Kýla v jizvě patří k nejčastějším pooperačním komplikacím postihujících zhruba 20% všech pacientů po operaci břicha. Zhruba polovina pacientů po plastice kýly v jizvě recidivuje do 5 let, při případě použití kýlní síťky zhruba čtvrtina. Bohužel i kýlní síťka je zatížena řadou nežádoucích vedlejších účinků s celoživotním rizikem. Určitou změnu přinesl koncept biologických kýlních sítěk. Díky svému původu však vedou k imunologické odpovědi organismu a jejich příprava je velmi ekonomicky nákladná. Alternativou biologických materiálů by se mohla stát biokompatibilní nanovlákna polykaprolaktonu, které svou strukturou napodobují extracelulární matrix, což výrazně zlepšuje biokompatibilitu materiálu a vede k urychlení regenerace tkáně. V experimentech již byla ověřena jako materiál využitelný pro regeneraci břišní stěny. Nanovlákna budou dále funkcionalizována trombocytárními deriváty, jako zdroj růstových faktorů pro urychlení hojení tkání. Nosiče budou testovány in vitro a in vivo na malém zvířecím modelu (králik).; The incisional hernia is one of the most frequent complications affecting around 20% of all laparotomies. Around half of them suffer a recurrence when operated and one forth when surgical mesh is used. Unfortunately, even the surgical mesh can cause a wide range of complications and poses a lifelong risk for the patient. The biological mesh has brought a certain change to this concept. However, due to its biological origin this material triggers an immunological response of the organism and its manufacturing is extremely expensive. The biodegradable polycaprolactone nanofibres mimicking the extracellular matrix with their 3D structure could become an alternative as they are biocompatible and support fibroplasia. They have been tested as a material suitable for abdominal wall reconstruction already. Nanofibres will be further functionalized with platelet derivatives as a source of natural growth factors. Final samples will be tested on small animal model (rabbit).

• MeSH
• abdominální hernie komplikace   MeSH
• biokompatibilní materiály terapeutické užití   MeSH
• hojení ran MeSH
• incizní kýla prevence a kontrola   MeSH
• králíci MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• nanovlákna terapeutické užití   MeSH
• testování materiálů MeSH
• trombocyty MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• hodnotící studie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• preventivní medicína
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

Natural cosmetic products have recently re-emerged as a novel tool able to counteract skin aging and skin related damages. In addition, recently achieved progress in nanomedicine opens a novel approach yielding from combination of modern nanotechnology with traditional treatment for innovative pharmacotherapeutics. In the present study, we investigated the antiaging effect of a pretreatment with Myrtus communis natural extract combined with a polycaprolactone nanofibrous scaffold (NanoPCL-M) on skin cell populations exposed to UV. We set up a novel model of skin on a bioreactor mimicking a crosstalk between keratinocytes, stem cells and fibroblasts, as in skin. Beta-galactosidase assay, indicating the amount of senescent cells, and viability assay, revealed that fibroblasts and stem cells pretreated with NanoPCL-M and then exposed to UV are superimposable to control cells, untreated and unexposed to UV damage. On the other hand, cells only exposed to UV stress, without NanoPCL-M pretreatment, exhibited a significantly higher yield of senescent elements. Keratinocyte-based 3D structures appeared disjointed after UV-stress, as compared to NanoPCL-M pretreated samples. Gene expression analysis performed on different senescence associated genes, revealed the activation of a molecular program of rejuvenation in stem cells pretreated with NanoPCL-M and then exposed to UV. Altogether, our results highlight a future translational application of NanoPCL-M to prevent skin aging.

