In Vitro and In Vivo Assessment of the Infection Resistance and Biocompatibility of Small-Molecule-Modified Polyurethane Biomaterials.

Bacterial intracellular nucleotide second messenger signaling is involved in biofilm formation and regulates biofilm development. Interference with the bacterial nucleotide second messenger signaling provides a novel approach to control biofilm formation and limit microbial infection in medical devices. In this study, we tethered small-molecule derivatives of 4-arylazo-3,5-diamino-1H-pyrazole on polyurethane biomaterial surfaces and measured the biofilm resistance and initial biocompatibility of modified biomaterials in in vitro and in vivo settings. Results showed that small-molecule-modified surfaces significantly reduced the Staphylococcal epidermidis biofilm formation compared to unmodified surfaces and decreased the nucleotide levels of c-di-AMP in biofilm cells, suggesting that the tethered small molecules interfere with intracellular nucleotide signaling and inhibit biofilm formation. The hemocompatibility assay showed that the modified polyurethane films did not induce platelet activation or red blood cell hemolysis but significantly reduced plasma coagulation and platelet adhesion. The cytocompatibility assay with fibroblast cells showed that small-molecule-modified surfaces were noncytotoxic and cells appeared to be proliferating and growing on modified surfaces. In a 7-day subcutaneous infection rat model, the polymer samples were implanted in Wistar rats and inoculated with bacteria or PBS. Results show that modified polyurethane significantly reduced bacteria by ∼2.5 log units over unmodified films, and the modified polymers did not lead to additional irritation/toxicity to the animal tissues. Taken together, the results demonstrated that small molecules tethered on polymer surfaces remain active, and the modified polymers are biocompatible and resistant to microbial infection in vitro and in vivo.

L-cysteine aided polyaniline capped SrO2 nanoceramics: Assessment of MC3T3-E1-arbitrated osteogenesis and anti-bactericidal efficacy on the polyurethane 2D nanofibrous substrate.

Fabricating bioartificial bone graft ceramics retaining structural, mechanical, and bone induction properties akin to those of native stem-cell niches is a major challenge in the field of bone tissue engineering and regenerative medicine. Moreover, the developed materials are susceptible to microbial invasion leading to biomaterial-centered infections which might limit their clinical translation. Here, we successfully developed biomimetic porous scaffolds of polyurethane-reinforcedL-cysteine-anchored polyaniline capped strontium oxide nanoparticles to improve the scaffold's biocompatibility, osteo-regeneration, mechanical, and antibacterial properties. The engineered nanocomposite substrate PU/L-Cyst-SrO2 @PANI (0.4 wt%) significantly promotes bone repair and regeneration by modulating osteolysis and osteogenesis. ALP activity, collagen-I, ARS staining, as well as biomineralization of MC3T3-E1 cells, were used to assess the biocompatibility and cytocompatibility of the developed scaffolds in vitro, confirming that the scaffold provided a favorable microenvironment with a prominent effect on cell growth, proliferation, and differentiation. Furthermore, osteogenic protein markers were studied using qRT-PCR with expression levels of runt-related transcription factor 2 (RUNX2), secreted phosphoprotein 1 (Spp-I), and collagen type I (Col-I). The overall results suggest that PU/L-Cyst-SrO2 @PANI (0.4 wt%) scaffolds showed superior interfacial biocompatibility, antibacterial properties, load-bearing ability, and osteoinductivity as compared to pristine PU. Thus, prepared bioactive nanocomposite scaffolds perform as a promising biomaterial substrate for bone tissue regeneration.

Extracellular matrix-derived and low-cost proteins to improve polyurethane-based scaffolds for vascular grafts.

Vascular graft surgeries are often conducted in trauma cases, which has increased the demand for scaffolds with good biocompatibility profiles. Biodegradable scaffolds resembling the extracellular matrix (ECM) of blood vessels are promising vascular graft materials. In the present study, polyurethane (PU) was blended with ECM proteins collagen and elastin (Col-El) and gelatin (Gel) to produce fibrous scaffolds by using the rotary jet spinning (RJS) technique, and their effects on in vitro properties were evaluated. Morphological and structural characterization of the scaffolds was performed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Micrometric fibers with nanometric rugosity were obtained. Col-El and Gel reduced the mechanical strength and increased the hydrophilicity and degradation rates of PU. No platelet adhesion or activation was observed. The addition of proteins to the PU blend increased the viability, adhesion, and proliferation of human umbilical vein endothelial cells (HUVECs). Therefore, PU-Col-El and PU-Gel scaffolds are promising biomaterials for vascular graft applications.

