Low Protein Adsorption Research Articles

Stabilization and Kinetics of an Adsorbed Protein Depends on the Poly(N-isopropylacrylamide) Grafting Density.

The solubility transition at the lower critical solution temperature (LCST, 32 °C) of poly(N-isopropylacrylamide) (PNIPAM) is widely used as a thermal switch to rapidly and reversibly capture and release proteins and cells. It is generally assumed that proteins adsorbed to PNIPAM above the LCST are unaffected by polymer interactions. Here we show that the folding stability of the enzyme phosphoglycerate kinase (PGK) is increased by interactions with end-grafted PNIPAM films above the LCST. We systematically compare two protein mutants with different stabilities. The stabilization mirrors the degree of protein adsorption under grafting conditions studied previously. Maximum stabilization occurs when proteins adsorb to low density, collapsed polymer "mushrooms". In the denser polymer "brush" regime, protein stabilization decreases back to a value indistinguishable from the bulk solution, consistent with low protein adsorption on dense, collapsed brushes. The temperature-dependent kinetics measured by Fast Relaxation Imaging reveals that PNIPAM does not affect the overall folding/unfolding mechanism. Based on the different stabilizations of two mutants and the relaxation kinetics, we hypothesize that the polymer acts mainly by increasing the conformational entropy of the folded protein by interacting with the protein surface and less by crowding the unfolded state of PGK.

Enhancing antifouling property of reverse osmosis membranes via surface tethered with the aminated cation of ionic liquids

The electrical neutrality of ionic liquids (ILs) was exploited to enhance the antifouling property of polyamide (PA) reverse osmosis (RO) membranes in this work. We solely tethered the aminated imidazolium cation of ILs [AVIM] Br onto the top-surface of PA RO membranes via mild amidation. The molecular simulation results confirmed that the tethered imidazolium cation and the dissociated bromine anion were stably existed in the form of ion pairs on PA RO membrane surface. In virtue of the electrical neutrality of these ion pairs, the ionic-solvation induced hydration layer formed in ILs above the modified membrane surface was thick and evenly distributed, similar to that formed in conventionally electroneutral zwitterion antifouling materials. Thereby, the cation-tethered membrane surface intuitively achieved balanced charge and strong hydrophilicity, and stably exhibited low protein adsorption and excellent antifouling behaviors to diverse foulants, even when the imidazolium cation was paired with anions of different molecular size. Meanwhile, the typical ridge-and-valley surface morphology for PA RO membrane was well preserved due to the mild modification condition, and thereby harvested satisfactory separation performance. The integration of high performance, abundant ILs and mild conditions was expected to expand the application of superb antifouling materials in a variety of biofouling areas.

Construction of antifouling fluorinated polymer brush via activators regenerated by electron transfer ATRP and thiol-epoxy click reaction

In this work, fluorine containing polymer brushes was grafted on the functionalized stainless steel (SS) by activators regenerated by electron transfer atom transfer radical polymerization (ARGET-ATRP) and thiol-epoxy click reaction. PGMA brushes would be grafted on SS by coating the sheets with brominated polydopamine (PDA) as a reactive under-layer, and subsequently surface-initiate ARGET-ATRP of glycidyl methacrylate (GMA). Then the short-fluorinated alkyl chains were anchored on the PGMA backbones based on the click reaction between epoxy groups of PGMA and 1H, 1H, 2H, 2H-perfluorodecanethiol (PFDT), which endowed the surfaces of the polymers with low surface free energy. The surface compositions and morphologies of the functionalized SS have been characterized by attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM) and atomic force microscopy (AFM). The results of water contact angle analysis exhibited high hydrophobicity of the fluorinated polymer grafting modified SS surface. Bovine serum albumin (BSA) resistance performance of the functionalized SS was evaluated by BCA protein assay reagent, fluorescence microscope and XPS. The results exhibited that grafting fluoropolymer brushes modified SS with lower protein adsorption compared with the pristine SS surface, which might be served as promising environmentally friendly polymer antifouling coatings.

