Developing Antibiofilm Fibrillar Scaffold with Intrinsic Capacity to Produce Silver Nanoparticles.

The development of biomedical systems with antimicrobial and antibiofilm properties is a difficult medical task for preventing bacterial adhesion and growth on implanted devices. In this work, a fibrillar scaffold was produced by electrospinning a polymeric organic dispersion of polylactic acid (PLA) and poly(α,ß-(N-(3,4-dihydroxyphenethyl)-L-aspartamide-co-α,ß-N-(2-hydroxyethyl)-L-aspartamide) (PDAEA). The pendant catechol groups of PDAEA were used to reduce silver ions in situ and produce silver nanoparticles onto the surface of the electrospun fibers through a simple and reproducible procedure. The morphological and physicochemical characterization of the obtained scaffolds were studied and compared with virgin PLA electrospun sample. Antibiofilm properties against Pseudomonas aeruginosa, used as a biofilm-forming pathogen model, were also studied on planar and tubular scaffolds. These last were fabricated as a proof of concept to demonstrate the possibility to obtain antimicrobial devices with different shape and dimension potentially useful for different biomedical applications. The results suggest a promising approach for the development of antimicrobial and antibiofilm scaffolds.

Imatinib-Loaded Micelles of Hyaluronic Acid Derivatives for Potential Treatment of Neovascular Ocular Diseases.

In this work, new micellar systems able to cross corneal barrier and to improve the permeation of imatinib free base were prepared and characterized. HA-EDA-C16, HA-EDA-C16-PEG, and HA-EDA-C16-CRN micelles were synthesized starting from hyaluronic acid (HA), ethylenediamine (EDA), hexadecyl chains (C16), polyethylene glycol (PEG), or l-carnitine (CRN). These nanocarriers showed optimal particle size and mucoadhesive properties. Imatinib-loaded micelles were able to interact with corneal barrier and to promote imatinib transcorneal permeation and penetration. In addition, a study was conducted to understand the in vitro imatinib inhibitory effect on a choroidal neovascularization process. Imatinib released from polymeric micelles was able to inhibit endothelial cell sprouting and to promote cell tube disruption.

Double-Network-Structured Graphene Oxide-Containing Nanogels as Photothermal Agents for the Treatment of Colorectal Cancer.

Here, we reported the production of hyaluronic acid/polyaspartamide-based double-network nanogels for the potential treatment of colorectal carcinoma. Graphene oxide, thanks to the huge aromatic surface area, allows to easily load high amount of irinotecan (33.0% w/w) and confers to the system hyperthermic properties when irradiated with a near-infrared (NIR) laser beam. We demonstrate that the release of antitumor drug is influenced both by the pH of the external medium and the NIR irradiation process. In vitro biological studies, conducted on human colon cancer cells (HCT 116), revealed that nanogels are uptaken by the cancer cells and, in the presence of the antitumor drug, can produce a synergistic hyperthermic/cytotoxic effect. Finally, 3D experiments demonstrate that it is possible to conduct thermal ablation of solid tumors after the intratumoral administration of nanogels.

A methacrylic hyaluronic acid derivative for potential application in oral treatment of celiac disease.

OBJECTIVE: Aim of this work was the synthesis of a methacrylic hyaluronic acid (HA) derivative and the production, via photocrosslinking, of related hydrogels loaded with an endopeptidase intended for a potential oral treatment of celiac disease. METHODS: The methacrylic derivative of HA was prepared through a one-pot procedure involving the reaction with ethylenediamine (EDA) and methacrylic anhydride (MA). The obtained derivative, named HA-EDA-MA, was used to prepare photocrosslinked hydrogels loaded with a prolyl endopeptidase derived from Flavobacterium meningosepticum (PEP FM) able to detoxify gliadin. Obtained hydrogels were recovered as gels or freeze-dried powders. RESULTS: Hydrogels obtained as freeze-dried powders, are able to protect loaded enzyme from degradation due to freeze-drying process and from alteration during storage, overall in the presence of a cryoprotectant. All photocrosslinked HA-EDA-MA hydrogels (gels and powders) release PEP FM in simulated intestinal fluid in sustained manner and in active form. HA-EDA-MA hydrogels are nontoxic as demonstrated through in vitro studies on BALB 3T3 cells. CONCLUSIONS: Prepared hydrogels show a potential application for oral treatment of celiac disease thanks to the possibility to release enzymes able to detoxify the gliadin peptide that induces the immunogenic response.