• MeSH
• exprese genu účinky léků   MeSH
• fibroblasty účinky léků   MeSH
• keratinocyty účinky léků   MeSH
• kmenové buňky účinky léků   MeSH
• kultivované buňky MeSH
• kůže účinky léků   MeSH
• lidé MeSH
• Myrtus chemie   MeSH
• nanovlákna chemie   MeSH
• polyestery chemie   MeSH
• proliferace buněk účinky léků   MeSH
• rostlinné extrakty farmakologie   MeSH
• stárnutí buněk účinky léků   MeSH
• stárnutí kůže účinky léků   MeSH
• ultrafialové záření škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Nivolumab is a human monoclonal antibody against programmed cell death receptor-1 (PD-1) able to rescue quiescent tumor infiltrating cytotoxic T lymphocytes (CTLs) restoring their ability to kill target cells expressing specific tumor antigen-derived epitope peptides bound to homologue human leukocyte antigen (HLA) molecules. Nivolumab is currently an active but expensive therapeutic agent for metastatic non-small cell lung cancer (mNSCLC), producing, in some cases, immune-related adverse events (irAEs). At the present, no reliable biomarkers have been validated to predict either treatment response or adverse events in treated patients. METHODS: We performed a retrospective multi-institutional analysis including 119 patients with mNSCLC who received PD-1 blockade since November 2015 to investigate the predictive role of germinal class I HLA and DRB1 genotype. We investigated the correlation among patients' outcome and irAEs frequency with specific HLA A, B, C and DRB1 alleles by reverse sequence-specific oligonucleotide (SSO) DNA typing. RESULTS: A poor outcome in patients negative for the expression of two most frequent HLA-A alleles was detected (HLA: HLA-A*01 and or A*02; progression-free survival (PFS): 7.5 (2.8 to 12.2) vs 15.9 (0 to 39.2) months, p=0.01). In particular, HLA-A*01-positive patients showed a prolonged PFS of 22.6 (10.2 to 35.0) and overall survival (OS) of 30.8 (7.7 to 53.9) months, respectively. We also reported that HLA-A and DRB1 locus heterozygosis (het) were correlated to a worse OS if we considered het in the locus A; in reverse, long survival was correlated to het in DRB1. CONCLUSIONS: This study demonstrate that class I and II HLA allele characterization to define tumor immunogenicity has relevant implications in predicting nivolumab efficacy in mNSCLC and provide the rationale for further prospective trials of cancer immunotherapy.

• MeSH
• alely MeSH
• analýza přežití MeSH
• HLA antigeny metabolismus   MeSH
• inhibitory kontrolních bodů farmakologie   terapeutické užití   MeSH
• lidé MeSH
• nádory plic genetika   mortalita   MeSH
• nemalobuněčný karcinom plic genetika   mortalita   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• výsledek terapie MeSH
• zárodečné mutace genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

Vitiligo is the most common depigmentation disorder of the skin. Currently, its therapy focuses on the halting of the immune response and stimulation of the regenerative processes, leading to the restoration of normal melanocyte function. Platelet-rich plasma (PRP) represents a safe and cheap regenerative therapy option, as it delivers a wide spectrum of native growth factors, cytokines and other bioactive molecules. The aim of this study was to develop a simple delivery system to prolong the effects of the bioactive molecules released from platelets. The surface of electrospun and centrifugally spun poly-ε-caprolactone (PCL) fibrous scaffolds was functionalized with various concentrations of platelets; the influence of the morphology of the scaffolds and the concentration of the released platelet-derived bioactive molecules on melanocytes, was then assessed. An almost two-fold increase in the amount of the released bioactive molecules was detected on the centrifugally spun vs. electrospun scaffolds, and a sustained 14-day release of the bioactive molecules was demonstrated. A strong concentration-dependent response of melanocyte to the bioactive molecules was observed; higher concentrations of bioactive molecules resulted in improved metabolic activity and proliferation of melanocytes. This simple system improves melanocyte viability, offers on-site preparation and is suitable for prolonged topical PRP administration.

• MeSH
• lékové transportní systémy * metody   MeSH
• lidé MeSH
• melanocyty MeSH
• plazma bohatá na destičky * MeSH
• vitiligo terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Hydrogels are suitable for osteochondral defect regeneration as they mimic the viscoelastic environment of cartilage. However, their biomechanical properties are not sufficient to withstand high mechanical forces. Therefore, we have prepared electrospun poly-ε-caprolactone-chitosan (PCL-chit) and poly(ethylene oxide)-chitosan (PEO-chit) nanofibers, and FTIR analysis confirmed successful blending of chitosan with other polymers. The biocompatibility of PCL-chit and PEO-chit scaffolds was tested; fibrochondrocytes and chondrocytes seeded on PCL-chit showed superior metabolic activity. The PCL-chit nanofibers were cryogenically grinded into microparticles (mean size of about 500 µm) and further modified by polyethylene glycol-biotin in order to bind the anti-CD44 antibody, a glycoprotein interacting with hyaluronic acid (PCL-chit-PEGb-antiCD44). The PCL-chit or PCL-chit-PEGb-antiCD44 microparticles were mixed with a composite gel (collagen/fibrin/platelet rich plasma) to improve its biomechanical properties. The storage modulus was higher in the composite gel with microparticles compared to fibrin. The Eloss of the composite gel and fibrin was higher than that of the composite gel with microparticles. The composite gel either with or without microparticles was further tested in vivo in a model of osteochondral defects in rabbits. PCL-chit-PEGb-antiCD44 significantly enhanced osteogenic regeneration, mainly by desmogenous ossification, but decreased chondrogenic differentiation in the defects. PCL-chit-PEGb showed a more homogeneous distribution of hyaline cartilage and enhanced hyaline cartilage differentiation.

