In late stages of inherited and acquired retinal diseases such as Stargardt disease (STGD) or dry age-related macular degeneration (AMD), loss of retinal pigment epithelia (RPE) cells and subsequently photoreceptors in the macular area result in a dramatic decline of central visual function. Repopulating this area with functional RPE cells may prevent or decline the progression of photoreceptor loss. In the present study, the viability, survival, and integration of human induced pluripotent stem cell (hiPSC)-derived RPE cells (hiPSC-RPE) is assessed generated using clinical-grade protocol and cultured on a clinically relevant scaffold (poly-L-lactide-co-D, L-lactide, PDLLA) after subretinal implantation in immunosuppressed minipigs for up to 6 weeks. It is shown that transplanted hiPSC-RPE cells maintain the RPE cell features such as cell polarity, hexagonal shape, and cell-cell contacts, and interact closely with photoreceptor outer segments without signs of gliosis or neuroinflammation throughout the entire period of examination. In addition, an efficient immunosuppressing strategy with a continuous supply of tacrolimus is applied. Continuous verification and improvement of existing protocols are crucial for its translation to the clinic. The results support the use of hiPSC-RPE on PDLLA scaffold as a cell replacement therapeutic approach for RPE degenerative diseases.

• Klíčová slova
• Human induced pluripotent stem cells;minipigs, age‐related macular degeneration, cell therapy, retina, retinal degeneration, retinal pigment epithelium,
• MeSH
• fotoreceptory * MeSH
• indukované pluripotentní kmenové buňky * cytologie   transplantace   MeSH
• lidé MeSH
• makulární degenerace terapie   MeSH
• miniaturní prasata MeSH
• prasata MeSH
• retina * cytologie   MeSH
• retinální pigmentový epitel * cytologie   transplantace   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The use of electrospun polymeric biodegradable materials for medical applications is becoming increasingly widespread. One of the most important parameters regarding the functionality of nanofiber scaffolds during implantation and the subsequent regeneration of damaged tissues concerns their stability and degradation behavior, both of which are influenced by a wide range of factors (the properties of the polymer and the polymer solution, the technological processing approach, the sterilization method, etc.). This study monitored the degradation of nanofibrous materials fabricated from degradable polyesters as a result of the sterilization method applied (ethylene oxide and gamma irradiation) and the solvent system used to prepare the spun polymer solution. Aliphatic polyesters PCL and PLCL were chosen for this study and selected with respect to the applicability and handling in the surgical setting of these nanofibrous materials for vascular bandaging. The results revealed that the choice of solvent system exerts a significant impact on degradation during sterilization, especially at higher gamma irradiation values. The subsequent enzyme-catalyzed degradation of the materials following sterilization indicated that the choice of the sterilization method influenced the degradation behavior of the materials. Whereas wave-like degradation was evident concerning ethylene oxide sterilization, no such behavior was observed following gamma-irradiation sterilization. With concern for some of the tested materials, the results also indicated the potential for influencing the development of degradation within the bulk versus degradation from the surface of the material. Both the sterilization method and the choice of the spinning solvent system were found to impact degradation, which was observed to be most accelerated in the case of PLCL (L-lactide-co-caprolactone copolymer) electrospun from organic acids and subsequently sterilized using gamma irradiation. Since we planned to use these materials in cardiovascular applications, it was decided that their hemocompatibility would also be tested. The results of these tests revealed that changes in the structures of the materials initiated by sterilization may exert thrombogenic and anticoagulant impacts. Moreover, the microscopic analysis suggested that the solvent system used in the preparation of the materials potentially affects the behavior of erythrocytes; however, no indication of the occurrence of hemolysis was detected.