Gellan gum-dopamine mediated in situ synthesis of silver nanoparticles and development of nano/micro-composite injectable hydrogel with antimicrobial activity.

Infected skin wounds represent a serious health threat due to the long healing process and the risk of colonization by multi-drug-resistant bacteria. Silver nanoparticles (AgNPs) have shown broad-spectrum antimicrobial activity. This study introduces a novel approach to address the challenge of infected skin wounds by employing gellan gum-dopamine (GG-DA) as a dual-functional agent, serving both as a reducing and capping agent, for the in situ green synthesis of silver nanoparticles. Unlike previous methods, this work utilizes a spray-drying technique to convert the dispersion of GG-DA and AgNPs into microparticles, resulting in nano-into-micro systems (AgNPs@MPs). The microparticles, with an average size of approximately 3 µm, embed AgNPs with a 13 nm average diameter. Furthermore, the study explores the antibacterial efficacy of these AgNPs@MPs directly and in combination with other materials against gram-positive and gram-negative bacteria. The versatility of the antimicrobial material is showcased by incorporating the microparticles into injectable hydrogels. These hydrogels, based on oxidized Xanthan Gum (XGox) and a hyperbranched synthetic polymer (HB10K-G5-alanine), are designed with injectability and self-healing properties through Shiff base formation. The resulting nano-into-micro-into-macro hybrid hydrogel emerges as a promising biomedical solution, highlighting the multifaceted potential of this innovative approach in wound care and infection management.

Biotinylated polyaminoacid-based nanoparticles for the targeted delivery of lenvatinib towards hepatocarcinoma.

In this work, we describe the development of targeted polymeric nanoparticles loaded with lenvatinib for the treatment of hepatocellular carcinoma (HCC). A synthetic brush copolymer (PHEA-g-BIB-pButMA-g-PEG-biotin) was synthesized from α-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) by a three-step reaction involving atom transfer radical polymerisation (ATRP) to graft hydrophobic polybutylmethacrylate pendant groups and further conjugation with biotinylated polyethylene glycol via carbonate ester. Subsequently, lenvatinib-loaded nanoparticles were obtained and characterized demonstrating colloidal size, negative zeta potential, biotin exposure on the surface and the ability to release lenvatinib in a sustained manner. Lenvatinib-loaded nanoparticles were tested in vitro on HCC cells to evaluate their anticancer efficacy compared to free drug. Furthermore, the enhanced in vivo efficacy of lenvatinib-loaded nanoparticles on nude mice HCC xenograft models was demonstrated by evaluating tumor burdens, apoptotic markers and histological scores after administration of lenvatinib-nanoparticles via intraperitoneal or oral route. Finally, in vivo biodistribution studies were performed, demonstrating the ability of the prepared drug delivery systems to significantly accumulate in the solid tumor by active targeting, due to the presence of biotin on the nanoparticle surface.

Modulating the release of bioactive molecules of human mesenchymal stromal cell secretome: Heparinization of hyaluronic acid-based hydrogels.

An amine derivative of hyaluronic acid (HA) was crosslinked to obtain a 3D dried sponge. The sponge was subsequently rehydrated using secretome from human mesenchymal stromal cells (MSCs), resulting in the formation of a hydrogel. The release kinetics analysis demonstrated that the hydrogel effectively sustained secretome release, with 70% of the initially loaded wound-healing-associated cytokines being released over a 12-day period. Tuning the hydrogel properties through heparin crosslinking resulted in a biomaterial with a distinct mechanism of action. Specifically, the presence of heparin enhanced water uptake capacity of the hydrogel and increased its sensitivity to enzymatic degradation. Notably, the heparin crosslinking also led to a significant retention of cytokines within the hydrogel matrix. Overall, the secretome-rehydrated HA hydrogel holds promise as a versatile device for regenerative medicine applications: the non-heparinized hydrogel may function as a biomaterial with low reabsorption rates, sustaining the release of bioactive molecules contained in MSC secretome. In contrast, the heparinized hydrogel may serve as a depot of bioactive molecules with faster reabsorption rates. Given its patch-like characteristic, the HA-based hydrogel appears suitable as topical treatment for external organs, such as the skin.

Topical application of a hyaluronic acid-based hydrogel integrated with secretome of human mesenchymal stromal cells for diabetic ulcer repair.

This preclinical proof-of-concept study aimed to evaluate the effectiveness of secretome therapy in diabetic mice with pressure ulcers. We utilized a custom-made hyaluronic acid (HA)-based porous sponge, which was rehydrated either with normal culture medium or secretome derived from human mesenchymal stromal cells (MSCs) to achieve a hydrogel consistency. Following application onto skin ulcers, both the hydrogel-only and the hydrogel + secretome combination accelerated wound closure compared to the vehicle group. Notably, the presence of secretome significantly enhanced the healing effect of the hydrogel, as evidenced by a thicker epidermis and increased revascularization of the healed area compared to the vehicle group. Notably, molecular analysis of healed skin revealed significant downregulation of genes involved in delayed wound healing and abnormal inflammatory response in ulcers treated with the hydrogel + secretome combination, compared to those treated with the hydrogel only. Additionally, we found no significant differences in therapeutic outcomes when comparing the use of secretome from fetal dermal MSCs to that from umbilical cord MSCs. This observation is supported by the proteomic profile of the two secretomes, which suggests a shared molecular signature responsible of the observed therapeutic effects.

Schiff Base-Based Hydrogel Embedded with In Situ Generated Silver Nanoparticles Capped by a Hyaluronic Acid-Diethylenetriamine Derivative for Wound Healing Application.

In this study, hydrogels were produced using a Schiff base reaction between two hyaluronic acid derivatives: one containing aldehyde groups (HA-Ald) and the other holding a diethylenetriamine with terminal amino groups (HA-DETA). The DETA portion promotes the in situ growth, complexation, and stabilization of silver nanoparticles (AgNPs), eliminating the need for external reducing agents. The reaction between HA-DETA and HA-Ald leads to the formation of imine bonds, which results in dynamically pH-responsive cross-linking. While the DETA capping ability helped in embedding the AgNPs, the on/off pH environmental responsivity of the hydrogel allows for a controlled and on-demand release of the drug, mainly when bacterial infections cause pH variation of the wound bed. The injectable hydrogels resulted in being highly compatible in contact with blood red cells, fibroblasts, and keratinocytes and capable of having a proliferative effect on an in vitro wound scratch model. The pH-responsive hydrogels showed proper antibacterial activity againstPseudomonas aeruginosaandStaphylococcus aureus, common bacterial strains presented in wound infections. Finally, in vivo wound model studies demonstrated an overall speeding up in the wound healing rate and advanced wound conditions in the experimental group treated with the hydrogels compared to control samples.

Nanoaggregates based on new poly-hydroxyethyl-aspartamide copolymers for oral insulin absorption.

The aim of this work was to produce copolymers with an appropriate hydrophilic/hydrophobic balance able to form nanoaggregates with protein molecules and to be used as ideal materials in the field of oral peptide/protein delivery. New anionic polymers obtained by the conjugation of carboxy-bearing ligands, like succinic anhydride and/or cysteine, to hydrophobized α,ß-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) copolymers have been synthesized and characterized. Starting copolymer was synthesized by the partial derivatization of hydroxyl groups on the PHEA backbone with butylamine (C4) (obtaining the PHEA-C4 copolymer, bearing a butyl moiety). The consecutive reaction of PHEA-C4 with succinic anhydride permitted the PHEA-C4-S copolymer to be obtained, bearing pendant carboxylic groups as well. Finally, part of the pendant carboxylic groups were conjugated to cysteine via an amidic bond, obtaining PHEA-C4-S-Cyst. All synthesized copolymers, PHEA-C4, PHEA-C4-S, and PHEA-C4-S-Cyst, exhibit the ability to interact with insulin in aqueous medium forming nanoaggregates. Physical characterization of prepared insulin/copolymer nanoaggregates was carried out by means of turbidimetric measurements and DLS analysis. These studies demonstrated that synthesized copolymers form colloidal aggregates in the presence of insulin, with size ranging between 62 and 216 nm. Stability studies in the presence of the peptidase α-chymotrypsin showed also the ability of synthesized copolymers to increase insulin stability against enzymatic degradation in the order PHEA-C4-S-Cyst > PHEA-C4-S > PHEA-C4. Moreover, in dosage form such as tablets, the synthesized copolymers displayed the properties to prolong disintegration time and control release of the embedded peptide drug into media mimicking intestinal fluids. The administration of insulin in the presence of PHEA-C4-S-Cyst and PHEA-C4-S copolymers resulted in the ability to provoke a certain absorption of insulin and consequently to induce in vivo hypoglycemic effects on rats after oral administration with respect to free insulin. In particular, the hypoglycemic effect shown by PHEA-C4-S/insulin nanoaggregates was equal to almost 30% of the effect observed after the administration of insulin by conventional subcutaneous administration and about 20% in the case of PHEA-C4-S-Cyst/insulin nanoaggregates. These copolymers are good starting materials for the preparation of an oral dosage form of proteins.

Dexamethasone dipropionate loaded nanoparticles of α-elastin-g-PLGA for potential treatment of restenosis.

A graft copolymer of α-elastin with poly(lactic-co-glycolic) acid (PLGA) has been synthesized and successfully employed to produce nanoparticles. Exploiting the known biological activity of α-elastin to promote the maintenance of smooth muscle cells (SMCs) contractile phenotype and the antiproliferative effect of glucocorticoids, the aim of this research was to produce drug-loaded nanoparticles suitable for potential treatment of restenosis. In particular, nanoparticles of α-elastin-g-PLGA with a mean size of 200 nm have been produced and loaded with dexamethasone dipropionate (10% w/w), chosen as a model drug that inhibits proliferation of vascular SMCs. These nanoparticles are able to prolong the drug release and show a pronounced sensibility to elastase. Drug unloaded nanoparticles stimulate the differentiation of human umbilical artery smooth muscle cells (HUASMCs) toward the contractile phenotype as demonstrated by immunofluorescence, flow cytofluorimetric, and western blotting analyses. Finally, drug-loaded nanoparticles efficiently reduce viability of HUASMCs as evidenced by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2- (4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay.

Galactosylated micelles for a ribavirin prodrug targeting to hepatocytes.

Polymeric micelles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors, that is, ASGPR, were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,ß-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-dl-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, obtaining PHEA-EDA-PLA-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, that is, RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. Liver-targeted RBV tripalmitate-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometric size. By in vitro experiments, the specificity of RBV tripalmitate-loaded PHEA-EDA-PLA-GAL micelles toward HepG2 was demonstrated by using a competitive inhibition assay in the presence of free GAL. This finding raises hope in terms of future micelles-based liver-targeted drug delivery strategy for the hepatitis C treatment.

Antibacterial Broad-Spectrum Dendritic/Gellan Gum Hybrid Hydrogels with Rapid Shape-Forming and Self-Healing for Wound Healing Application.

Treating wound infections is a difficult task ever since pathogenic bacteria started to develop resistance to common antibiotics. The present study develops hybrid hydrogels based on the formation of a polyelectrolyte complex between the anionic charges of dopamine-functionalized Gellan Gum (GG-DA) and the cationic moieties of the TMP-G2-alanine dendrimer. The hydrogels thus obtained can be doubly crosslinked with CaCl2 , obtaining solid hydrogels. Or, by oxidizing dopamine to GG-DA, possibly causing further interactions such as Schiff Base and Michael addition to take place, hydrogels called injectables can be obtained. The latter have shear-thinning and self-healing properties (efficiency up to 100%). Human dermal fibroblasts (HDF), human epidermal keratinocytes (HaCaT), and mouse monocyte cells (RAW 264.7), after incubation with hydrogels, in most cases show cell viability up to 100%. Hydrogels exhibit adhesive behavior on various substrates, including porcine skin. At the same time, the dendrimer serves to crosslink the hydrogels and endows them with excellent broad-spectrum microbial eradication activity within four hours, evaluated using Staphylococcus aureus 2569 and Escherichia coli 178. Using the same GG-DA/TMP-G2-alanine ratios hybrid hydrogels with tunable properties and potential for wound dressing applications can be produced.

Near-infrared light-responsive and antibacterial injectable hydrogels with antioxidant activity based on a Dopamine-functionalized Gellan Gum for wound healing.

The development of wound dressings with combined antioxidant, antibacterial and tissue adhesion functions has been a difficult medical task for the treatment of wound infections. We synthetized a dopamine and PEG functionalized Gellan Gum (GG) to produce an injectable hydrogel with radical scavenging activity having both specific and aspecific antibiotic/antimicrobial properties. Using starting GG with different molecular weights, we obtained two derivatives that have been used to prepare the gel precursor dispersion, that undergoes gelation in the presence of colistin and dried microparticles (MPs) functionalized on the surface with polydopamine (pDA). Both were used to dope the hydrogel, increase the radical scavenger activity and impart near-infrared light (NIR) responsiveness. Indeed, with an irradiation of 810 nm, the incorporated microparticles exhibit photothermal transformation properties and improve the release of antibiotics on demand. The combination of photothermal and antibiotic therapy with synergistic antibacterial action acts on Pseudomonas aeruginosa and leads to a bactericidal effect in a few hours, while on Staphylococcus aureus there is an effect of inhibition of growth over time due only to the hyperthermic effect. We believe this study provides a promising method for fabricating a multifunctional injectable hydrogel for the potential treatment of infected skin wounds.

Development of stimulus-sensitive electrospun membranes based on novel biodegradable segmented polyurethane as triggered delivery system for doxorubicin.

In this work, redox-sensitive polyurethane urea (PUU) based electrospun membranes have been exploited to chemically tether a pH-sensitive doxorubicin derivative achieved by linking a lipoyl hydrazide to the drug via a hydrazone linkage. First, the lipoyl-hydrazone-doxorubicin derivative labelled as LA-Hy-Doxo has been synthesized and characterized. Then, the molecule has been tethered, via a thiol-disulfide exchange reaction, to the redox-sensitive PUU (PolyCEGS) electrospun membrane. The redox-sensitive PolyCEGS PUU has been produced by using PCL-PEG-PCL polyol and glutathione-tetramethyl ester (GSSG-OMe)4 as a chain extender. The LA-Hy-Doxo tethered electrospun membrane has showed a dually controlled release triggered by acidic and reducing conditions, producing a significant cytotoxic effect in human breast cancer cell lines (MCF-7) which has validated the system for the post-surgical treatment of solid tumors to contrast recurrence.

Photothermal nanofibrillar membrane based on hyaluronic acid and graphene oxide to treat Staphylococcus aureus and Pseudomonas aeruginosa infected wounds.

Here we reported the fabrication of an electrospun membrane based on a hyaluronic acid derivative (HA-EDA) to be used as a bandage for the potential treatment of chronic wounds. The membrane, loaded with graphene oxide (GO) and ciprofloxacin, showed photothermal properties and light-triggered drug release when irradiated with a near-infrared (NIR) laser beam. Free amino groups of HA-EDA derivative allowed autocrosslinking of the electrospun membrane; thus, a substantial enhancement in the hydrolytic resistance of the patch was obtained. In vitro antibacterial activity studies performed on Staphylococcus aureus and Pseudomonas aeruginosa revealed that such electrospun membranes, due to the synergistic effect of the antibiotic and NIR-mediated hyperthermia, reduced the viability of both pathogens. Specific in vitro experiment demonstrated also that is possible to disrupt, through laser irradiation, the biofilms formed onto the membrane.

Correlating Rheological Properties of a Gellan Gum-Based Bioink: A Study of the Impact of Cell Density.

Here, for the production of a bioink-based gellan gum, an amino derivative of this polysaccharide was mixed with a mono-functionalized aldehyde polyethyleneglycol in order to improve viscoelastic macroscopic properties and the potential processability by means of bioprinting techniques as confirmed by the printing tests. The dynamic Schiff base linkage between amino and aldehyde groups temporally modulates the rheological properties and allows a reduction of the applied pressure during extrusion followed by the recovery of gellan gum strength. Rheological properties, often related to printing resolution, were extensively investigated confirming pseudoplastic behavior and thermotropic and ionotropic responses. The success of bioprinting is related to different parameters. Among them, cell density must be carefully selected, and in order to quantify their role on printability, murine preostoblastic cells (MC3T3-E1) and human colon tumor cells (HCT-116) were chosen as cell line models. Here, we investigated the effect of their density on the bioink's rheological properties, showing a more significant difference between cell densities for MC3T3-E1 compared to HCT-116. The results suggest the necessity of not neglecting this aspect and carrying out preliminary studies to choose the best cell densities to have the maximum viability and consequently to set the printing parameters.

Composite Hydrogels of Alkyl Functionalized Gellan Gum Derivative and Hydroxyapatite/Tricalcium Phosphate Nanoparticles as Injectable Scaffolds for bone Regeneration.

An alkyl functionalized gellan gum derivative is here used to produce hydrogels containing hydroxyapatite and tricalcium phosphate nanoparticles as injectable nanostructured scaffolds for bone regeneration. The amphiphilic nature of the polysaccharide derivative along with its thermotropic behavior and ionotropic crosslinking features make possible to produce injectable bone mimetic scaffolds that can be used to release viable cells and osteoinductive biomolecules. The influence of different nanoparticles concentration on the rheological and physicochemical properties of the injectable systems is studied. It is found that the presence of inorganic nanoparticles reinforces the 3D hydrated polymeric networks without influencing their injectability but improving the physicochemical properties of ionotropic crosslinked hydrogels produced with two different curing media. Preliminary cytocompatibility tests performed with murine preosteoblast cells revealed that gellan gum based hydrogels can safely encapsulate viable cells. Loading and release experiments for dexamethasone and stromal cell-derived factor-1 demonstrate the drug delivery features of the obtained injectable systems.

Galactosylated Polymer/Gold Nanorods Nanocomposites for Sustained and Pulsed Chemo-Photothermal Treatments of Hepatocarcinoma.

In this paper, we propose a rational design of a hybrid nanosystem capable of locally delivering a high amount of hydrophobic anticancer drugs (sorafenib or lenvatinib) and heat (hyperthermia) in a remote-controlled manner. We combined in a unique nanosystem the excellent NIR photothermal conversion of gold nanorods (AuNRs) with the ability of a specially designed galactosylated amphiphilic graft copolymer (PHEA-g-BIB-pButMA-g-PEG-GAL) able to recognize hepatic cells overexpressing the asialoglycoprotein receptor (ASGPR) on their membranes, thus giving rise to a smart composite nanosystem for the NIR-triggered chemo-phototherapy of hepatocarcinoma. In order to allow the internalization of AuNRs in the hydrophobic core of polymeric nanoparticles, AuNRs were coated with a thiolated fatty acid (12-mercaptododecanoic acid). The drug-loaded hybrid nanoparticles were prepared by the nanoprecipitation method, obtaining nanoparticles of about 200 nm and drug loadings of 9.0 and 5.4% w/w for sorafenib and lenvatinib, respectively. These multifunctional nanosystems have shown to convert NIR radiation into heat and release charged drugs in a remote-controlled manner. Then, the biocompatibility and synergistic effects of a chemo-phototherapy combination, as well the receptor-mediated internalization, were evaluated by an in vitro test on HepG2, HuH7, and NHDF. The results indicate that the proposed nanoparticles can be considered to be virtuous candidates for an efficient and selective dual-mode therapy of hepatocarcinoma.

Fabrication of silver nanoparticles by a diethylene triamine-hyaluronic acid derivative and use as antibacterial coating.

In this work a synthetic protocol for the functionalization of hyaluronic acid with diethylenetriamine (DETA) was standardized. HA-DETA derivatives were characterized by NMR and proton carbon correlation analysis HSQC and HMBC to confirm chemical structure. A selected derivative was used to set up a green fabrication procedure for HA-DETA capped silver nanoparticles with the aim to achieve a polymeric based coating with potential application in the treatment of medical devices associated infections. Data from UV-visible spectroscopy, electron scanning and transmission microscope (STEM), photoelectric spectroscopy (XPS) and rheological characterization were combined to characterize the HA-DETA/Ag nanocomposites. HA-DETA stabilized Ag nanoparticles (10-30 nm) were obtained through an UV accelerated production. The viability of MC3T3-E1 was analyzed with the aim of designing a cytocompatible antimicrobial coating. Antibacterial and antibiofilm activity of HA-DETA/Ag nanocomposites have been tested in vitro against Staphylococcus aureus and Pseudomonas aeruginosa both in culture plates than on titanium specimens.