INTRODUCTION: The formation of diabetic ulcers (DU) is a common complication for diabetic patients resulting in serious chronic wounds. There is therefore, an urgent need for complex treatment of this problem. This study examines a bioactive wound dressing of a biodegradable electrospun nanofibrous blend of poly(L-lactide-co-ε-caprolactone) and poly(ε-caprolactone) (PLCL/PCL) covered by a thin fibrin layer for sustained delivery of bioactive molecules. METHODS: Electrospun PLCL/PCL nanofibers were coated with fibrin-based coating prepared by a controlled technique and enriched with human platelet lysate (hPL), fibroblast growth factor 2 (FGF), and vascular endothelial growth factor (VEGF). The coating was characterized by scanning electron microscopy and fluorescent microscopy. Protein content and its release rate and the effect on human saphenous vein endothelial cells (HSVEC) were evaluated. RESULTS: The highest protein amount is achieved by the coating of PLCL/PCL with a fibrin mesh containing 20% v/v hPL (NF20). The fibrin coating serves as an excellent scaffold to accumulate bioactive molecules from hPL such as PDGF-BB, fibronectin (Fn), and α-2 antiplasmin. The NF20 coating shows both fast and a sustained release of the attached bioactive molecules (Fn, VEGF, FGF). The dressing significantly increases the viability of human saphenous vein endothelial cells (HSVECs) cultivated on a collagen-based wound model. The exogenous addition of FGF and VEGF during the coating procedure further increases the HSVECs viability. In addition, the presence of α-2 antiplasmin significantly stabilizes the fibrin mesh and prevents its cleavage by plasmin. DISCUSSION: The NF20 coating supplemented with FGF and VEGF provides a promising wound dressing for the complex treatment of DU. The incorporation of various bioactive molecules from hPL and growth factors has great potential to support the healing processes by providing appropriate stimuli in the chronic wound.

• MeSH
• alfa-2-antiplasmin MeSH
• endoteliální buňky MeSH
• hojení ran MeSH
• lidé MeSH
• nanovlákna * MeSH
• obvazy MeSH
• polyestery farmakologie   MeSH
• vaskulární endoteliální růstový faktor A * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Pulmonary artery banding is a surgical procedure performed when there is a shunt between the left and right ventricle. Its aim is to constrict the lumen of the pulmonary artery by using a band to reduce blood flow to the lungs. In this study, we report the results of investigating the mechanical properties of a composite composed of poly(L-lactide-co-ε-caprolactone) layers and a collagen matrix (PLCL-COLL). PLCL layers were obtained by electrospinning, impregnated with collagen solution, and finally cross-linked to increase the stiffness of the material. Bands of PLCL-COLL were implanted into a rat peritoneum and explanted after 1, 3, and 6 months in vivo. The mechanical properties of the material before and after implantation were determined using uniaxial tensile tests. The same was done with samples of strips prepared from GORE-TEX material. By comparing the results of tensile tests before implantation and after explantation, it was found that PLCL-COLL degrades in the rat's body and that it exhibits a mechanical response showing of elastic modulus values that correspond well to arterial biomechanics (elastic modulus measured in the initial linear region of the deformation was found to be: 4.14 MPa ± 1.11 MPa, 2.34 MPa ± 1.02 MPa, 1.11 MPa ± 0.77 MPa, and 0.88 MPa ± 0.60 MPa before implantation, and 1, 3, and 6 months after implantation respectively). Similar to the elastic modulus, the strength of the PLCL-COLL composite decreased during in vivo exposure (1.32 ± 0.32 MPa, 0.60 ± 0.26 MPa, 0.44 ± 0.11 MPa, and 0.46 ± 0.28 MPa before implantation, and 1, 3, and 6 months after implantation respectively). In our experiments, PLCL-COLL material was always more compliant than GORE-TEX (elastic modulus 34.7 MPa ± 2.06 MPa before implantation, and 9.35 MPa ± 6.80 MPa after implantation). The results suggest that PLCL-COLL could be a suitable candidate for the development of artery banding tapes, and also for further use in cardiovascular surgery.