Fabrication and assessment of a novel hybrid scaffold consisted of polyurethane-gellan gum-hyaluronic acid-glucosamine for meniscus tissue engineering.

The meniscus has inadequate intrinsic regenerative capacity and its damage can lead to degeneration of articular cartilage. Meniscus tissue engineering aims to restore an injured meniscus followed by returning its normal function through bioengineered scaffolds. In the present study, the structural and biological properties of 3D-printed polyurethane (PU) scaffolds dip-coated with gellan gum (GG), hyaluronic acid (HA), and glucosamine (GA) were investigated. The optimum concentration of GG was 3% (w/v) with maintaining porosity at 88.1%. The surface coating of GG-HA-GA onto the PU scaffolds increased the compression modulus from 30.30 kPa to 59.10 kPa, the water uptake ratio from 27.33% to 60.80%, degradation rate from 5.18% to 8.84%, whereas the contact angle was reduced from 104.8° to 59.3°. MTT assay, acridine orange/ethidium bromide (AO/EB) fluorescent staining, and SEM were adopted to assess the behavior of the seeded chondrocytes on scaffolds, and it was found that the ternary surface coating stimulated the cell proliferation, viability, and adhesion. Moreover, the coated scaffolds showed higher expression levels of collagen II and aggrecan genes at day 7 compared to the control groups. Therefore, the fabricated PU-3% (w/v) GG-HA-GA scaffold can be considered as a promising scaffold for meniscus tissue engineering.

Assessment of encrustation and physicochemical properties of poly(lactide-glycolide) - Papaverine hydrochloride coating on ureteral double-J stents after long-term flow of artificial urine.

Implantation of ureteral stents is associated with inconvenience for the patient, which is related to the natural ability of the ureter to contract. The most frequently used solution is the systemic administration of a diastolic drug, which has a relaxing effect on smooth muscle cells and decreases inconvenience. Current interdisciplinary research aimed at reducing the complications after the implantation of ureteral stents used in the treatment of upper urinary tracts with regard to infection, initiation of encrustation, and fragmentation of stents, and patient pain has not been resolved. This study presents the results of research regarding the impact of a biodegradable coating with the active substance on the physical and chemical properties of ureteral stents used in the treatment of the upper urinary tract. The surface of polyurethane double-J stents was coated with poly(lactide-glycolide) (PLGA) 85/15 loaded with papaverine hydrochloride (PAP) with diastolic properties. The coating for ureteral stents has been designed for short-term implantation. The effect of the coating on the process of encrustation and PAP release by the dynamic in vitro model with artificial urine (AU) up to 30 days was evaluated. The influence of AU on the physical and chemical properties of ureteral stents was determined. As part of the study, surface structure and topography researches; chemical composition analyses using X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and wetting; and surface roughness studies of both PUR stents and coated stents were carried out. The proposed biodegradable PLGA+PAP coating is characterized by controlled drug release, while optimal physicochemical properties does not increase the encrustation process.

Assessment of electrospun cardiac patches made with sacrificial particles and polyurethane-polycaprolactone blends.

Congenital heart defects (CHDs) are the leading cause of death in live-born infants. Currently, patches used in the repair of CHDs are exclusively inert and non-degradable, which increases the risk of arrhythmia, follow-up surgeries, and sudden cardiac death. In this preliminary study, we sought to fabricate biodegradable scaffolds that can support cardiac regeneration in the repair of CHDs. We electrospun biodegradable scaffolds using various blends of polyurethane (PU) and polycaprolactone (PCL) with and without sacrificial poly(ethylene oxide) (PEO) particles and assessed the mechanical properties, cell infiltration levels, and inflammatory response in vitro (surface cell seeding) and in vivo (subcutaneous mouse implant). We hypothesized that a blend of the two polymers would preserve the low stiffness of PU as well as the high cell infiltration observed in PCL scaffolds. The inclusion of PU in the blends, even as low as 10%, decreased cell infiltration both in vitro and in vivo. The inclusion of sacrificial PEO increased pore sizes, reduced Young's moduli, and reduced the inflammatory response in all scaffold types. Collectively, we have concluded that a PCL patch electrospun with sacrificial PEO particles is the most promising scaffold for further assessment as in our heart defect model.

Multifaceted Characterization And In Vitro Assessment Of Polyurethane-Based Electrospun Fibrous Composite For Bone Tissue Engineering.

INTRODUCTION: Recently several new approaches were emerging in bone tissue engineering to develop a substitute for remodelling the damaged tissue. In order to resemble the native extracellular matrix (ECM) of the human tissue, the bone scaffolds must possess necessary requirements like large surface area, interconnected pores and sufficient mechanical strength. MATERIALS AND METHODS: A novel bone scaffold has been developed using polyurethane (PE) added with wintergreen (WG) and titanium dioxide (TiO2). The developed nanocomposites were characterized through field emission scanning electron microscopy (FESEM), Fourier transform and infrared spectroscopy (FTIR), X-ray diffraction (XRD), contact angle measurement, thermogravimetric analysis (TGA), atomic force microscopy (AFM) and tensile testing. Furthermore, anticoagulant assays, cell viability analysis and calcium deposition were used to investigate the biological properties of the prepared hybrid nanocomposites. RESULTS: FESEM depicted the reduced fibre diameter for the electrospun PE/WG and PE/WG/TiO2 than the pristine PE. The addition of WG and TiO2 resulted in the alteration in peak intensity of PE as revealed in the FTIR. Wettability measurements showed the PE/WG showed decreased wettability and the PE/WG/TiO2 exhibited improved wettability than the pristine PE. TGA measurements showed the improved thermal behaviour for the PE with the addition of WG and TiO2. Surface analysis indicated that the composite has a smoother surface rather than the pristine PE. Further, the incorporation of WG and TiO2 improved the anticoagulant nature of the pristine PE. In vitro cytotoxicity assay has been performed using fibroblast cells which revealed that the electrospun composites showed good cell attachment and proliferation after 5 days. Moreover, the bone apatite formation study revealed the enhanced deposition of calcium content in the fabricated composites than the pristine PE. CONCLUSION: Fabricated nanocomposites rendered improved physico-chemical properties, biocompatibility and calcium deposition which are conducive for bone tissue engineering.

Chronic safety assessment of hemostatic self-expanding foam: 90-day survival study and intramuscular biocompatibility.

BACKGROUND: Noncompressible hemorrhage is a significant cause of preventable death in trauma, with no effective presurgical treatments. We previously described the efficacy and 28-day safety of a self-expanding hemostatic foam in swine models. We hypothesized that the 28-day results would be confirmed at a second site and that results would be consistent over 90 days. Finally, we hypothesized that the foam material would be biocompatible following intramuscular implantation. METHODS: Foam treatment was administered in swine following a closed-cavity splenic injury. The material was explanted after 3 hours, and the animals were monitored to 28 days (n = 6) or 90 days (n = 4). Results were compared with a control group with injury alone (n = 6 at 28 days, n = 3 at 90 days). In a separate study, foam samples were implanted in rabbit paravertebral muscle and assessed at 28 days and 90 days relative to a Food and Drug Administration-approved polyurethane mesh (n = 3 per group). RESULTS: All animals survived the acute phase of the study, and the foam animals required enterorrhaphy. One animal developed postoperative ileus and was euthanized; all other animals survived to the 28-day or 90-day end point without clinically significant complications. Histologic evaluation demonstrated that remnant particles were associated with a fibrotic capsule and mild inflammation. The foam was considered biocompatible in 28-day and 90-day intramuscular implant studies. CONCLUSION: Foam treatment was not associated with significant evidence of end-organ dysfunction or toxicity at 28 days or 90 days. Remnant foam particles were well tolerated. These results support the long-term safety of this intervention for severely bleeding patients.

Economically enhanced succinic acid fermentation from cassava bagasse hydrolysate using Corynebacterium glutamicum immobilized in porous polyurethane filler.

An immobilized fermentation system, using cassava bagasse hydrolysate (CBH) and mixed alkalis, was developed to achieve economical succinic acid production by Corynebacterium glutamicum. The C. glutamicum strains were immobilized in porous polyurethane filler (PPF). CBH was used efficiently as a carbon source instead of more expensive glucose. Moreover, as a novel method for regulating pH, the easily decomposing NaHCO3 was replaced by mixed alkalis (NaOH and Mg(OH)2) for succinic acid production by C. glutamicum. Using CBH and mixed alkalis in the immobilized batch fermentation system, succinic acid productivity of 0.42gL(-1)h(-1) was obtained from 35gL(-1) glucose of CBH, which is similar to that obtained with conventional free-cell fermentation with glucose and NaHCO3. In repeated batch fermentation, an average of 22.5gL(-1) succinic acid could be obtained from each batch, which demonstrated the enhanced stability of the immobilized C. glutamicum cells.

In vitro assessment of chlorhexidine gluconate-impregnated polyurethane foam antimicrobial dressing using zone of inhibition assays.

OBJECTIVE: To evaluate an antimicrobial dressing consisting of hydrophilic polyurethane foam with chlorhexidine gluconate for activity against several antibiotic-resistant clinical isolates as well as American Type Culture Collection reference strains using zone of inhibition assays. METHODS: Sterile foam samples with chlorhexidine gluconate and untreated controls were transferred onto inoculated agar plates. Plates were incubated at 35 degrees C to 37 degrees C for 24 hours and examined for zones of inhibition around the foam samples. RESULTS: Polyurethane foam with chlorhexidine gluconate showed antimicrobial activity in vitro against all of the challenge organisms including antibiotic-resistant clinical isolates. CONCLUSION: The data from this in vitro study support the hypothesis that polyurethane foam with chlorhexidine gluconate has an antimicrobial effect against antibiotic-resistant Staphylococcus and Enterococcus species, as well as Candida species.

An assessment of covalent grafting of RGD peptides to the surface of a compliant poly(carbonate-urea)urethane vascular conduit versus conventional biological coatings: its role in enhancing cellular retention.

The aim of sodding prosthetic grafts with endothelial cells (EC) is to establish a functioning antithrombogenic monolayer of EC. Application of basement membrane proteins improves EC adherence on ePTFE grafts. Their addition to a biodurable compliant poly(carbonate-urea)urethane graft (CPU) was studied with respect to EC adherence. Preclot, fibronectin, gelatin, and collagen were coated onto CPU. RGD peptide, heparin, and both RGD and heparin were chemically bonded to CPU. Human umbilical vein EC (HUVEC) labeled with 111-Indium oxine were sodded (1.8 x 10(6) EC/cm(2)) onto native and the modified CPU. The grafts were washed after 90 min and EC retention determined. The experiments were repeated six times. EC retention on native CPU was 1.0 +/- 0.2 x 10(5) EC/cm(2). The application of preclot, fibronectin, gelatin, and collagen did not improve EC retention, which was 0.8 +/- 0.1, 0.4 +/- 0.1, 0.3 +/- 0.08, and 0.5 +/- 0.2 x 10(5) EC/cm(2), respectively. Bonding RGD, heparin, and both RGD and heparin significantly improved EC retention to 1.9 +/- 0.6, 1.7 +/- 0.5, and 2.6 +/- 0.6 x 10(5) EC/cm(2), respectively (p < 0.01). Bonding of RGD, heparin, and both RGD and heparin accelerates and enhances EC retention onto CPU. Simple coating of basement membrane proteins confers no advantage over native CPU.

Comparison of hydrocellular foam and calcium alginate in the healing and comfort of split-thickness skin-graft donor sites.

This is a comparative study of a hydrocellular foam (Allevyn, Smith and Nephew) and a calcium alginate (Kaltostat, ConvaTec) in dressing split-thickness skin-graft donor sites. The dressing materials were used in equal halves of each donor site in 20 patients undergoing skin-graft harvest. The donor sites dressed with Allevyn showed a tendency to earlier healing, but this was not confirmed statistically. However, Allevyn was found to be more comfortable than Kaltostat and this difference was statistically significant. Due to its increased patient comfort, cheaper cost and comparable time to healing with Kaltostat, the authors recommend the use of Allevyn as a dressing for split-thickness skin-graft donor sites.