Superior anti-biofouling properties of mPEG-modified polyurethane networks via incorporation of a hydrophobic dangling chain

PEG-modification is a proven method to enhance the hydrophilicity, protein resistance, and anti-biofouling properties of polymer coatings. It is considered as the gold standard interfacial modification technique such that the higher PEG content, the higher hydrophilicity, and lower protein adsorption, i.e., the initial stage of the biofouling process. Nevertheless, increasing the PEG content causes a higher water uptake, which declines the polymer mechanical strength and increases its hydrolytic degradation rate. Thus, an effective strategy to produce a limited-water-absorbing PEG-modified polymer is to force the majority of PEG molecules to migrate towards the interfacial region while the modification takes place. In the current paper, we report the synthesis and characterization of crosslinked polycarbonate-based polyurethanes (PU) containing methoxy polyethylene glycol (mPEG) dangling chains. We show that the simultaneous incorporation of a limited amount of a low-surface-energy dangling chain, i.e., 1-octadecanol (oDEC), along with mPEG, results in a considerably higher mPEG surface concentration, according to X-ray photoelectron spectroscopy (XPS), and a significantly lower water contact angle (WCA), up to 45° lower. We also put forward a reasonable mechanism for our outstanding observation and verified it through extensive experiments, e.g., dynamic WCA, Atomic force microscopy (AFM), and XPS. Moreover, we outline a delicate dynamic WCA experimental protocol, by which the smart and responsive behavior of our coatings is illustrated. Eventually, we examined the mixed hydrophobic/hydrophilic dangling chains strategy for low-protein adsorption applications, in which a great potential has been discovered.

Favorable Antibacterial, Antibiofilm, Antiadhesion to Cells, and Biocompatible Polyurethane by Facile Surface Functionalization.

It is of paramount importance to prohibit biofilm formation in a wide range of implant devices, such as thermoplastic polyurethane (PU)-based catheters. It is possible only by means of a multifunctional material that provides fast and effective antibacterial activity, proper biocompatibility, and low bacterial and cell adhesion. In this paper, a facile chemistry approach has been developed to modify biomedical-grade PU with PU species, containing reactive uretdione functional groups for functionalization with the contact-type polyguanidine bactericidal agent and oxidized dextran as an antifouling polymer without sacrificing the thermal and mechanical properties. The resulting PU possesses broad-spectrum contact-active antibacterial activity against Gram-negative and Gram-positive bacteria with fast kinetics. The excellent antifouling capacity was confirmed by low nonspecific protein adsorption and reduced adhesion of fibroblast cells by ≥ 90%. In addition to antiadhesive and antibiofilm properties, high cell viability (>90%) and low hemolysis rate (HR < 1%) verified favorable cytocompatibility. Hence, the strategy followed to functionalize PUs in this paper might be considered to modify PU-based biomedical devices.

Facile fabrication of nanocarriers with yolk-shell mesoporous silica nanoparticles for effective drug delivery

Drug delivery systems (DDSs) can greatly reduce the negative impact of chemotherapy in the treatment of tumors by alleviating issues such as low solubility, short half-life, and strong side effects of chemotherapeutic drugs. Therefore, engineering DDSs is of great significance. Herein, we report an innovative magnetic delivery system with a yolk-shell structure and targeting function, comprising a magnetic core and a mesoporous silica shell. The yolk-shell-structure was fabricated by the swelling-shrinkage process of resorcinol-formaldehyde resin upon soaking in or removal of hexane, while a silica shell was formed. The hydrophobic resin layer, hollow cavity, and channels of the shell improved the drug loading and afforded sustained drug release. The desired drug carriers (denoted as Fe3O4@YSSiO2-FA) were labeled with folate to promote biocompatibility and targeting functions. The prepared Fe3O4@YSSiO2-FA with particle sizes ranging from 100 to 200 nm had a loading capacity of 220 μg mg−1 for camptothecin (CPT) and afforded sustained release over 72 h in vitro. Fe3O4@YSSiO2-FA presented a lower protein adsorption capacity, a hemolysis rate of less than 1.2%, and weak cytotoxicity for A549 cells, with a cell viability of more than 74%, indicating that the proposed nanocarriers possess excellent biocompatibility. CPT-loaded Fe3O4@YSSiO2-FA showed higher cytotoxicity for KB cells (FA-receptor-positive) due to the higher cellular uptake compared to A549 cells (FA-receptor-negative), likely suggesting a preeminent tumor-specific targeting ability. The superior loading capacity, targeting ability, and biocompatibility demonstrate that Fe3O4@YSSiO2-FA possesses great potential as a carrier for DDSs. As expected, the developed strategy provides a facile alternative for fabricating efficient DDSs for antitumor applications.

