Influence of PEG Subunit on the Biological Activity of Ionenes: Synthesis of Novel Polycations, Antimicrobial and Toxicity Studies.

An alarming increase of antibiotic resistance among pathogens creates an urgent need to develop new antimicrobial agents. Many reported polycations show high antimicrobial activity along with low hemolytic activity. Unfortunately, most of those molecules remain highly cytotoxic against various mammalian cells. In this work, a systematic study on the impact of triethylene glycol monomethyl ether side groups (short polyethylene glycol (PEG) analog) on antimicrobial, hemolytic, and cytotoxic properties of novel amphiphilic ionenes is presented. A detailed description of synthesis, leading to well-defined alternating polymers, which differ in structural elements responsible for hydrophilicity (PEG) and hydrophobicity (alkyl chain), is presented. Obtained results show that the PEG moiety and fine-tuned hydrophilic-lipophilic balance of ionenes synergistically lead to low cytotoxic, low hemolytic molecules with high activity against S. aureus, including methicillin-resistant strains (MRSA). Additionally, the results of mechanistic studies on bacterial cells and fluorescently labeled liposomes are also discussed.

Impact of Porcine Pancreas Decellularization Conditions on the Quality of Obtained dECM.

Due to the limited number of organ donors, 3D printing of organs is a promising technique. Tissue engineering is increasingly using xenogeneic material for this purpose. This study was aimed at assessing the safety of decellularized porcine pancreas, together with the analysis of the risk of an undesirable immune response. We tested eight variants of the decellularization process. We determined the following impacts: rinsing agents (PBS/NH3·H2O), temperature conditions (4 °C/24 °C), and the grinding method of native material (ground/cut). To assess the quality of the extracellular matrix after the completed decellularization process, analyses of the following were performed: DNA concentration, fat content, microscopic evaluation, proteolysis, material cytotoxicity, and most importantly, the Triton X-100 content. Our analyses showed that we obtained a product with an extremely low detergent content with negligible residual DNA content. The obtained results confirmed the performed histological and immuno-fluorescence staining. Moreover, the TEM microscopic analysis proved that the correct collagen structure was preserved after the decellularization process. Based on the obtained results, we chose the most favorable variant in terms of quality and biology. The method we chose is an effective and safe method that gives a chance for the development of transplant and regenerative medicine.

Fenton-type reaction grafting of polyvinylpyrrolidone onto polypropylene membrane for improving hemo- and biocompatibility.

Known techniques for modification of polypropylene membranes (PPm) often require modification of the membrane in its entire volume (i.e. at the manufacturing stage), which may affect its properties. In the present work, the authors proposed a simple method for PPm hydrophilization. The process involves a two-step Fenton-type reaction, with ethylene glycol dimethacrylate (EGDMA) as a crosslinking agent and cumene hydroperoxide (CHP) as a source of free radicals. This hydrogel coating aims to enhance membrane hemocompatible and biocompatible properties. The biggest advantage of the proposed technique is the change of materials' surface properties, without interfering with its internal structure. Microscopic (SEM) and spectroscopic (FTIR-ATR) analyses confirmed the presence of hydrogel coating on PPm surfaces. Additionally, the evaluation of the surface density of the coating showed that the thickness of the coating increases with the reaction time and CHP concentration. The applied coatings significantly increase surface hydrophilicity (contact angle for PPm: 128.58°â€¯±â€¯0.52°, for all modified surfaces <53.31°â€¯±â€¯2.03°). The cytotoxicity test (XTT assay) proved biocompatibility of the PVP coating - cell viability remained above 90% for all variants tested. The modification resulted in a decrease in fibrinogen adsorption (of at least about 16%) and in a number of surface-adhered platelets. The assay evaluating the amount of secreted cell adhesion molecules (ICAM-1) showed a significant reduction (of at least about 50%) in the expression of ICAM-1 for all hydrogel-modified surfaces.

Patient specific implants for jawbone reconstruction after tumor resection.