• Publikační typ
• časopisecké články MeSH

Molecular profiling of a tumor allows the opportunity to design specific therapies which are able to interact only with cancer cells characterized by the accumulation of several genomic aberrations. This study investigates the usefulness of next-generation sequencing (NGS) and mutation-specific analysis methods for the detection of target genes for current therapies in non-small-cell lung cancer (NSCLC), metastatic colorectal cancer (mCRC), and melanoma patients. We focused our attention on EGFR, BRAF, KRAS, and BRAF genes for NSCLC, melanoma, and mCRC samples, respectively. Our study demonstrated that in about 2% of analyzed cases, the two techniques did not show the same or overlapping results. Two patients affected by mCRC resulted in wild-type (WT) for BRAF and two cases with NSCLC were WT for EGFR according to PGM analysis. In contrast, these samples were mutated for the evaluated genes using the therascreen test on Rotor-Gene Q. In conclusion, our experience suggests that it would be appropriate to confirm the WT status of the genes of interest with a more sensitive analysis method to avoid the presence of a small neoplastic clone and drive the clinician to correct patient monitoring.

• MeSH
• genom lidský genetika   MeSH
• iontové kanály MeSH
• lidé MeSH
• mutace genetika   MeSH
• nádory * diagnóza   genetika   MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

The biofunctionalization of scaffolds for tissue engineering is crucial to improve the results of regenerative therapies. This study compared the effect of platelet-functionalization of 2D electrospun and 3D centrifugal spun scaffolds on the osteogenic potential of hMSCs. Scaffolds prepared from poly-ε-caprolactone, using electrospinning and centrifugal spinning technology, were functionalized using five different concentrations of platelets. Cell proliferation, metabolic activity and osteogenic differentiation were tested using hMSCs cultured in differential and non-differential medium. The porous 3D structure of the centrifugal spun fibers resulted in higher cell proliferation. Furthermore, the functionalization of the scaffolds with platelets resulted in a dose-dependent increase in cell metabolic activity, proliferation and production of an osteogenic marker - alkaline phosphatase. The effect was further promoted by culture in an osteogenic differential medium. The increase in combination of both platelets and osteogenic media shows an improved osteoinduction by platelets in environments rich in inorganic phosphate and ascorbate. Nevertheless, the results of the study showed that the optimal concentration of platelets for induction of hMSC osteogenesis is in the range of 900-3000 × 109 platelets/L. The study determines the potential of electrospun and centrifugal spun fibers with adhered platelets, for use in bone tissue engineering.

• MeSH
• alkalická fosfatasa metabolismus   MeSH
• buněčná adheze MeSH
• buněčná diferenciace MeSH
• buněčné kultury MeSH
• lidé MeSH
• mezenchymální kmenové buňky cytologie   metabolismus   MeSH
• modul pružnosti MeSH
• osteogeneze MeSH
• polyestery chemie   MeSH
• poréznost MeSH
• proliferace buněk MeSH
• tkáňové inženýrství * MeSH
• tkáňové podpůrné struktury chemie   MeSH
• trombocyty cytologie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Aim: This study evaluates the effect of electrospun dressings in critical sized full-thickness skin defects in rabbits. Materials & methods: Electrospun poly-ε-caprolactone (PCL) and polyvinyl alcohol (PVA) nanofibers were tested in vitro and in vivo. Results: The PCL scaffold supported the proliferation of mesenchymal stem cells, fibroblasts and keratinocytes. The PVA scaffold showed significant swelling, high elongation capacity, limited protein adsorption and stimulation of cells. Nanofibrous dressings improved wound healing compared with the control group in vivo. A change of the PCL dressing every 7 days resulted in a decreased epithelial thickness and type I collagen level in the adhesive group, indicating peeling off of the newly formed tissue. In the PVA dressings, the exchange did not affect healing. Conclusion: The results demonstrate the importance of proper dressing exchange.

