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Cold atmospheric plasma (CAP) is an ionized matter with potential applications in various medical fields, ranging from wound healing and disinfection to cancer treatment. CAP's clinical usefulness stems from its ability to act as an adjustable source of reactive oxygen and nitrogen species (RONS), which are known to function as pleiotropic signaling agents within cells. Plasma-activated species, such as RONS, have the potential to be consistently and precisely released by carriers, enabling their utilization in a wide array of biomedical applications. Furthermore, understanding the behavior of CAP in different environments, including water, salt solutions, culture medium, hydrogels, and nanoparticles, may lead to new opportunities for maximizing its therapeutic potential. This review article sought to provide a comprehensive and critical analysis of current biomaterial approaches for the targeted delivery of plasma-activated species in the hope to boost therapeutic response and clinical applicability.

Biomaterials and coating techniques unlock major benefits for advanced medical therapies. Here, we explored layer-by-layer (LbL) deposition of silk fibroin (SF) by dip coating to deploy homogeneous films on different materials (titanium, magnesium, and polymers) frequently used for orthopedic and other bone-related implants. Titanium and magnesium specimens underwent preceding plasma electrolytic oxidation (PEO) to increase hydrophilicity. This was determined as surface properties were visualized by scanning electron microscopy and contact angle measurements as well as Fourier transform infrared spectroscopy (FTIR) analysis. Finally, biological in vitro evaluations of hemocompatibility, THP-1 cell culture, and TNF-α assays were conducted. A more hydrophilic surface could be achieved using the PEO surface, and the contact angle for magnesium and titanium showed a reduction from 73 to 18° and from 58 to 17°, respectively. Coating with SF proved successful on all three surfaces, and coating thicknesses of up to 5.14 μm (±SD 0.22 μm) were achieved. Using FTIR analysis, it was shown that the insolubility of the material was achieved by post-treatment with water vapor annealing, although the random coil peak (1640–1649 cm–1) and the α-helix peak (at 1650 cm–1) were still evident. SF did not change hemocompatibility, regardless of the substrate, whereas the PEO-coated materials showed improved hemocompatibility. THP-1 cell culture showed that cells adhered excellently to all of the tested material surfaces. Interestingly, SF coatings induced a significantly higher amount of TNF-α for all materials, indicating an inflammatory response, which plays an important role in a variety of physiological processes, including osteogenesis. LbL coatings of SF are shown to be promising candidates to modulate the body’s immune response to implants manufactured from titanium, magnesium, and polymers. They may therefore facilitate future applications for bioactive implant coatings. However, further in vivo studies are needed to confirm the proposed effects on osteogenesis in a physiological environment.

Oral wounds are among the most troublesome injuries which easily affect the patients' quality of life. To date, the development of functional antibacterial dressings for oral wound healing remains a challenge. In this regard, we investigated antibacterial silk protein-based membranes for the application as wound dressings in oral and maxillofacial surgery. The present study includes five variants of casted membranes, i.e., i) membranes-silver nanoparticles (CM-Ag), ii) membranes-gentamicin (CM-G), iii) membranes-control (without functionalization) (CM-C), iv) membranes-silk sericin control (CM-SSC), and v) membranes-silk fibroin/silk sericin (CM-SF/SS), and three variants of nonwovens, i.e., i) silver nanoparticles (NW-Ag), ii) gentamicin (NW-G), iii) control (without functionalization) (NW-C). The surface structure of the samples was visualized with scanning electron microscopy. In addition, antibacterial testing was accomplished using agar diffusion assay, colony forming unit (CFU) analysis, and qrt-PCR. Following antibacterial assays, biocompatibility was evaluated by cell proliferation assay (XTT), cytotoxicity assay (LDH), and live-dead assay on L929 mouse fibroblasts. Findings indicated significantly lower bacterial colony growth and DNA counts for CM-Ag with a reduction of bacterial counts by 3log levels (99.9% reduction) in CFU and qrt-PCR assay compared to untreated control membranes (CM-C and CM-SSC) and membranes functionalized with gentamicin (CM-G and NW-G) (p < 0.001). Similarly, NW-G yielded significantly lower DNA and colony growth counts compared to NW-Ag and NW-C (p < 0.001). In conclusion, CM-Ag represented 1log level better antibacterial activity compared to NW-G, whereas NW-G showed better cytocompatibility for L929 cells. As data suggest, these two membranes have the potential of application in the field of bacteria-free oral wound healing. However, provided that loading strategy and cytocompatibility are adjusted according to the antibacterial agents' characteristic and fabrication technique of the membranes.

Codeine is a common drug widely used in some countries as a pain reliever. The effect of codeine on yeast sucrase activity was studied in this report. Non-competitive inhibition was observed using double reciprocal plot. The Km of enzyme did not change in the presence of different concentrations of codeine (0.5- 1.5 mM) and was determined about 11.5 mM. The Vmax of enzyme was determined about 8.8 mM/min, and the Vmax decreased in the presence of codeine. The Ki of codeine was measured by using the reaction rate and the initial concentration of the inhibitor according to the Dixon plot. The Ki was found to be 0.42 mM and the IC50 of codeine was determined about 0.875 mM.

PTEN hamartoma tumour syndrome (PHTS) is a heterogeneous group of rare, autosomal dominant disorders associated with PTEN germline mutations. PHTS patients routinely develop hamartomas, which are benign tissue overgrowths comprised of disorganized ‘normal’ cells. Efforts to generate PHTS animal models have been largely unsuccessful due to the early lethality of homozygous germline mutations in Pten, together with the lack of hamartoma formation in most conditional mutants generated to date. We report herein a novel PHTS mouse model that reproducibly forms hamartoma-like lesions in the central retina by postnatal day 21. Specifically, we generated a Pten conditional knockout (cKO) using a retinal-specific Pax6::Cre driver that leads to a nearly complete deletion of Pten in the peripheral retina but produces a mosaic of ‘wild-type’ and Pten cKO cells centrally. Structural defects were only observed in the mosaic central retina, including in Müller glia and in the outer and inner limiting membranes, suggesting that defective mechanical integrity partly underlies the hamartoma-like pathology. Finally, we used this newly developed model to test whether rapamycin, an mTOR inhibitor that is currently the only PHTS therapy, can block hamartoma growth. When administered in the early postnatal period, prior to hamartoma formation, rapamycin reduces hamartoma size, but also induces new morphological abnormalities in the Pten cKO retinal periphery. In contrast, administration of rapamycin after hamartoma initiation fails to reduce lesion size. We have thus generated and used an animal model of retinal PHTS to show that, although current therapies can reduce hamartoma formation, they might also induce new retinal dysmorphologies. This article has an associated First Person interview with the first author of the paper.