Antitumoral-Embedded Biopolymeric Spheres for Implantable Devices.

The bioactive surface modification of implantable devices paves the way towards the personalized healthcare practice by providing a versatile and tunable approach that increase the patient outcome, facilitate the medical procedure, and reduce the indirect or secondary effects. The purpose of our study was to assess the performance of composite coatings based on biopolymeric spheres of poly(lactide-co-glycolide) embedded with hydroxyapatite (HA) and methotrexate (MTX). Bio-simulated tests performed for up to one week evidenced the gradual release of the antitumor drug and the biomineralization potential of PLGA/HA-MTX sphere coatings. The composite materials proved superior biocompatibility and promoted enhanced cell adhesion and proliferation with respect to human preosteoblast and osteosarcoma cell lines when compared to pristine titanium.

Infection-Free and Enhanced Wound Healing Potential of Alginate Gels Incorporating Silver and Tannylated Calcium Peroxide Nanoparticles.

The treatment of chronic wounds involves precise requirements and complex challenges, as the healing process cannot go beyond the inflammatory phase, therefore increasing the healing time and implying a higher risk of opportunistic infection. Following a better understanding of the healing process, oxygen supply has been validated as a therapeutic approach to improve and speed up wound healing. Moreover, the local implications of antimicrobial agents (such as silver-based nano-compounds) significantly support the normal healing process, by combating bacterial contamination and colonization. In this study, silver (S) and tannylated calcium peroxide (CaO2@TA) nanoparticles were obtained by adapted microfluidic and precipitation synthesis methods, respectively. After complementary physicochemical evaluation, both types of nanoparticles were loaded in (Alg) alginate-based gels that were further evaluated as possible dressings for wound healing. The obtained composites showed a porous structure and uniform distribution of nanoparticles through the polymeric matrix (evidenced by spectrophotometric analysis and electron microscopy studies), together with a good swelling capacity. The as-proposed gel dressings exhibited a constant and suitable concentration of released oxygen, as shown for up to eight hours (UV-Vis investigation). The biofilm modulation data indicated a synergistic antimicrobial effect between silver and tannylated calcium peroxide nanoparticles, with a prominent inhibitory action against the Gram-positive bacterial biofilm after 48 h. Beneficial effects in the human keratinocytes cultured in contact with the obtained materials were demonstrated by the performed tests, such as MTT, LDH, and NO.

Nanostructured Coatings Based on Graphene Oxide for the Management of Periprosthetic Infections.

To modulate the bioactivity and boost the therapeutic outcome of implantable metallic devices, biodegradable coatings based on polylactide (PLA) and graphene oxide nanosheets (nGOs) loaded with Zinforo™ (Zin) have been proposed in this study as innovative alternatives for the local management of biofilm-associated periprosthetic infections. Using a modified Hummers protocol, high-purity and ultra-thin nGOs have been obtained, as evidenced by X-ray diffraction (XRD) and transmission electron microscopy (TEM) investigations. The matrix-assisted pulsed laser evaporation (MAPLE) technique has been successfully employed to obtain the PLA-nGO-Zin coatings. The stoichiometric and uniform transfer was revealed by infrared microscopy (IRM) and scanning electron microscopy (SEM) studies. In vitro evaluation, performed on fresh blood samples, has shown the excellent hemocompatibility of PLA-nGO-Zin-coated samples (with a hemolytic index of 1.15%), together with their anti-inflammatory ability. Moreover, the PLA-nGO-Zin coatings significantly inhibited the development of mature bacterial biofilms, inducing important anti-biofilm efficiency in the as-coated samples. The herein-reported results evidence the promising potential of PLA-nGO-Zin coatings to be used for the biocompatible and antimicrobial surface modification of metallic implants.

Microwave-Assisted Silanization of Magnetite Nanoparticles Pre-Synthesized by a 3D Microfluidic Platform.