• MeSH
• arteria pulmonalis * chirurgie   MeSH
• biokompatibilní materiály chemie   MeSH
• biomechanika MeSH
• kolagen * chemie   metabolismus   MeSH
• krysa rodu rattus MeSH
• mechanické jevy * MeSH
• peritoneum * chirurgie   MeSH
• pevnost v tahu MeSH
• polyestery * chemie   metabolismus   MeSH
• testování materiálů MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Biodegradable polyesters, namely polycaprolactone (PCL) and copolymer of polylactide and polycaprolactone (PLCL) were electrospun into various fibrous structures and their hemocompatibility was evaluated in vitro. Firstly, hemolytic effect was evaluated upon incubation with diluted whole blood. The results showed that the degree of hemolysis depended on chemical composition and fibrous morphology. Electrospun polycaprolactone induced slight degree of hemolysis depending on its molecular weight and fibrous morphology; copolymer PLCL did not cause detectable hemolysis. The influence of coagulation pathways was examined by measurement of coagulation times. It was showed that intrinsic coagulation pathway assessed by activated partial thromboplastin time (APTT) was moderately accelerated after incubation with PCL and prolonged after incubation with copolymer PLCL. Extrinsic activation of coagulation tested by prothrombin time (PT) was slightly accelerated after incubation with all tested electrospun samples. Thrombogenicity assessment of fibrous samples revealed high thrombogenic properties of fibrous materials that was comparable to high degree of collagen thrombogenicity. The level of platelet activation was dependent on chemical composition and surface morphology of tested materials.

• MeSH
• biokompatibilní materiály chemická syntéza   chemie   farmakologie   MeSH
• hemolýza účinky léků   MeSH
• kolagen chemie   MeSH
• krevní buňky cytologie   účinky léků   metabolismus   MeSH
• lidé MeSH
• mikroskopie elektronová rastrovací MeSH
• parciální tromboplastinový čas MeSH
• polyestery chemie   MeSH
• polymery chemická syntéza   chemie   MeSH
• protrombinový čas MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The study involved the electrospinning of the copolymer poly(L-lactide-co-ε-caprolactone) (PLCL) into tubular grafts. The subsequent material characterization, including micro-computed tomography analysis, revealed a level of porosity of around 70%, with pore sizes of 9.34 ± 0.19 μm and fiber diameters of 5.58 ± 0.10 μm. Unlike fibrous polycaprolactone, the electrospun PLCL copolymer promoted fibroblast and endothelial cell adhesion and proliferation in vitro. Moreover, the regeneration of the vessel wall was detected following implantation and, after six months, the endothelialization of the lumen and the infiltration of arranged smooth muscle cells producing collagen was observed. However, the degradation rate was found to be accelerated in the rabbit animal model. The study was conducted under conditions that reflected the clinical requirements-the prostheses were sutured in the end-to-side fashion and the long-term end point of prosthesis healing was assessed. The regeneration of the vessel wall in terms of endothelialization, smooth cell infiltration and the presence of collagen fibers was observed after six months in vivo. A part of the grafts failed due to the rapid degradation rate of the PLCL copolymer.

• MeSH
• aorta patologie   MeSH
• arteriae carotides patologie   MeSH
• buněčná adheze MeSH
• buňky 3T3 MeSH
• cévní protézy * MeSH
• endoteliální buňky pupečníkové žíly (lidské) MeSH
• endoteliální buňky MeSH
• fibroblasty cytologie   MeSH
• kolagen metabolismus   MeSH
• králíci MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• myocyty hladké svaloviny cytologie   MeSH
• myši MeSH
• polyestery chemie   MeSH
• polymery chemie   MeSH
• poréznost MeSH
• prasata MeSH
• psi MeSH
• regenerace MeSH
• rentgenová mikrotomografie MeSH
• tkáňové inženýrství metody   MeSH
• tkáňové podpůrné struktury MeSH
• transplantace cév * MeSH
• zobrazování trojrozměrné MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• myši MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The study describes the detailed examination of the effect of ethylene oxide sterilization on electrospun scaffolds constructed from biodegradable polyesters. Different fibrous layers fabricated from polycaprolactone (PCL) and a copolymer consisting of polylactide and polycaprolactone (PLCL) were investigated for the determination of their mechanical properties, degradation rates and interaction with fibroblasts. It was discovered that the sterilization procedure influenced the mechanical properties of the electrospun PLCL copolymer scaffold to the greatest extent. No effect of ethylene oxide sterilization on degradation behavior was observed. However, a delayed fibroblast proliferation rate was noticed with concern to the ethylene oxide sterilized samples compared to the ethanol sterilization of the materials.

