolds for stem cell cultivation and tissue engineering.

Keratin-Based Biomaterials for Biomedical Applications

The ongoing development of manufacturing technologies and of biocompatible and biodegradable polymers have significantly contributed to the progress of drug delivery systems. In the last decades, the knowledge on keratins has significantly increased, regarding their ultrastructure, molecular and cell biology, physiological and pathological roles, as well as their practical applications in the biomedical field. Produced through sustainable, simple and cheap methods, the natural, non-toxic keratin is one of the raw biomaterials frequently used in the pharmaceutical technology for different applications. The purpose of this review is to present the keratins ultrastructure, types, biological distribution, tissue expression profiles, some of their multiple physiological and pathological roles, as well as their practical applications in drug delivery and cellular and tissue engineering.

Anionic polymers and 10nm Fe3O4@UA wound dressings support human foetal stem cells normal development and exhibit great antimicrobial properties

The aims of this study were the development, characterization and bioevaluation of a novel biocompatible, resorbable and bio-active wound dressing prototype, based on anionic polymers (sodium alginate--AlgNa, carboximethylcellulose--CMC) and magnetic nanoparticles loaded with usnic acid (Fe₃O₄@UA). The antimicrobial activity was tested against Staphylococcus aureus grown in biofilms. The biocompatibility testing model included an endothelial cell line from human umbilical vein and human foetal progenitor cells derived from the amniotic fluid, that express a wide spectrum of surface molecules involved in different vascular functions and inflammatory response, and may be used as skin regenerative support. The obtained results demonstrated that CMC/Fe₃O₄@UA and AlgNa/Fe₃O₄@UA are exhibiting structural and functional properties that recommend them for further applications in the biomedical field. They could be used alone or coated with different bio-active compounds, such as Fe₃O₄@UA, for the development of novel, multifunctional porous materials used in tissues regeneration, as antimicrobial substances releasing devices, providing also a mechanical support for the eukaryotic cells adhesion, and exhibiting the advantage of low cytotoxicity on human progenitor cells. The great antimicrobial properties exhibited by the newly synthesized nano-bioactive coatings are recommending them as successful candidates for improving the implanted devices surfaces used in regenerative medicine.

Silver Nanocoatings for Reducing the Exogenous Microbial Colonization of Wound Dressings

The aim of this work was to obtain an antimicrobial coating (NanoAg) for polyester-nylon wound dressings (WDs) for reducing the risk of exogenous wound related infections. The as-prepared NanoAg-WDs were characterized by XRD (X-ray Diffraction), SEM (Scanning Electron Microscopy), TEM (Transmission Electron Microscopy), SAED (Selected Area Electron Diffraction) and IRM (InfraRed Microscopy). Biological characterization consisted of in vitro evaluation of the interaction with fibroblast cell cultures and in vivo biodistribution studies of AgNPs on mice models. Then, specimens of commercial WDs were immersed in a glucose and NaOH solution of silver nanoparticles, followed by the subsequent dropwise addition of AgNO3 solution. The antimicrobial efficiency of the NanoAg-WDs was assessed by in vitro qualitative and quantitative analyses on Staphylococcus aureus and Pseudomonas aeruginosa strains. The in vitro and in vivo studies demonstrated that the tested nanoparticles utilized to coat WDs have a good biocompatibility, allowing the normal development of cultured human cells and revealing a normal biodistribution within a mouse model, without toxic effects. The modified and viable cells count analyses proved that the modified WDs exhibit an improved inhibitory activity of microbial colonization, attachment and biofilm growth. The reported data recommend this type of coatings to obtain modified WDs with antibacterial properties, able to prevent the exogenous microbial contamination of the wound tissue, colonization and further biofilm development.

Calcium Fructoborate for Bone and Cardiovascular Health

Calcium fructoborate (CF), a natural sugar-borate ester found in fresh fruits and vegetables, is a source of soluble boron. CF contains three forms of borate (diester, monoester, and boric acid) and all are biologically active, both at the intracellular (as free boric acid) and extracellular level (as fructose-borate diester and monoester). At the cellular and molecular level, CF is superior to the boric acid/borate, exhibiting a complex “protective” effect against inflammatory response. CF is commercially available in the USA as a “nature-identical” complex, an active compound for dietary supplements. It provides effective and safe support against the discomfort and lack of flexibility associated with osteoarticular conditions (arthritis and joint degeneration), and improves Western Ontario and McMaster Universities Osteoarthritis (WOMAC) and McGill indexes. In addition, orally administered CF is effective in ameliorating symptoms of physiological response to stress, including inflammation of the mucous membranes, discomfort associated with osteoarthritis disorders, and bone loss, and also for supporting cardiovascular health. Clinical studies have exhibited the ability of CF to significantly modulate molecular markers associated with inflammatory mechanisms, mainly on the elevated serum levels of C-reactive protein (CRP).