Magnetite nanoparticles (Fe3O4 NPs) are among the most investigated nanomaterials, being recognized for their biocompatibility, versatility, and strong magnetic properties. Given that their applicability depends on their dimensions, crystal morphology, and surface chemistry, Fe3O4 NPs must be synthesized in a controlled, simple, and reproducible manner. Since conventional methods often lack tight control over reaction parameters and produce materials with unreliable characteristics, increased scientific interest has been directed to microfluidic techniques. In this context, the present paper describes the development of an innovative 3D microfluidic platform suitable for synthesizing uniform Fe3O4 NPs with fine-tuned properties. On-chip co-precipitation was performed, followed by microwave-assisted silanization. The obtained nanoparticles were characterized from the compositional and microstructural perspectives by X-ray diffraction (XRD) and transmission electron microscopy (TEM). Moreover, supplementary physicochemical investigations, such as Fourier Transform Infrared Spectroscopy (FT-IR), Kaiser Test, Ultraviolet-Visible (UV-Vis) Spectrophotometry, Dynamic Light Scattering (DLS), and Thermogravimetry and Differential Scanning Calorimetry (TG-DSC) analyses, demonstrated the successful surface modification. Considering the positive results, the presented synthesis and functionalization method represents a fast, reliable, and effective alternative for producing tailored magnetic nanoparticles.

A Microfluidic Approach for Synthesis of Silver Nanoparticles as a Potential Antimicrobial Agent in Alginate-Hyaluronic Acid-Based Wound Dressings.

The recognized antimicrobial activity of silver nanoparticles is a well-studied property, especially when designing and developing biomaterials with medical applications. As biological activity is closely related to the physicochemical characteristics of a material, aspects such as particle morphology and dimension should be considered. Microfluidic systems in continuous flow represent a promising method to control the size, shape, and size distribution of synthesized nanoparticles. Moreover, using microfluidics widens the synthesis options by creating and controlling parameters that are otherwise difficult to maintain in conventional batch procedures. This study used a microfluidic platform with a cross-shape design as an innovative method for synthesizing silver nanoparticles and varied the precursor concentration and the purging speed as experimental parameters. The compositional and microstructural characterization of the obtained samples was carried out by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Four formulations of alginate-based hydrogels with the addition of hyaluronic acid and silver nanoparticles were obtained to highlight the antimicrobial activity of silver nanoparticles and the efficiency of such a composite in wound treatment. The porous structure, swelling capacity, and biological properties were evaluated through physicochemical analysis (FT-IR and SEM) and through contact with prokaryotic and eukaryotic cells. The results of the physicochemical and biological investigations revealed desirable characteristics for performant wound dressings (i.e., biocompatibility, appropriate porous structure, swelling rate, and degradation rate, ability to inhibit biofilm formation, and cell growth stimulation capacity), and the obtained materials are thus recommended for treating chronic and infected wounds.

Electrospun Fibrous Silica for Bone Tissue Engineering Applications.

The production of highly porous and three-dimensional (3D) scaffolds with biomimicking abilities has gained extensive attention in recent years for tissue engineering (TE) applications. Considering the attractive and versatile biomedical functionality of silica (SiO2) nanomaterials, we propose herein the development and validation of SiO2-based 3D scaffolds for TE. This is the first report on the development of fibrous silica architectures, using tetraethyl orthosilicate (TEOS) and polyvinyl alcohol (PVA) during the self-assembly electrospinning (ES) processing (a layer of flat fibers must first be created in self-assembly electrospinning before fiber stacks can develop on the fiber mat). The compositional and microstructural characteristics of obtained fibrous materials were evaluated by complementary techniques, in both the pre-ES aging period and post-ES calcination. Then, in vivo evaluation confirmed their possible use as bioactive scaffolds in bone TE.

H2O2-PLA-(Alg)2Ca Hydrogel Enriched in Matrigel® Promotes Diabetic Wound Healing.