• MeSH
• biokompatibilní materiály chemie   metabolismus   farmakologie   MeSH
• buněčné linie MeSH
• cévní protézy MeSH
• ethylenoxid chemie   farmakologie   MeSH
• mikroskopie elektronová rastrovací MeSH
• modul pružnosti MeSH
• myši MeSH
• nanovlákna chemie   MeSH
• pevnost v tahu MeSH
• polyestery chemie   metabolismus   MeSH
• sterilizace MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The effectiveness of cell transplantation can be improved by optimization of the transplantation site. For some types of cells that form highly oxygen-demanding tissue, e.g., pancreatic islets, a successful engraftment depends on immediate and sufficient blood supply. This critical point can be avoided when cells are transplanted into a bioengineered pre-vascularized cavity which can be formed using a polymer scaffold. In our study, we tested surface-modified poly(lactide-co-caprolactone) (PLCL) capsular scaffolds containing the pro-angiogenic factor VEGF. After each modification step (i.e., amination and heparinization), the surface properties and morphology of scaffolds were characterized by ATR-FTIR and XPS spectroscopy, and by SEM and AFM. All modifications preserved the gross capsule morphology and maintained the open pore structure. Optimized aminolysis conditions decreased the Mw of PLCL only up to 10% while generating a sufficient number of NH2 groups required for the covalent immobilization of heparin. The heparin layer served as a VEGF reservoir with an in vitro VEGF release for at least four weeks. In vivo studies revealed that to obtain highly vascularized PLCL capsules (a) the optimal VEGF dose for the capsule was 50 μg and (b) the implantation time was four weeks when implanted into the greater omentum of Lewis rats; dense fibrous tissue accompanied by vessels completely infiltrated the scaffold and created sparse granulation tissue within the internal cavity of the capsule. The prepared pre-vascularized pouch enabled the islet graft survival and functioning for at least 50 days after islet transplantation. The proposed construct can be used to create a reliable pre-vascularized pouch for cell transplantation.

• MeSH
• bioinženýrství * MeSH
• experimentální diabetes mellitus chemicky indukované   metabolismus   patologie   MeSH
• fyziologická neovaskularizace * MeSH
• injekce intraperitoneální MeSH
• krevní glukóza analýza   MeSH
• krysa rodu rattus MeSH
• molekulární struktura MeSH
• polyestery chemie   metabolismus   MeSH
• potkani inbrední LEW MeSH
• streptozocin aplikace a dávkování   MeSH
• tobolky chemie   metabolismus   MeSH
• transplantace Langerhansových ostrůvků * MeSH
• vaskulární endoteliální růstové faktory chemie   metabolismus   MeSH
• velikost částic MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Chronic wounds affect millions of patients worldwide, and it is estimated that this number will increase steadily in the future due to population ageing. The research of new therapeutic approaches to wound healing includes the development of nanofibrous meshes and the use of platelet lysate (PL) to stimulate skin regeneration. This study considers a combination of a degradable electrospun nanofibrous blend of poly(L-lactide-co-ε-caprolactone) and poly(ε-caprolactone) (PLCL/PCL) membranes (NF) and fibrin loaded with various concentrations of PL aimed at the development of bioactive skin wound healing dressings. The cytocompatibility of the NF membranes, as well as the effect of PL, was evaluated in both monocultures and co-cultures of human keratinocytes and human endothelial cells. We determined that the keratinocytes were able to adhere on all the membranes, and their increased proliferation and differentiation was observed on the membranes that contained fibrin with at least 50% of PL (Fbg + PL) after 14 days. With respect to the co-culture experiments, the membranes with fibrin with 20% of PL were observed to enhance the metabolic activity of endothelial cells and their migration, and the proliferation and differentiation of keratinocytes. The results suggest that the newly developed NF combined with fibrin and PL, described in the study, provides a promising dressing for chronic wound healing purposes.