Brush Conformation of Polyethylene Glycol Determines the Stealth Effect of Nanocarriers in the Low Protein Adsorption Regime

For nanocarriers with low protein affinity, we show that the interaction of nanocarriers with cells is mainly affected by the density, the molecular weight, and the conformation of polyethylene glycol (PEG) chains bound to the nanocarrier surface. We achieve a reduction of nonspecific uptake of ovalbumin nanocarriers by dendritic cells using densely packed PEG chains with a “brush” conformation instead of the collapsed “mushroom” conformation. We also control to a minor extent the dysopsonin adsorption by tailoring the conformation of attached PEG on the nanocarriers. The brush conformation of PEG leads to a stealth behavior of the nanocarriers with inhibited uptake by phagocytic cells, which is a prerequisite for successful in vivo translation of nanomedicine to achieve long blood circulation and targeted delivery. We can clearly correlate the brush conformation of PEG with inhibited phagocytic uptake of the nanocarriers. This study shows that, in addition to the surface’s chemistry, the conformation of polymers controls cellular interactions of the nanocarriers.

Thermoresponsive zwitterionic poly(phosphobetaine) microgels: Effect of macro‐RAFT chain length and cross‐linker molecular weight on their antifouling properties

AbstractAdsorption of proteins on biological surfaces is a detrimental phenomenon that reduces the work‐life of the implants in various biomedical applications. Here, we synthesized a new class of thermoresponsive zwitterionic poly(phosphobetaine) (PMPC) microgel with excellent surface antifouling property by macro‐RAFT mediated thiol‐epoxy click reaction. End‐group modified zwitterionic PMPC homopolymers with well‐defined molecular weight and narrow dispersity were grafted onto poly(N‐vinylcaprolactam‐co‐glycidyl methacrylate) (PVG) copolymer backbone followed by addition of a cross‐linker, leading to microgel formation. While no upper critical solution temperature (UCST) was found in poly(N‐vinylcaprolactam‐co‐glycidyl methacrylate‐g‐2‐methacryloyloxyethyl phosphorylcholine) (PVGP) graft copolymers, the corresponding microgels exhibited both UCST and lower critical solution temperature (LCST) transitions, related to the swelling and collapse of PMPC and poly (N‐vinylcaprolactam) (PVCL) components respectively. An increase in the molecular chain length of the PMPC increased the shifting of UCST and LCST of the microgels to higher temperatures, due to the ability of zwitterionic groups to coordinate a large number of water molecules. The effect of the variation in the molecular weights of amphiphilic poly(ethylene glycol) diamine (PEG‐NH2) cross‐linker was also reflected in both temperature and salt responsiveness of the microgels. The efficacy of the microgels as potential antifouling materials was further studied by fluorescence microscopy and XPS analysis on microgel coatings treated with FITC‐BSA solution and pure BSA solution respectively. Lower protein adsorption was observed for microgels grafted with higher molecular chain length of PMPC, whereas, the microgels synthesized using higher molecular weight PEG‐NH2 diamine cross‐linker displayed greater protein adsorption on their surfaces.

Blood Oxygenation Using Fluoropolymer-Based Artificial Lung Membranes.