Hydrogel-based dressings exhibit suitable features for successful wound healing, including flexibility, high water-vapor permeability and moisture retention, and exudate absorption capacity. Moreover, enriching the hydrogel matrix with additional therapeutic components has the potential to generate synergistic results. Thus, the present study centered on diabetic wound healing using a Matrigel-enriched alginate hydrogel embedded with polylactic acid (PLA) microspheres containing hydrogen peroxide (H2O2). The synthesis and physicochemical characterization of the samples, performed to evidence their compositional and microstructural features, swelling, and oxygen-entrapping capacity, were reported. For investigating the three-fold goal of the designed dressings (i.e., releasing oxygen at the wound site and maintaining a moist environment for faster healing, ensuring the absorption of a significant amount of exudate, and providing biocompatibility), in vivo biological tests on wounds of diabetic mice were approached. Evaluating multiple aspects during the healing process, the obtained composite material proved its efficiency for wound dressing applications by accelerating wound healing and promoting angiogenesis in diabetic skin injuries.

Overview of Antimicrobial Biodegradable Polyester-Based Formulations.

As the clinical complications induced by microbial infections are known to have life-threatening side effects, conventional anti-infective therapy is necessary, but not sufficient to overcome these issues. Some of their limitations are connected to drug-related inefficiency or resistance and pathogen-related adaptive modifications. Therefore, there is an urgent need for advanced antimicrobials and antimicrobial devices. A challenging, yet successful route has been the development of new biostatic or biocide agents and biomaterials by considering the indisputable advantages of biopolymers. Polymers are attractive materials due to their physical and chemical properties, such as compositional and structural versatility, tunable reactivity, solubility and degradability, and mechanical and chemical tunability, together with their intrinsic biocompatibility and bioactivity, thus enabling the fabrication of effective pharmacologically active antimicrobial formulations. Besides representing protective or potentiating carriers for conventional drugs, biopolymers possess an impressive ability for conjugation or functionalization. These aspects are key for avoiding malicious side effects or providing targeted and triggered drug delivery (specific and selective cellular targeting), and generally to define their pharmacological efficacy. Moreover, biopolymers can be processed in different forms (particles, fibers, films, membranes, or scaffolds), which prove excellent candidates for modern anti-infective applications. This review contains an overview of antimicrobial polyester-based formulations, centered around the effect of the dimensionality over the properties of the material and the effect of the production route or post-processing actions.

Silver/Graphene Oxide Nanostructured Coatings for Modulating the Microbial Susceptibility of Fixation Devices Used in Knee Surgery.

Exploring silver-based and carbon-based nanomaterials' excellent intrinsic antipathogenic effects represents an attractive alternative for fabricating anti-infective formulations. Using chemical synthesis protocols, stearate-conjugated silver (Ag@C18) nanoparticles and graphene oxide nanosheets (nGOs) were herein obtained and investigated in terms of composition and microstructure. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) characterizations revealed the formation of nanomaterials with desirable physical properties, while X-ray diffraction (XRD) analyses confirmed the high purity of synthesized nanomaterials. Further, laser-processed Ag@C18-nGO coatings were developed, optimized, and evaluated in terms of biological and microbiological outcomes. The highly biocompatible Ag@C18-nGO nanostructured coatings proved suitable candidates for the local modulation of biofilm-associated periprosthetic infections.

MAPLE Processed Nanostructures for Antimicrobial Coatings.