• Klíčová slova
• biodegradable polyester, electrospun nanofibers, enzymatically catalyzed degradation, ethylene oxide, gamma irradiation, hemocompatibility, sterilization,
• Publikační typ
• časopisecké články MeSH

Active wound dressings are attracting extensive attention in soft tissue repair and regeneration, including bacteria-infected skin wound healing. As the wide use of antibiotics leads to drug resistance we present here a new concept of wound dressings based on the polycaprolactone nanofiber scaffold (NANO) releasing second generation lipophosphonoxin (LPPO) as antibacterial agent. Firstly, we demonstrated in vitro that LPPO released from NANO exerted antibacterial activity while not impairing proliferation/differentiation of fibroblasts and keratinocytes. Secondly, using a mouse model we showed that NANO loaded with LPPO significantly reduced the Staphylococcus aureus counts in infected wounds as evaluated 7 days post-surgery. Furthermore, the rate of degradation and subsequent LPPO release in infected wounds was also facilitated by lytic enzymes secreted by inoculated bacteria. Finally, LPPO displayed negligible to no systemic absorption. In conclusion, the composite antibacterial NANO-LPPO-based dressing reduces the bacterial load and promotes skin repair, with the potential to treat wounds in clinical settings.

• MeSH
• antibakteriální látky aplikace a dávkování   terapeutické užití   MeSH
• hojení ran účinky léků   MeSH
• infekce v ráně farmakoterapie   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• nanovlákna * MeSH
• obvazy * MeSH
• stafylokokové infekce farmakoterapie   MeSH
• Staphylococcus aureus * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH

Polycaprolactone composite nanofibers coated with a polydopamine layer are introduced as a new type of absorption material for on-line solid phase extraction (SPE) in chromatographic system. A hybrid technology combining the electrospinning and melt blowing was used for the preparation of 3D-structured microfiber/nanofibrous polycaprolactone composite. The dopamine coating was then applied to functionalize the micro/nanofibers. Polydopamine-coated polycaprolactone fibers were tested as an extraction phase in on-line SPE prior to HPLC separation and UV detection. Four groups of biologically active substances including bisphenols (Bisphenol S, Bisphenol AF, Bisphenol A, Bisphenol C, Bisphenol AP, Bisphenol Z, Bisphenol BP, and Bisphenol M), betablockers (Timolol, Metoprolol, Labetalol, and Propranolol), nonsteroidal antiphlogistic drugs (Salicylic acid, Ketoprofen, Naproxen, Indomethacin, Diclofenac, Ibuprophen, and Meclofenamic acid), and phenolic acids (Chlorogenic acid, Caffeic acid, Sinapic acid, m-Coumaric acid, Benzoic acid, and Cinnamic acid) were used as the model analytes. Neat and coated fibers were compared and applied as sorbents for the on-line extraction set-up. Both materials produced good extraction potential for the determination of bisphenols and nonsteroidal drugs in model biological and environmental samples including river water, human urine, and blood serum. However, the polydopamine layer significantly increased the extraction efficiency of polar drugs. Typical repeatability of on-line extraction procedure on polydopamine coated fibers was in the range 0.12-4.11% for bisphenols, 0.55-1.41% for antiphlogistic drugs, 0.59-2.52% for phenolic acids, and 1.01-1.65% for betablockers. Graphical abstract Schematic representation of polycaprolactone composite nanofibers coated with a polydopamine layer as an advanced absorption material for on-line solid phase extraction in chromatography.

• Klíčová slova
• Chromatography, Column switching, Degradation, Dopamine coating, Micro-column, Microfiber, Nanofiber, Polymerization, Solid phase extraction, Surface modification,
• MeSH
• antiflogistika nesteroidní analýza   izolace a purifikace   MeSH
• beta blokátory analýza   izolace a purifikace   MeSH
• chemické látky znečišťující vodu analýza   izolace a purifikace   MeSH
• cinnamáty analýza   izolace a purifikace   MeSH
• extrakce na pevné fázi metody   MeSH
• fenoly analýza   izolace a purifikace   MeSH
• indoly chemie   MeSH
• nanovlákna chemie   MeSH
• polyestery chemie   MeSH
• polymerizace MeSH
• polymery chemie   MeSH
• řeky chemie   MeSH
• reprodukovatelnost výsledků MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• beta blokátory MeSH
• chemické látky znečišťující vodu MeSH
• cinnamáty MeSH
• fenoly MeSH
• indoly MeSH
• polycaprolactone MeSH Prohlížeč
• polydopamine MeSH Prohlížeč
• polyestery MeSH
• polymery MeSH