No abstract

Layer-by-layer (LbL) polyelectrolyte coatings are intensively studied as reservoirs of bioactive proteins for modulating interactions between biomaterial surfaces and cells. Mild conditions for the incorporation of growth factors into delivery systems are required to maintain protein bioactivity. Here, we present LbL films composed of water-soluble N- [(2-hydroxy-3trimethylammonium)propyl] chitosan chloride (HTCC), heparin (Hep), and tannic acid (TA) fabricated under physiological conditions with the ability to release heparin-binding proteins. Surface plasmon resonance analysis showed that the films formed on an anchoring HTCC/TA bilayer, with TA serving as a physical crosslinker, were more stable during their assembly, leading to increased film thickness and increased protein release. X-ray reflectivity measurements confirmed intermixing of the deposited layers. Protein release also increased when the proteins were present as an integral part of the Hep layers rather than as individual protein layers. The 4-week release pattern depended on the protein type; VEGF, CXCL12, and TGF-β1 exhibited a typical high initial release, whereas FGF-2 was sustainably released over 4 weeks. Notably, the films were nontoxic, and the released proteins retained their bioactivity, as demonstrated by the intensive chemotaxis of T-lymphocytes in response to the released CXCL12. Therefore, the proposed LbL films are promising biomaterial coating candidates for stimulating cellular responses.

Aqueous solutions of some polymers exhibit a lower critical solution temperature (LCST); that is, they form phase‐separated aggregates when heated above a threshold temperature. Such polymers found many promising (bio)medical applications, including in situ thermogelling with controlled drug release, polymer‐supported radiotherapy (brachytherapy), immunotherapy, and wound dressing, among others. Yet, despite the extensive research on medicinal applications of thermoresponsive polymers, their biodistribution and fate after administration remained unknown. Thus, herein, they studied the pharmacokinetics of four different thermoresponsive polyacrylamides after intramuscular administration in mice. In vivo, these thermoresponsive polymers formed depots that subsequently dissolved with a two‐phase kinetics (depot maturation, slow redissolution) with half‐lives 2 weeks to 5 months, as depot vitrification prolonged their half‐lives. Additionally, the decrease of TCP of a polymer solution increased the density of the intramuscular depot. Moreover, they detected secondary polymer depots in the kidneys and liver; these secondary depots also followed two‐phase kinetics (depot maturation and slow dissolution), with half‐lives 8 to 38 days (kidneys) and 15 to 22 days (liver). Overall, these findings may be used to tailor the properties of thermoresponsive polymers to meet the demands of their medicinal applications. Their methods may become a benchmark for future studies of polymer biodistribution.

Two photoactivatable dicarbonyl ruthenium(II) complexes based on an amide‐functionalised bipyridine scaffold (4‐position) equipped with an alkyne functionality or a green‐fluorescent BODIPY (boron‐dipyrromethene) dye have been prepared and used to investigate their light‐induced decarbonylation. UV/Vis, FTIR and 13C NMR spectroscopies as well as gas chromatography and multivariate curve resolution alternating least‐squares analysis (MCR‐ALS) were used to elucidate the mechanism of the decarbonylation process. Release of the first CO molecule occurs very quickly, while release of the second CO molecule proceeds more slowly. In vitro studies using two cell lines A431 (human squamous carcinoma) and HEK293 (human embryonic kidney cells) have been carried out in order to characterise the anti‐proliferative and anti‐apoptotic activities. The BODIPY‐labelled compound allows for monitoring the cellular uptake, showing fast internalisation kinetics and accumulation at the endoplasmic reticulum and mitochondria.

of patients in need of such surgery, which can significantly improve one's quality of life. [1] Unfortunately, orthopedic implants are highly susceptible to peri-implant sterile inflammation or microbial infections (prosthetic joint infections, PJI). These complications, which manifest as pain, erythema, swelling and discharge from the wound site, require long hospitalizations and can lead to osteomyelitis, implant failure, sepsis, multiorgan dysfunction, amputation or even death. [2,3] PJI occur in 1-2% of primary arthroplasty surgeries and up to 4% of revision arthroplasty surgeries. [4] Traditionally, PJI are classified as early (<3 months after surgery), delayed (3-24 months after surgery), or late (>2 years after surgery). [5] The sources of bacterial infection might be the operating room and surgical equipment, bacteria from the patient's skin, and bacteria that already reside in the patient's body. Early and acute infections are usually preceded by a systemic infection such as sepsis or soft-tissue infection. [6] The origins of chronic infections are either exogenous or hematogenous. [7] Implant-associated infections are the result of bacterial adhesion to an implant surface and subsequent formation of biofilm at the implantation site. [8][9][10] According to the surveillance European Centre for Disease Prevention and Control report from 2017, the The local peri-implant pH changes caused by sterile inflammation and bacterial and fungal infections are studied herein. Then, a sensing electrode based on polyaniline and poly(2-methyl-2-oxazoline) on a titanium alloy support is developed for potentiometric detection of peri-implant pH changes to enable early detection of the aforementioned pathologies. The infected endoprosthesis area is shown to have an average pH of 0.79 units lower than the aseptic sample. The pH measurements of the individual pathogenic bacteria or pathogenic yeast reveal that Escherichia coli decreased the pH by 1.24 units, Staphylococcus aureus decreased the pH by 1.33 units and the methicillin-resistant Staphylococcus aureus bacteria decreased the pH from 7.2 to 5.6 during 10 h, followed by a subsequent increase to 6.4. The results are statistically significant (α = 0.01). Pseudomonas aeruginosa is not shown to change pH levels. On the other hand, the pathogenic yeast has the lowest recorded pH, which decreases from 5.8 to 4.8. This difference in pH can be used to identify the nature of the infection. The developed electrodes have a pH response between pH 5 and 8, with a Nernstian slope of −59.6/pH. The developed electrode can contribute to the next generation of biosensors.