Despite their great benefits for debilitated patients, indwelling devices are prone to become easily colonized by resident and opportunistic microorganisms, which have the ability to attach to their surfaces and form highly specialized communities called biofilms. These are extremely resistant to host defense mechanisms and antibiotics, leading to treatment failure and device replacement, but also to life-threatening complications. In this study, we aimed to optimize a silica (SiO2)-coated magnetite (Fe3O4)-based nanosystem containing the natural antimicrobial agent, eugenol (E), suitable for MAPLE (matrix-assisted pulsed laser evaporation) deposition as a bioactive coating for biomedical applications. X-ray diffraction, thermogravimetric analysis, Fourier-transform infrared spectroscopy, and transmission electron microscopy investigations were employed to characterize the obtained nanosystems. The in vitro tests evidenced the superior biocompatibility of such nanostructured coatings, as revealed by their non-cytotoxic activity and ability to promote cellular proliferation and sustain normal cellular development of dermal fibroblasts. Moreover, the obtained nanocoatings did not induce proinflammatory events in human blood samples. Our studies demonstrated that Fe3O4 NPs can improve the antimicrobial activity of E, while the use of a SiO2 matrix may increase its efficiency over prolonged periods of time. The Fe3O4@SiO2 nanosystems showed excellent biocompatibility, sustaining human dermal fibroblasts' viability, proliferation, and typical architecture. More, the novel coatings lack proinflammatory potential as revealed by the absence of proinflammatory cytokine expression in response to human blood sample interactions.

Inorganic Nanoparticles in Bone Healing Applications.

Modern biomedicine aims to develop integrated solutions that use medical, biotechnological, materials science, and engineering concepts to create functional alternatives for the specific, selective, and accurate management of medical conditions. In the particular case of tissue engineering, designing a model that simulates all tissue qualities and fulfills all tissue requirements is a continuous challenge in the field of bone regeneration. The therapeutic protocols used for bone healing applications are limited by the hierarchical nature and extensive vascularization of osseous tissue, especially in large bone lesions. In this regard, nanotechnology paves the way for a new era in bone treatment, repair and regeneration, by enabling the fabrication of complex nanostructures that are similar to those found in the natural bone and which exhibit multifunctional bioactivity. This review aims to lay out the tremendous outcomes of using inorganic nanoparticles in bone healing applications, including bone repair and regeneration, and modern therapeutic strategies for bone-related pathologies.

Bioactive Coatings Loaded with Osteogenic Protein for Metallic Implants.

Osteoconductive and osteoinductive coatings represent attractive and tunable strategies towards the enhanced biomechanics and osseointegration of metallic implants, providing accurate local modulation of bone-to-implant interface. Composite materials based on polylactide (PLA) and hydroxyapatite (HAp) are proved beneficial substrates for the modulation of bone cells' development, being suitable mechanical supports for the repair and regeneration of bone tissue. Moreover, the addition of osteogenic proteins represents the next step towards the fabrication of advanced biomaterials for hard tissue engineering applications, as their regulatory mechanisms beneficially contribute to the new bone formation. In this respect, laser-processed composites, based on PLA, Hap, and bone morphogenetic protein 4(BMP4), are herein proposed as bioactive coatings for metallic implants. The nanostructured coatings proved superior ability to promote the adhesion, viability, and proliferation of osteoprogenitor cells, without affecting their normal development and further sustaining the osteogenic differentiation of the cells. Our results are complementary to previous studies regarding the successful use of chemically BMP-modified biomaterials in orthopedic and orthodontic applications.

Composite P(3HB-3HV)-CS Spheres for Enhanced Antibiotic Efficiency.

Natural-derived biopolymers are suitable candidates for developing specific and selective performance-enhanced antimicrobial formulations. Composite polymeric particles based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and chitosan, P(3HB-3HV)-CS, are herein proposed as biocompatible and biodegradable delivery systems for bioproduced antibiotics: bacitracin (Bac), neomycin (Neo) and kanamycin (Kan). The stimuli-responsive spheres proved efficient platforms for boosting the antibiotic efficiency and antibacterial susceptibility, as evidenced against Gram-positive and Gram-negative strains. Absent or reduced proinflammatory effects were evidenced on macrophages in the case of Bac-/Neo- and Kan-loaded spheres, respectively. Moreover, these systems showed superior ability to sustain and promote the proliferation of dermal fibroblasts, as well as to preserve their ultrastructure (membrane and cytoskeleton integrity) and to exhibit anti-oxidant activity. The antibiotic-loaded P(3HB-3HV)-CS spheres proved efficient alternatives for antibacterial strategies.

MAPLE Coatings Embedded with Essential Oil-Conjugated Magnetite for Anti-Biofilm Applications.

The present study reports on the development and evaluation of nanostructured composite coatings of polylactic acid (PLA) embedded with iron oxide nanoparticles (Fe3O4) modified with Eucalyptus (Eucalyptus globulus) essential oil. The co-precipitation method was employed to synthesize the magnetite particles conjugated with Eucalyptus natural antibiotic (Fe3O4@EG), while their composition and microstructure were investigated using grazing incidence X-ray diffraction (GIXRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The matrix-assisted pulsed laser evaporation (MAPLE) technique was further employed to obtain PLA/Fe3O4@EG thin films. Optimal experimental conditions for laser processing were established by complementary infrared microscopy (IRM) and scanning electron microscopy (SEM) investigations. The in vitro biocompatibility with eukaryote cells was proven using mesenchymal stem cells, while the anti-biofilm efficiency of composite PLA/Fe3O4@EG coatings was assessed against Gram-negative and Gram-positive pathogens.

Bioactive Ibuprofen-Loaded PLGA Coatings for Multifunctional Surface Modification of Medical Devices.

To modulate the biofunctionality of implantable medical devices commonly used in clinical practice, their surface modification with bioactive polymeric coatings is an attractive and successful emerging strategy. Biodegradable coatings based on poly(lactic acid-co-glycolic acid), PLGA, represent versatile and safe candidates for surface modification of implantable biomaterials and devices, providing additional tunable ability for topical delivery of desired therapeutic agents. In the present study, Ibuprofen-loaded PLGA coatings (PLGA/IBUP) were obtained by using the dip-coating and drop-casting combined protocol. The composite materials demonstrated long-term drug release under biologically simulated dynamic conditions. Reversible swelling phenomena of polymeric coatings occurred in the first two weeks of testing, accompanied by the gradual matrix degradation and slow release of the therapeutic agent. Irreversible degradation of PLGA coatings occurred after one month, due to copolymer's hydrolysis (evidenced by chemical and structural modifications). After 30 days of dynamic testing, the cumulative release of IBUP was ~250 µg/mL. Excellent cytocompatibility was revealed on human-derived macrophages, fibroblasts and keratinocytes. The results herein evidence the promising potential of PLGA/IBUP coatings to be used for surface modification of medical devices, such as metallic implants and wound dressings.

Bioactive Coatings Based on Hydroxyapatite, Kanamycin, and Growth Factor for Biofilm Modulation.

The occurrence of opportunistic local infections and improper integration of metallic implants results in severe health conditions. Protective and tunable coatings represent an attractive and challenging selection for improving the metallic devices' biofunctional performances to restore or replace bone tissue. Composite materials based on hydroxyapatite (HAp), Kanamycin (KAN), and fibroblast growth factor 2 (FGF2) are herein proposed as multifunctional coatings for hard tissue implants. The superior cytocompatibility of the obtained composite coatings was evidenced by performing proliferation and morphological assays on osteoblast cell cultures. The addition of FGF2 proved beneficial concerning the metabolic activity, adhesion, and spreading of cells. The KAN-embedded coatings exhibited significant inhibitory effects against bacterial biofilm development for at least two days, the results being superior in the case of Gram-positive pathogens. HAp-based coatings embedded with KAN and FGF2 protein are proposed as multifunctional materials with superior osseointegration potential and the ability to reduce device-associated infections.

An Updated Review on Silver Nanoparticles in Biomedicine.