Prevention of Microbial Communities: Novel Approaches Based Natural Products

Firmly attached to different living or non-living, solid or fluid surfaces rich in nutrients and moisture, microbial biofilm is a matter of great interest due to its major importance for the healthcare community. Depending on common strategies such as mutual protection and hibernation (quiescent bacteria), the resistance, survival and virulence of microbial communities have large implications for human pathology, clinical environment and biomedical devices. The microbial biofilm is continuously changing, stimulating inflammation, increasing vascular permeability and preventing the action of macrophages. About 80% of human infections affecting the gastrointestinal, genitourinary and respiratory systems, oral mucosa and teeth, eyes, middle ear and skin are caused by biofilm-associated microorganisms. Therefore, the search for modern strategies is even more important as microbial biofilms resistant to conventional antibiotics, antiseptics and disinfectants are involved in the frequent treatment failures of some chronic inflammatory diseases and wounds. Natural products containing secondary metabolites, such as aromatic compounds, sulphurated derivatives, terpenoids (essential oils) and alkaloids as quorum-sensing inhibitors and biofilm disruptors, are promising alternatives for the prophylaxis and treatment of chronic infections. Surface modification of medical devices with non-polar functionalized nanoparticles stabilizes the natural compounds antibiofilm activity and inhibits microbial adhesion and biofilm formation and growth for a longer period of time. In this regard, an interdisciplinary approach is needed due to the large number of natural derivatives alone or in combination with biocompatible and biodegradable micro-/ nano-engineered materials.

Bioactive ZnO Coatings Deposited by MAPLE—An Appropriate Strategy to Produce Efficient Anti-Biofilm Surfaces

Deposition of bioactive coatings composed of zinc oxide, cyclodextrin and cefepime (ZnO/CD/Cfp) was performed by the Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The obtained nanostructures were characterized by X-ray diffraction, IR microscopy and scanning electron microscopy. The efficient release of cefepime was correlated with an increased anti-biofilm activity of ZnO/CD/Cfp composites. In vitro and in vivo tests have revealed a good biocompatibility of ZnO/CD/Cfp coatings, which recommend them as competitive candidates for the development of antimicrobial surfaces with biomedical applications. The release of the fourth generation cephalosporin Cfp in a biologically active form from the ZnO matrix could help preventing the bacterial adhesion and the subsequent colonization and biofilm development on various surfaces, and thus decreasing the risk of biofilm-related infections.

Biocompatible hybrid silica nanobiocomposites for the efficient delivery of anti-staphylococcal drugs

This work reports the non-surfactant templated synthesis and characterization of a new tyrosine-silica/antibiotics (TyR-SiO2/ATBs) nanocomposite, as well as both in vitro and in vivo cytotoxicity and antimicrobial activity against the microbial pathogen Staphylococcus aureus. The in vitro microbiological tests proved that the obtained nanobiostructure significantly enhance the antimicrobial activity of three commonly used antibiotics against S. aureus (i.e. erythromycin (ERI), gentamicin (GEN), and cloxacillin (CLO)) as revealed by the increased diameters of the growth inhibition zones and the decreased minimal inhibitory concentration values, as well as by the inhibitory effect of sub-lethal antibiotic concentrations on the ability of the respective pathogenic strains to adhere and colonize different substrata. These results, correlated with the lack of toxicity against mesenchymal stem cells along with an appropriate in vivo biodistribution highlight the promising therapeutic potential of this carrier that allows a decrease of the required active doses while significantly lessening the harmful side effects of the medication on the host organism.

Prosthetic Devices with Nanostructurated Surfaces for Increased Resistance to Microbial Colonization

This review highlights and discusses the impact of nanotechnology on the inhibition of microbial colonization and biofilm development on modified surface prosthetic devices. In the first part of the paper the current status of infections related to prosthetic devices and the inquiries resulting from the increased number of patients with these infections are briefly reviewed. Next we discuss several aspects about the implication of nanotechnology in prosthetic devices surface modification and its impact on the prevention of infections. The main aspects regarding the biocompatibility and the application of these nanomodified prosthetic devices in tissue engineering are also highlighted.