Artificial lung (AL) membranes are used for blood oxygenation for patients undergoing open-heart surgery or acute lung failures. Current AL technology employs polypropylene and polymethylpentene membranes. Although effective, these membranes suffer from low biocompatibility, leading to undesired blood coagulation and hemolysis over a long term. In this work, we propose a new generation of AL membranes based on amphiphobic fluoropolymers. We employed poly(vinylidene-co-hexafluoropropylene), or PVDF-co-HFP, to fabricate macrovoid-free membranes with an optimal pore size range of 30-50 nm. The phase inversion behavior of PVDF-co-HFP was investigated in detail for structural optimization. To improve the wetting stability of the membranes, the fabricated membranes were coated using Hyflon AD60X, a type of fluoropolymer with an extremely low surface energy. Hyflon-coated materials displayed very low protein adsorption and a high contact angle for both water and blood. In the hydrophobic spectrum, the data showed an inverse relationship between the surface free energy and protein adsorption, suggesting an appropriate direction with respect to biocompatibility for AL research. The blood oxygenation performance was assessed using animal sheep blood, and the fabricated fluoropolymer membranes showed competitive performance to that of commercial polyolefin membranes without any detectable hemolysis. The data also confirmed that the bottleneck in the blood oxygenation performance was not the membrane permeance but rather the rate of mass transfer in the blood phase, highlighting the importance of efficient module design.

Developing antibacterial superhydrophobic coatings based on polydimethylsiloxane/silver phosphate nanocomposites: Assessment of surface morphology, roughness and chemistry

Nanocomposite coatings based on polydimethylsiloxane (PDMS) and silver phosphate (Ag3PO4) nanoparticles were developed to achieve superhydrophobicity, antibacterial behavior and low protein adsorption. Since the as-synthesized nanoparticles were hydrophilic, octadecanethiol was added into the coatings’ solutions. Wettability results demonstrated that the higher the nanoparticle content, the higher the water contact angle (WCA). The highest WCA was observed for 7 wt% inclusion of nanoparticles (152°). Morphological analysis revealed the surface localization of nanoparticles and a packed structure in case of 7 wt% nanoparticle inclusion. From the roughness results, the ratio of texture surface area to cross-sectional area was found to be notably increased at higher nanoparticle contents. The presence of Ag3PO4 nanoparticles at the coatings’ top layer was confirmed by X-ray photoelectron spectroscopy. Antibacterial activity of the coatings significantly enhanced upon increasing the nanoparticle content. As a result of a true superhydrophobic (roll-off) behavior for 7 wt% nanoparticle inclusion, the protein adsorption was highly reduced (∼83 %) due to the enclosed air layer within the surface cavities leading to a lowered contact area of proteins with the coating’s surface. The combination of superhydrophobicity, antibacterial behavior and low protein adsorption leads to a biocompatible coating which could have many biomedical applications needing further investigations.

Effect of surface morphology change of polystyrene microspheres through etching on protein corona and phagocytic uptake

Surface physicochemistry properties of polymer particles are crucial for protein corona formation and macrophage phagocytosis when they contact with living body. In this work, polystyrene microspheres (PS-MSs) were selected as a model of polymer microparticles and fabricated by chromic acid etching through controlling conditions to obtain different surface morphology structures and to investigate their effect on the protein adsorption and phagocytic uptake of PS-MSs. The adsorption of bovine serum albumin (BSA) and fibrinogen (FIB) on PS-MSs showed almost the same tendency, i.e. the etched PS-MSs presented lower protein adsorption compared with original microspheres. The adsorption of BSA and FIB was the lowest when the protuberances on the etched surfaces were maximum and the size of the protuberances was minimum. Furthermore, the surface morphologies of PS-MSs were influenced in return not only by the amounts of proteins but also by protein types. Meanwhile, the macrophages phagocytosis of PS-MSs depended on the amounts and kinds of adsorbed proteins, especially the albumin content. In a word, phagocytosis and protein adsorption can be regulated by microsphere morphologies through etching, which provides a promising strategy to avoid invalid uptake for polymer particles such as drug delivery carriers.

PIP/TMC Interfacial Polymerization with Electrospray: Novel Loose Nanofiltration Membrane for Dye Wastewater Treatment.