• Publikační typ
• časopisecké články MeSH

Chronic wounds affect millions of patients worldwide, and it is estimated that this number will increase steadily in the future due to population ageing. The research of new therapeutic approaches to wound healing includes the development of nanofibrous meshes and the use of platelet lysate (PL) to stimulate skin regeneration. This study considers a combination of a degradable electrospun nanofibrous blend of poly(L-lactide-co-ε-caprolactone) and poly(ε-caprolactone) (PLCL/PCL) membranes (NF) and fibrin loaded with various concentrations of PL aimed at the development of bioactive skin wound healing dressings. The cytocompatibility of the NF membranes, as well as the effect of PL, was evaluated in both monocultures and co-cultures of human keratinocytes and human endothelial cells. We determined that the keratinocytes were able to adhere on all the membranes, and their increased proliferation and differentiation was observed on the membranes that contained fibrin with at least 50% of PL (Fbg + PL) after 14 days. With respect to the co-culture experiments, the membranes with fibrin with 20% of PL were observed to enhance the metabolic activity of endothelial cells and their migration, and the proliferation and differentiation of keratinocytes. The results suggest that the newly developed NF combined with fibrin and PL, described in the study, provides a promising dressing for chronic wound healing purposes.

• Publikační typ
• časopisecké články MeSH

The integration of 3D printing into the pharmaceutical sciences opens new possibilities for personalized medicine. Poly(lactide) (PLA), a biodegradable and biocompatible polymer, is highly suitable for biomedical applications, particularly in the context of 3D printing. However, its processability often requires the addition of plasticizers. This study investigates the use of phase diagram modeling as a tool to guide the rational selection of plasticizers and to assess their impact on the thermodynamic and kinetic stability of PLA-based amorphous solid dispersions (ASDs) containing active pharmaceutical ingredients (APIs). Thermodynamic stability against API recrystallization was predicted based on the API solubility in PLA and Plasticizer-PLA carriers using the Conductor-like Screening Model for Real Solvents (COSMO-RS), while the kinetic stability of the ASDs was evaluated by modeling the glass transition temperatures of the mixtures. Two APIs, indomethacin (IND) and naproxen (NAP), with differing glass-forming abilities (i.e., recrystallization tendencies), and three plasticizers, triacetin (TA), triethyl citrate (TEC), and poly(L-lactide-co-caprolactone) (PLCL), were selected for investigation. The physical stability of ASD formulations containing 9 wt% API and plasticizer to PLA in two ratios, 10:81 and 20:71 w/w %, was monitored over time using differential scanning calorimetry and X-ray powder diffraction and compared with phase diagram predictions. All formulations were predicted to be thermodynamically unstable; however, those containing no plasticizer or with TEC and TA at 10 wt% were predicted to exhibit some degree of kinetic stability. Long-term physical studies corroborated these predictions. The correlation between the predicted phase behavior and long-term physical stability highlights the potential of phase diagram modeling as a tool for the rational design of ASDs in pharmaceutical 3D printing.

• MeSH
• 3D tisk * MeSH
• citráty chemie   MeSH
• diferenciální skenovací kalorimetrie metody   MeSH
• farmaceutická chemie metody   MeSH
• farmaceutická technologie metody   MeSH
• indomethacin * chemie   MeSH
• krystalizace MeSH
• naproxen chemie   MeSH
• polyestery * chemie   MeSH
• rozpouštědla chemie   MeSH
• rozpustnost * MeSH
• stabilita léku MeSH
• termodynamika MeSH
• tranzitní teplota MeSH
• triacetin chemie   MeSH
• změkčovadla * chemie   MeSH
• Publikační typ
• časopisecké články MeSH