Silver nanoparticles (AgNPs) represent one of the most explored categories of nanomaterials for new and improved biomaterials and biotechnologies, with impressive use in the pharmaceutical and cosmetic industry, anti-infective therapy and wound care, food and the textile industry. Their extensive and versatile applicability relies on the genuine and easy-tunable properties of nanosilver, including remarkable physicochemical behavior, exceptional antimicrobial efficiency, anti-inflammatory action and antitumor activity. Besides commercially available and clinically safe AgNPs-based products, a substantial number of recent studies assessed the applicability of nanosilver as therapeutic agents in augmented and alternative strategies for cancer therapy, sensing and diagnosis platforms, restorative and regenerative biomaterials. Given the beneficial interactions of AgNPs with living structures and their nontoxic effects on healthy human cells, they represent an accurate candidate for various biomedical products. In the present review, the most important and recent applications of AgNPs in biomedical products and biomedicine are considered.

Long-Term Evaluation of Dip-Coated PCL-Blend-PEG Coatings in Simulated Conditions.

Our study focused on the long-term degradation under simulated conditions of coatings based on different compositions of polycaprolactone-polyethylene glycol blends (PCL-blend-PEG), fabricated for titanium implants by a dip-coating technique. The degradation behavior of polymeric coatings was evaluated by polymer mass loss measurements of the PCL-blend-PEG during immersion in SBF up to 16 weeks and correlated with those yielded from electrochemical experiments. The results are thoroughly supported by extensive compositional and surface analyses (FTIR, GIXRD, SEM, and wettability investigations). We found that the degradation behavior of PCL-blend-PEG coatings is governed by the properties of the main polymer constituents: the PEG solubilizes fast, immediately after the immersion, while the PCL degrades slowly over the whole period of time. Furthermore, the results evidence that the alteration of blend coatings is strongly enhanced by the increase in PEG content. The biological assessment unveiled the beneficial influence of PCL-blend-PEG coatings for the adhesion and spreading of both human-derived mesenchymal stem cells and endothelial cells.

Bioactive Surfaces of Polylactide and Silver Nanoparticles for the Prevention of Microbial Contamination.

Thanks to its peculiar interactions with biological molecules and structures, metallic silver in the form of silver nanoparticles achieved a remarkable comeback as a potential antimicrobial agent. The antimicrobial use of silver nanoparticles is of clinical importance, as several pathogenic microorganisms developed resistance against various conventional drug treatments. Hence, given the extensive efficiency of silver nanoparticles against drug-sensitive and drug-resistant pathogens, their therapeutic implications were demonstrated in multiple medical applications, such as silver-based dressings, silver-coated biomedical devices and silver-containing nanogels. Bacterial strains possess an intrinsic ability to form well-organized microbial communities, capable of developing adaptive mechanisms to environmental aggression and self-protective pathways against antibiotics. The formation of these mono- or poly-microbial colonies, called biofilms, is closely related with the occurrence of infectious processes which result in severe and chronic pathologies. Therefore, substantial efforts were oriented to the development of new protective coatings for biomedical surfaces, capable of sustaining the physiological processes within human-derived normal cells and to disrupt the microbial contamination and colonization stages. Nanostructured materials based on polylactic acid and silver nanoparticles are herein proposed as bioactive coatings able to prevent the formation of microbial biofilms on biomedical relevant surfaces.

Biodistribution of essential oil-conjugated silver nanoparticles.

The beneficial synergy between antimicrobial silver nanoparticles (AgNPs) and essential oils (EOs), with therapeutic effects that have been acknowledged and explored for a long time, opens the way towards developing new and promising alternatives for anti-infective therapies. With the aim to improve the cytocompatibility and stability of AgNPs and to overcome the volatilization of EOs, AgNPs conjugated with sage (Salvia officinalis) and cinnamon (Cinnamomum aromaticum) EOs were obtained in our study. The synthesis process was realized either by classical or ultrasound-assisted chemical reduction. Compositional and microstructural characterization of the as-obtained Ag@EO NPs was performed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The biodistribution of Ag@EO NPs was evaluated on a mouse animal model.