A mussel inspired polyvinyl alcohol/collagen/tannic acid bioadhesive for wet adhesion and hemostasis.

Bioadhesives are useful in surgery for hemostasis, tissue sealing and wound healing. However, most bioadhesives have limitations such as weak adhesion in wet conditions, insufficient sealing and poor clotting performance. Inspired by the adhesion mechanism of marine mussels, a novel bioadhesive (PCT) was developed by simply combining polyvinyl alcohol (PVA), collagen (COL) and tannic acid (TA) together. The results showed that the adhesion, sealing and blood coagulation properties boosted with the increase of tannic acid content in PCT. The wet shear adhesion strength of PCT-5 (the weight ratio of PVA:COL:TA=1:1:5) was 60.8 ± 0.6 kPa, the burst pressure was 213.7 ± 0.7 mmHg, and the blood clotting index was 39.3% ± 0.6%, respectively. In rat heart hemostasis tests, PCT-5 stopped bleeding in 23.7 ± 3.2 s and reduced bleeding loss to 83.0 ± 19.1 mg, which outperformed the benchmarks of commercial gauze (53.3 ± 8.7 s and 483.0 ± 15.0 mg) and 3 M adhesive (Type No.1469SB, 35.3 ± 5.0 s and 264.0 ± 14.2 mg). The as-prepared bioadhesive could provide significant benefits for tissue sealing and hemorrhage control along its low cost and facile preparation process.

Significantly improved antifouling capability of silicone rubber surfaces by covalently bonded acrylated agarose towards biomedical applications.

Bacteria have the extraordinary ability to adhere to biomaterial surfaces and form multicellular structures known as biofilms, which have a detrimental impact on the performance of medical devices. Herein, an investigation highlighted the effective inhibition of bacteria adhesion and overgrowth on silicone rubber surface by grafting polysaccharide, agarose (AG), to construct hydrophilic and negatively charged surfaces. Because of the strong hydration capacity of agarose, the water contact angle of the modified silicone rubber surfaces was significantly reduced from 107.6 ± 2.7° to 19.3 ± 2.6°, which successfully limited bacterial adherence. Most importantly, the durability and stability of coating were observed after 10 days of simulated dynamic microenvironment in vivo, exhibiting a long service life. This modification method did not compromise biocompatibility of silicone rubber, opening a door to new applications for silicone rubber in the field of biomedical materials.

Heparinized anticoagulant coatings based on polyphenol-amine inspired chemistry for blood-contacting catheters.

Blood-contacting catheters occupy a vital position in modern clinical treatment including but not limited to cardiovascular diseases, but catheter-related thrombosis associated with high morbidity and mortality remains a major health concern. Hence, there is an urgent need for functionalized catheter surfaces with superior hemocompatibility that prevent protein adsorption and thrombus formation. In this work, we developed a strategy for constructing a kind of polyphenol-amine coating on the TPU surface (TLA) with tannic acid and lysine via simple dip-coating, inspired by dopamine adhesion. Based on the long-term stability and modifiable properties of TLA coatings, heparin was introduced by an amide reaction to provide anticoagulant activity (TLH). X-ray photoelectron spectroscopy and surface zeta potential measurements fully indicated the successful immobilization of heparin. Water contact angle measurements demonstrated good hydrophilicity and stability for 15 days of TLH coatings. Furthermore, the TLH coatings exhibited significant hemocompatibility and no cytotoxicity. The good antithrombotic properties of the functionalized surfaces were confirmed by an ex vivo blood circulation model. The present work is supposed to find potential clinical applications for preventing surface-induced thrombosis of blood-contacting catheters.

Quaternary tannic acid with improved leachability and biocompatibility for antibacterial medical thermoplastic polyurethane catheters.

The surfaces of indwelling catheters offer sites for the adherence of bacteria to form biofilms, leading to various infections. Therefore, the development of antibacterial materials for catheters is imperative. In this study, combining the strong antibacterial effect of a quaternary ammonium salt (QAS) and the high biocompatibility of tannic acid (TA), we prepared a quaternary tannic acid (QTA) by grafting a synthesized quaternary ammonium salt, dimethyl dodecyl 6-bromohexyl ammonium bromide, onto TA. To prepare antibacterial catheters, QTA was blended with thermoplastic polyurethane (TPU) via melt extrusion, which is a convenient and easy-to-control process. Characterization of the TPU blends showed that compared with those of the QAS, dissolution rate and biocompatibility of QTA were significantly improved. On the premise that the introduction of QTA had only a slight effect on the original mechanical properties of pristine TPU, the prepared TPU/QTA maintained satisfactory antibacterial activities in vitro, under a flow state, as well as in vivo. The results verified that the TPU/QTA blend with a QTA content of 4% is effective, durable, stable, and non-toxic, and exhibits significant potential as a raw material for catheters.

Bulk Modification of Thermoplastic Polyurethanes for Self-Sterilization of Trachea Intubation.

Implantable medical devices are widely used, but biomaterial-associated infections (BAIs) impose a huge economic burden and increase the mortality of patients. Therefore, BAIs are a serious concern that must be urgently resolved. Materials with antibacterial properties have become hotspots of current research and development. In the present work, quaternized chitosan (QCS) is used as an antibacterial agent and blended with thermoplastic polyurethane (TPU) to create an antibacterial material for tracheal intubation tubes. The modified TPU material (QCS-TPU) exhibited good mechanical properties and excellent long-term antibacterial performance. Under in vitro hydrodynamic conditions, QCS-TPU retained its strong antibacterial properties. QCS-TPU also possessed a low hemolysis rate and cytotoxicity. The current work is expected to provide a facile and feasible strategy for the preparation of antibacterial catheters and aid in the discovery of promising clinical applications to prevent BAIs.

Synthesis of Dimethyl Octyl Aminoethyl Ammonium Bromide and Preparation of Antibacterial ABS Composites for Fused Deposition Modeling.

Additive manufacturing (AM) demonstrates benefits in the high-precision production of devices with complicated structures, and the modification of materials for AM is an urgent need. To solve the bacterial infection of medical devices in their daily application, dimethyl octyl aminoethyl ammonium bromide (octyl-QDED), an organic antibacterial agent, was synthesized via the quaternary ammonium reaction. Then, the synthesized octyl-QDED was blended with acrylonitrile butadiene styrene (ABS) through the melt extrusion process to prepare antibacterial composite filaments for fused deposition modeling (FDM). The entire preparation processes were convenient and controllable. Characterizations of the structure and thermal stability of octyl-QDED confirmed its successful synthesis and application in the subsequent processes. The introduced maleic acid in the blending process acted as a compatibilizer, which improved the compatibility between the two phases. Characterizations of the rheological and mechanical properties proved that the addition of octyl-QDED made a slight difference to the comprehensive performance of the ABS matrix. When the content of octyl-QDED reached 3 phr, the composites showed excellent antibacterial properties. The prepared antibacterial composite filaments for FDM demonstrated great potential in medical and surgical areas.

Polycaprolactone/polysaccharide functional composites for low-temperature fused deposition modelling.

Fused deposition modelling (FDM) is a commonly used 3D printing technology. The development of FDM materials was essential for the product quality of FDM. In this work, a series of polycaprolactone (PCL)-based composites for low-temperature FDM were developed. By melt blending technique, different ratios of starch were added into PCL to improve the performances of FDM, and the printability, tensile strength, rheological properties, crystallization behaviors and biological performances of the composites were studied. The PCL/starch composite had the best performance in FDM process with the starch ratio of 9 ph at 80-90 °C. The melting strength and solidification rate of PCL/starch composites were improved. The starch also increased the crystallization temperature, degree of crystallinity and crystallization rate of PCL/starch composites, while had no negative effects on the tensile strength of PCL. Due to the low printing temperature, various kinds of bioactive components were added into PCL/starch composites for preparation of antibacterial and biocompatible materials for FDM. The present work provides a new method to develop novel low-temperature FDM materials with various functions.

Self-adaptive antibacterial surfaces with bacterium-triggered antifouling-bactericidal switching properties.

Catheter-induced infection is a severe problem in clinical practice, which induces significant morbidity, mortality and treatment costs. Therefore, there is a great requirement for developing antibacterial surfaces of catheter materials. In the present study, we develop a strategy for constructing self-adaptive antibacterial surfaces with bacterium-triggered antifouling-bactericidal switching properties on polyurethane (PU) via surface-initiated atom-transfer radical polymerization (SI-ATRP). Polymer coating with one hierarchical structure was readily constructed on the PU surface (PU-PQ-PEG), which was composed of poly[2-(dimethyl decyl ammonium)ethyl methacrylate] (PQDMAEMA) brushes as the bactericidal lower layer and polyethylene glycol (PEG) as the antifouling upper layer. The two layers were incorporated with Schiff base structures, which could be broken by the metabolism of bacteria. Under normal and mild infection conditions, PU-PQ-PEG showed excellent antifouling and biocompatible properties against proteins and bacteria. When serious infection occurred and bacteria colonized on the PU-PQ-PEG surface, the bacteria could trigger the self-adaptive antifouling-bactericidal switching of the surface. Furthermore, the self-adaptive antibacterial properties of PU-PQ-PEG were also confirmed by an in vitro circulating model to simulate hydrodynamic conditions. PU-PQ-PEG showed self-adaptive antibacterial performances both under static and hydrodynamic conditions. The results of animal experiments also demonstrated the in vivo anti-infection performance. The present work will provide a promising strategy for developing antibacterial surfaces of catheter materials with hemocompatibility.

Gradient Functionalization of Various Quaternized Polyethylenimines on Microfluidic Chips for the Rapid Appraisal of Antibacterial Potencies.

The ability to appraise antibacterial potencies of surface-immobilized bactericidal polymers is still a major challenge in the engineering of antibacterial surfaces to combat hospital-acquired (nosocomial) infections. In this work, we fabricated a microfluidic platform with gradiently immobilized bactericidal polymers to enable the rapid appraisal of antibacterial potencies by in situ live/dead staining of bacteria. To this end, a variety of synthetic quaternary polymers, named QPEI-C1, QPEI-C6, QPEI-C8, and QPEI-C10, were gradiently immobilized in microfluidic channels, and their surface densities at different distances along the channels were quantified by using fluorescein-labeled polymers. We found that the surface densities of quaternary polymers could be well-tuned, and the length of the channel, resulting in a 50% reduction of live bacteria (L50), can be used to appraise the antibacterial potency of each bactericidal polymer. For instance, the L50 values of QPEI-C6-, QPEI-C8-, and QPEI-C10-modified channels against Escherichia coli were 35.5, 44.7, and 49.2 mm, respectively, indicating that QPEI-C10 exerted the most potent antibacterial efficacy. More importantly, this microfluidic platform enabled the rapid discrimination of antibacterial potencies of polymers (e.g., QPEI-C8, and QPEI-C10) while the conventional live/dead staining method found no significant difference. This work provides a powerful toolkit by combining advances of microfluidic systems and polymer science for the rapid screening of antibacterial coatings, which would find applications in surface modification of medical devices to combat bacterial infections.

Tunable Adhesion of Different Cell Types Modulated by Thermoresponsive Polymer Brush Thickness.

Tunable adhesion of different cell types on well-defined surfaces has attracted common interests in the field of biomaterial science and surface engineering. Herein, we demonstrate a new strategy for the regulation of cell adhesion by simply controlling the thickness of thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) brushes via surface-initiated atom transfer radical polymerization (ATRP). The adhesion of different cell types (4T1, HEK293, H9C2, HUVEC, and L929) can be easily modulated by varying the thickness of PNIPAAm brushes from 5.9 ± 1.0 nm (PN1) to 69.0 ± 5.0 nm (PN6). The fluorescent staining of different cell types on a variety of surfaces reveals that the thickness of PNIPAAm brushes would regulate the assembly of F-actin and the expression of vinculin and fibronectin, which are essential in regulating the adherent status of cells. Moreover, the cellular morphologies revealed that the adherent cells are well-spread, and multiple pseudopod extensions and protrusions can be observed at the margin of cells. This work provides a facile strategy for regulating tunable adhesion of different cell types, which may find applications in tissue engineering and regenerative medicine.

Antimicrobial Peptide-Conjugated Hierarchical Antifouling Polymer Brushes for Functionalized Catheter Surfaces.

Catheter-related infection is a great challenge to modern medicine, which causes significant economic burden and increases patient morbidity. Hence, there is a great requirement for functionalized surfaces with inherently antibacterial properties and biocompatibility that prevent bacterial colonization and attachment of blood cells. Herein, we developed a strategy for constructing polymer brushes with hierarchical architecture on polyurethane (PU) via surface-initiated atom-transfer radical polymerization (SI-ATRP). Surface-functionalized PU (PU-DMH) was readily prepared, which comprised of poly(3-[dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azaniumyl]propane-1-sulfonate) (PDMAPS) brushes as the lower layer and antimicrobial peptide-conjugated poly(methacrylic acid) (PMAA) brushes as the upper layer. The PU-DMH surface showed excellent bactericidal property against both Gram-positive and Gram-negative bacteria and could prevent accumulation of bacterial debris on surfaces. Simultaneously, the PU-DMH samples possessed good hemocompatibility and low cytotoxicity. Furthermore, the integrated antifouling and bactericidal properties of PU-DMH under hydrodynamic conditions were confirmed by an in vitro circulating model. The functionalized surface possessed persistent antifouling and bactericidal performances both under static and hydrodynamic conditions. The microbiological and histological results of animal experiments also verified the in vivo anti-infection performance. The present work might find promising clinical applications for preventing catheter-related infection.

Facile Surface Multi-Functionalization of Biomedical Catheters with Dual-Microcrystalline Broad-Spectrum Antibacterial Drugs and Antifouling Poly(ethylene glycol) for Effective Inhibition of Bacterial Infections.

With the development of biomedical materials, the widespread use of implantable medical devices such as biomedical catheters has saved lives and improved therapeutic outcomes in the clinic. Biomedical catheters (BCs) have the ability to connect the body inside and outside and are widely used in clinical sites for fluid discharging, blood indwelling, mechanical ventilating, and so on. However, catheter-related infections (CRIs) are common nosocomial infections with high morbidity and mortality. The pathogens in the urinary tract, blood, and lung tissue carried by BCs may be the direct cause of CRIs, and the bacterial biofilm on the surface of BCs provides a notable source of persistent diseases. Microcrystalline sulfamethoxazole (SMZ) and trimethoprim (TMP) were prepared in this study to increase both the specific surface area and water-solubility of antibacterial drugs, as well as to enhance the antibacterial and antifouling effects on the surface of BCs. As-prepared drugs and the excellent antifouling agent polyethylene glycol (PEG) were then used for the functionalization of BCs. The result indicated that the sizes of microcrystalline SMZ and TMP were 0.5-3 µm, 1-5 µm, respectively. The coating of BC-PEG-drugs exhibited excellent antibacterial efficacy in culture as well as preeminent antibacterial and antifouling abilities on the surface of BCs toward Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Moreover, the BC-PEG-drugs groups exhibited outstanding antibacterial and antifouling abilities in vivo by an animal infection model with S. aureus. This study offers a simple and effective approach for the synthesis of antibacterial and antifouling coatings that consist of microcrystalline drugs, with promising clinical applicability.

Multifunctional Delivery Nanosystems Formed by Degradable Antibacterial Poly(Aspartic Acid) Derivatives for Infected Skin Defect Therapy.

Nucleic acid (NA)-based therapy is promising for tissue repair, such as skin and bone defect therapy. However, bacterial infections often occur in the process of tissue healing. The ideal treatment of tissue repair requires both anti-infection and simultaneous tissue healing. The epidermal growth factor (EGF) plays an important role in wound healing processes. In this work, degradable antibacterial gene vectors based on tobramycin (clinically relevant antibiotic) conjugated poly(aspartic acid) (TPT) are proposed as multifunctional delivery nanosystems of plasmid encoding EGF (pEGF) to realize the antibacterial therapy and tissue healing of infected skin defects. TPT has low cytotoxicity and good degradability, which is helpful in the NA delivery process. TPT demonstrates good transfection performances and hemocompatibility, as well as excellent antibacterial activities in vitro. The outstanding pEGF delivery ability of TPT and the bioactivity of expressed EGF facilitate the proliferation of fibroblast cells. The effective in vivo infected skin defect therapy is also demonstrated with TPT/pEGF nanocomplexes, where skin tissue healing is promoted. The present work opens new avenues for the design of multifunctional delivery nanosystems with antibacterial ability to treat infected tissue defect.

[A comparative study of mechanical properties of commercialized dental thermoplastic materials].

OBJECTIVE: To compare the mechanical properties of different dental optimal material selection for orthodontic appliance. METHODS: Four commercialized thermoplastic products under different test conditions, and provide the suggestion of thermoplastic products were tested. The tear strength, elongation at break and stress relaxation of these materials were measured under different test conditions. RESULTS: The tear strength declined after thermoforming, and rose again after 2 weeks of distilled water immersion. The elongation at break rose after thermoforming, and declined after 2 weeks of distilled water immersion. No significant changes were observed for brand A under different test conditions. Brand A showed the slowest stress relaxation of 0.0148 N/s. CONCLUSIONS: The mechanical properties of thermoplastic materials were influenced by environmental factors. Brand A exhibited optimal comprehensive properties.

Preparation and characterization of thermoplastic materials for invisible orthodontics.

PETG/PC/TPU polymer blend was prepared by mechanical blending. The mechanical properties of modified PETG/PC/TPU blend were characterized using a universal testing machine, and results were compared against two commercial thermoplastic products -Erkodur and Biolon. Blending modification improved the properties of PETG/PC/TPU. When blending ratio (wt%) was 70/10/20, PETG/PC/TPU exhibited optimal mechanical properties which exceeded those of Erkodur and Biolon. Tear strength was 50.23 MPa and elongation at break was 155.99%. Stress relaxation rate was 0.0136 N/s after 1 hour, which was significantly slower than Erkodur and Biolon (p<0.05). Water absorption rate was 0.57% after 2 weeks, which was significantly lower than Erkodur and Biolon (p<0.05).