In case of benign and malignant tumours affecting the maxillofacial region, the resection of jawbone reflects the standard therapy in more than 5.000 cases per year within the European Union. The resulting large bone defects lead to scarred, mangled facial appearance, loss of mastication and probably speech, requiring aesthetic and functional surgery as a basis for physical and physiological rehabilitation. Although autologous vascularized bone autografts reflect the current golden standard, the portion of bone available for the procedure is limited and subsequent high-dose anti-cancer chemo-/radiotherapy can lead to local tissue necrosis. Autologous vascularized bone from fibular or iliac-crest autografts is current golden standard in jawbone resection post-treatment, however, the portion of transplantable bone is limited and subsequent high-dose anti-cancer chemo-/radiotherapy often results in tissue necrosis Our research focuses on alternative treatment techniques: tissue reconstruction via novel patient-specifically manufactured maxillofacial implant that stimulates bone tissue growth. The planned neoformation of vascularized bone in such implants within the patient's own body as "bioreactor" is the safest approach in tissue engineering. The works described herein included the design of the metallic substrate of the implant with the use of computed tomography basing on real patients scans and then 3D-printing the substrates from the Ti6Al7Nb powder. The metal core was then evaluated in terms of structural characteristic, cytotoxicity and gene expression through the in vitro tests. Further experiments were focused on fabrication of the biocompatible coating for outer surface of the bone implant that would enhance the healing process and accelerate the tissue growth. Functional polymeric granulate dedicated for osteoconductive, osteoinductive and osteogenesis properties were elaborated. Another approach including the coating for the implant surface with two-phase biocompatible layer including polymeric microspheres and hydrogel carrier, which would provide long-time release of bone and cartilage growth factors around the implant were also done. The polymeric granulate containing ßTCP improved bone cells growth, but it some modification has to be done in order to improve structural pores to ensure for better osteoconductivity. The biocompatible coating including PVP hydrogel and polymeric microspheres is still in the development process.

Production of 3D printed polylactide scaffolds with surface grafted hydrogel coatings.

The aim of this work was to elaborate the 3D printed polylactide (PLA) polymeric scaffolds and, subsequently, study the possibility of coating thereof with a biomedical polyvinylpyrrolidone (PVP) hydrogel through the previously patented protocol. Such materials have a potential to be applied in biomedical engineering, e.g. for tissue regeneration. PVP layer according to the present paper could constitute a useful biocompatible supporting layer for drug delivering implant surfaces of any shape. Polylactide (PLA) both in forms of flat foils and 3D-printed scaffolds was used to be coated with PVP layer with the Fenton-type reaction that enables the polymeric scaffold grafting with hydrogel in two easy steps. The study revealed that PVP was successfully grafted to PLA substrates. Most optimal parameters for PVP grafting process were selected. The PLA-PVP materials were found to be hydrophilic and non-toxic which is promising considering their biomedical application. The method comprising well-tested PLA scaffolds printing and then grafting them with PVP layer has a promising potential to be brought in to the industrial production due to its simplicity.

Athrombogenic hydrogel coatings for medical devices--Examination of biological properties.

In the article the authors present hydrogel coatings prepared from polyvinylpyrrolidone (PVP) macromolecules, which are chemically bonded to polyurethane (PU) substrate. The coating is designed to improve the surface hemocompatibility of blood-contacting medical devices. The coating was characterized in terms of physical properties (swelling ratio, hydrogel density, surface morphology, coating thickness, coating durability). In order to examine surface hemocompatibility, the materials were contacted with whole human blood under arterial flow simulated conditions followed by calculation of platelet consumption and the number of platelet aggregates. Samples were also contacted with platelet-poor plasma; the number of surface-adsorbed fibrinogen molecules was measured using ELISA assay. Finally, the inflammatory reaction after implantation was assessed, using New Zealand rabbits. The designed coating is characterized by high water content and excellent durability in aqueous environment - over a 35-day period, no significant changes in coating thickness were observed. Experiments with blood proved twice the reduction in adsorption of serum-derived fibrinogen together with a moderate reduction in the number of platelet aggregates formed during the contact of the material with blood. The analysis of an inflammatory reaction after the implantation confirmed high biocompatibility of the fabricated materials - studies have shown no toxic effects of the implanted material on the surrounding animal tissues.