• MeSH
• buňky 3T3 MeSH
• hojení ran účinky léků   MeSH
• králíci MeSH
• kůže * zranění   metabolismus   patologie   MeSH
• myši MeSH
• nanovlákna chemie   MeSH
• obvazy * MeSH
• polyestery * chemie   farmakologie   MeSH
• polyvinylalkohol chemie   farmakologie   MeSH
• prasata MeSH
• tkáňová adheziva * chemie   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PURPOSE: Incisional hernia is the most common complication following abdominal surgery. While mesh repair is common, none of the current meshes mimic the physiology of the abdominal wall. This study compares suture only repair with polypropylene mesh and a prototype of a novel implant (poly-epsilon-caprolactone nanofibers) and their influence on the physiology of an abdominal wall in an animal model. METHODS: 27 Chinchilla rabbits were divided into six groups based on the type of the implant. Midline abdominal incision was repaired using one of the compared materials with suture alone serving as the control. 6 weeks post-surgery animals were killed and their explanted abdominal wall subjected to biomechanical testing. RESULTS: Both-hysteresis and maximum strength curves showed high elasticity and strength in groups where the novel implant was used. Polypropylene mesh proved as stiff and fragile compared to other groups. CONCLUSION: Poly-epsilon-caprolactone nanofiber scaffold is able to improve the dynamic properties of healing fascia with no loss of maximum tensile strength when compared to polypropylene mesh in an animal model.

• MeSH
• abdominální hernie * etiologie   chirurgie   MeSH
• abdominoplastika přístrojové vybavení   metody   MeSH
• chirurgické síťky * MeSH
• incizní kýla * etiologie   chirurgie   MeSH
• králíci MeSH
• modely nemocí na zvířatech MeSH
• nanovlákna terapeutické užití   MeSH
• operace kýly přístrojové vybavení   metody   MeSH
• pevnost v tahu MeSH
• polypropyleny terapeutické užití   MeSH
• pružnost MeSH
• testování materiálů MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Purpose: Incisional hernia repair is an unsuccessful field of surgery, with long-term recurrence rates reaching up to 50% regardless of technique or mesh material used. Various implants and their positioning within the abdominal wall pose numerous long-term complications that are difficult to treat due to their permanent nature and the chronic foreign body reaction they trigger. Materials mimicking the 3D structure of the extracellular matrix promote cell adhesion, proliferation, migration, and differentiation. Some electrospun nanofibrous scaffolds provide a topography of a natural extracellular matrix and are cost effective to manufacture. Materials and methods: A composite scaffold that was assembled out of a standard polypropylene hernia mesh and poly-ε-caprolactone (PCL) nanofibers was tested in a large animal model (minipig), and the final scar tissue was subjected to histological and biomechanical testing to verify our in vitro results published previously. Results: We have demonstrated that a layer of PCL nanofibers leads to tissue overgrowth and the formation of a thick fibrous plate around the implant. Collagen maturation is accelerated, and the final scar is more flexible and elastic than under a standard polypropylene mesh with less pronounced shrinkage observed. However, the samples with the composite scaffold were less resistant to distracting forces than when a standard mesh was used. We believe that the adverse effects could be caused due to the material assembly, as they do not comply with our previous results. Conclusion: We believe that PCL nanofibers on their own can cause enough fibroplasia to be used as a separate material without the polypropylene base, thus avoiding potential adverse effects caused by any added substances.

• MeSH
• břišní stěna chirurgie   MeSH
• chirurgické síťky * MeSH
• hernie * MeSH
• kolagen metabolismus   MeSH
• miniaturní prasata MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• nanovlákna chemie   MeSH
• operace kýly přístrojové vybavení   metody   MeSH
• polyestery MeSH
• polypropyleny chemie   MeSH
• prasata MeSH
• testování materiálů MeSH
• tkáňové podpůrné struktury chemie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH