Direct-Write Deposition of Thermogels

The use of biocompatible hydrogels has widely extended the potential of additive manufacturing (AM) in the biomedical field leading to the production of 3D tissue and organ analogs for in vitro and in vivo studies. In this work, the direct-write deposition of thermosensitive hydrogels is described as a facile route to obtain 3D cell-laden constructs with controlled 3D structure and stable behavior under physiological conditions

Wound dressing products: A translational investigation from the bench to the market

Chronic skin wounds affect more than 40 million patients globally and represent a severe growing burden for the healthcare systems, with annual costs expected to exceed $15 billions by 2022. To satisfy the huge demand for effective wound care products, different types of wound dressings have been introduced on the market during the last decades. Based on “the moist wound healing theory” postulated by Prof Winter in 1962, bandages were initially designed to recreate the optimal wound environment to favor the healing process. Then, thanks to the advancements achieved in biomaterial design and processing, biotechnology, imaging and electronic fields, great effort has been devoted to the development of formulations able to actively participate to tissue healing. Indeed, both the literature and the market report the design of medicated wound dressings, i.e., wound care products releasing anti-microbial agents, anti-inflammatory drugs, or bioactive molecules. In this scenario, this review aims at critically describing the currently available wound care products, highlighting their proved effectiveness in wound management. Moreover, an overview of the main strategies exploited to design personalized wound dressings has been reported. Lastly, concerns on regulatory affairs and practical issues limiting the clinical translation of advanced research platforms have also been discussed

MicroRNA delivery through nanoparticles

MicroRNAs (miRNAs) are attracting a growing interest in the scientific community due to their central role in the etiology of major diseases. On the other hand, nanoparticle carriers offer unprecedented opportunities for cell specific controlled delivery of miRNAs for therapeutic purposes. This review critically discusses the use of nanoparticles for the delivery of miRNA-based therapeutics in the treatment of cancer and neurodegenerative disorders and for tissue regeneration. A fresh perspective is presented on the design and characterization of nanocarriers to accelerate translation from basic research to clinical application of miRNA-nanoparticles. Main challenges in the engineering of miRNA-loaded nanoparticles are discussed, and key application examples are highlighted to underline their therapeutic potential for effective and personalized medicine

Influence of Drug-Carrier Polymers on Alpha-Synucleinopathies: A Neglected Aspect in New Therapies Development.

Current therapeutic strategies to treat neurodegenerative diseases, such as alpha-synucleinopathies, aim at enhancing the amount of drug reaching the brain. Methods proposed, such as intranasal administration, should be able to bypass the blood brain barrier (BBB) and even when directly intracerebrally injected they could require a carrier to enhance local release of drugs. We have investigated the effect of a model synthetic hydrogel to be used as drug carrier on the amount of alpha-synuclein aggregates in cells in culture. The results indicated that alpha-synuclein aggregation was affected by the synthetic polymer, suggesting the need for testing the effect of any used material on the pathological process before its application as drug carrier.Peer Reviewe

In situ Forming Hyperbranched PEG—Thiolated Hyaluronic Acid Hydrogels With Honey-Mimetic Antibacterial Properties

The rapidly increasing resistance of bacteria to currently approved antibiotic drugs makes surgical interventions and the treatment of bacterial infections increasingly difficult. In recent years, complementary strategies to classical antibiotic therapy have, therefore, gained importance. One of these strategies is the use of medicinal honey in the treatment of bacterially colonized wounds. One of the several bactericidal effects of honey is based on the in situ generation of hydrogen peroxide through the activity of the enzyme glucose oxidase. The strategy underlying this work is to mimic this antibacterial redox effect of honey in an injectable, biocompatible, and rapidly forming hydrogel. The hydrogel was obtained by thiol–ene click reaction between hyperbranched polyethylene glycol diacrylate (HB PEGDA), synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization, and thiolated hyaluronic acid (HA-SH). After mixing 500 µL HB PEGDA (10%, w/w) and 500 µL HA-SH (1%, w/w) solutions, hydrogels formed in ∼60 s (HB PEGDA/HA-SH 10.0–1.0), as assessed by the tube inverting test. The HB PEGDA/HA-SH 10.0–1.0 hydrogel (200 µL) was resistant to in vitro dissolution in water for at least 64 days, absorbing up to 130 wt% of water. Varying glucose oxidase (GO) amounts (0–500 U/L) and constant glucose content (2.5 wt%) were loaded into HB PEGDA and HA-SH solutions, respectively, before hydrogel formation. Then, the release of H2O2 was evaluated through a colorimetric pertitanic acid assay. The GO content of 250 U/L was selected, allowing the formation of 10.8 ± 1.4 mmol H2O2/L hydrogel in 24 h, under static conditions. The cytocompatibility of HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with different GO activities (≤ 500 U/L) at a constant glucose amount (2.5 wt%) was investigated by in vitro assays at 24 h with L929 and HaCaT cell lines, according to DIN EN ISO 10993-5. The tests showed cytocompatibility for GO enzyme activity up to 250 U/L for both cell lines. The antibacterial activity of HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with increasing amounts of GO was demonstrated against various gram-positive bacteria (S. aureus and S. epidermidis), antibiotic-resistant gram-positive bacteria (MRSA and MRSE), gram-negative bacteria (P. aeruginosa, E. coli, and A. baumanii), and antibiotic-resistant gram-negative strains (P. aeruginosa and E. coli) using agar diffusion tests. For all gram-positive bacterial strains, increasing efficacy was measured with increasing GO activity. For the two P. aeruginosa strains, efficacy was shown only from an enzyme activity of 125 U/L and for E. coli and A. baumanii, efficacy was shown only from 250 U/L enzyme activity. HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with ≤250 U/L GO and 2.5 wt% glucose are promising formulations due to their fast-forming properties, cytocompatibility, and ability to produce antibacterial H2O2, warranting future investigations for bacterial infection treatment, such as wound care

Medical-grade silicone coated with rhamnolipid R89 is effective against Staphylococcus spp. Biofilms

Staphylococcus aureus and Staphylococcus epidermidis are considered two of the most important pathogens, and their biofilms frequently cause device-associated infections. Microbial biosurfactants recently emerged as a new generation of anti-adhesive and anti-biofilm agents for coating implantable devices to preserve biocompatibility. In this study, R89 biosurfactant (R89BS) was evaluated as an anti-biofilm coating on medical-grade silicone. R89BS is composed of homologues of the mono- (75%) and di-rhamnolipid (25%) families, as evidenced by mass spectrometry analysis. The antimicrobial activity against Staphylococcus spp. planktonic and sessile cells was evaluated by microdilution and metabolic activity assays. R89BS inhibited S. aureus and S. epidermidis growth with minimal inhibitory concentrations (MIC99) of 0.06 and 0.12 mg/mL, respectively and dispersed their pre-formed biofilms up to 93%. Silicone elastomeric discs (SEDs) coated by R89BS simple adsorption significantly counteracted Staphylococcus spp. biofilm formation, in terms of both built-up biomass (up to 60% inhibition at 72 h) and cell metabolic activity (up to 68% inhibition at 72 h). SEM analysis revealed significant inhibition of the amount of biofilm-covered surface. No cytotoxic effect on eukaryotic cells was detected at concentrations up to 0.2 mg/mL. R89BS-coated SEDs satisfy biocompatibility requirements for leaching products. Results indicate that rhamnolipid coatings are effective anti-biofilm treatments and represent a promising strategy for the prevention of infection associated with implantable devices