A loose nanofiltration (NF) membrane with excellent dye rejection and high permeation of inorganic salt is required to fractionate dye/salt mixture in dye wastewater treatment. In this study, we fabricated the loose NF membrane by using the electrospray interfacial polymerization (EIP) method. It is a novel and facile interfacial polymerization method, which controls the thickness of the poly(piperazine-amide) (PPA) layer in nanometers (1 nm/min) and changes cross-linking degree of PPA layer and pore size by varying the electrospray time; consequently, water permeance and dye/salt rejection ratio can be handled. The fabricated EIP membrane with an optimized fabrication condition (M30, electrospray time was 30 min) possessed excellent pure water permeance (20.2 LMH/bar), high dye rejection (e.g., 99.6% for congo red (CR)), and low salt rejection (e.g., 6.3% for NaCl). Moreover, the EIP membrane exhibited enhanced antifouling property than commercial NF membrane (NF90) with a high flux recovery rate (FRR) of 87.1% and low irreversible fouling (Rir) of 12.9% after fouled by bovine serum albumin (BSA) due to its great smooth surface (average roughness (Ra) is 12.2 nm), hydrophilicity property, enhanced zeta potential, and low protein adsorption. The results indicate that the EIP loose NF membrane had a high potential for dye wastewater treatment.

Protein corona-mediated transport of nanoplastics in seawater-saturated porous media

The offshore aquaculture environment is a potential water area with high concentrations of tiny plastics and feeding proteins. In this study, the negatively charged bovine serum albumin (BSA) and the positively charged lysozyme (LSZ) were used to explore the effects of protein corona on the aggregation, transport, and retention of polystyrene nanoplastics (NPs; 200, 500, and 1000 nm) in sea sand saturated with seawater of 35 practical salinity units (PSU). The BSA corona, which was formed by the adsorption of BSA on the surface of NPs, drove the dispersion of NPs (200 and 500 nm) due dominantly to the induced colloidal steric hindrance. For example, the aggregate sizes of 500 nm NP decreased from 1740 ± 87 nm to 765 ± 8 nm at 40 min, which resulted in the enhanced transportation of NP. The calculated interaction energies indicated the BSA corona-induced high energy barriers (>104 KBT) between 1000 nm NPs and sand surface, demonstrating the BSA-enhanced transport of 1000 nm NPs. The mass percentage recovered from the effluent (Meff) increased from 33.4% to 61.7%. Inversely, the LSZ corona triggered the aggregation of 200 nm NPs into the large aggregates via electrostatic adsorption and bridging effect, thereby inhibiting the transport of 200 nm NPs. Nevertheless, no LSZ corona was formed on the surface of 500 and 1000 nm NPs due to extremely low protein adsorption. Accordingly, LSZ cannot affect the stability and transport of these NPs. In the diluted seawater (3.5 PSU), the strong electrostatic attraction between positively charged LSZ and 500 nm NPs significantly increased and the LSZ corona formed, which induced the aggregation of 500 nm NPs. The Meff of NPs therefore decreased from 53.1% to 11.2%. Overall, the protein corona-mediated transport of NPs in seawater-saturated porous media depends on protein type, NP size, and seawater salinity.

Charged group-modified poly(vinyl alcohol) hydrogels: Preparation and antibacterial property

Poly(vinyl alcohol) (PVA) hydrogels are widely employed in various biomedical applications due to their excellent biocompatibility, high water solubility, low protein adsorption, and chemical stability. In this work, two types of PVA-based hydrogels were synthesized by copolymerization of cationic [2-(methacryloyloxy) ethyl]trimethyl ammonium chloride (DMC) or zwitterionic sulfobetaine methacrylate (SBMA) with acrylated PVA (Acr-PVA), prepared through modification of the hydroxyl groups of PVA with glycidyl methacrylate (GMA). The antibacterial rates of Acr-PVA-g-PDMC hydrogels can reach 99.88% against Escherichia. coli and 99.99% against Staphylococcus. aureus. By comparison, the antibacterial rates of the Acr-PVA-g-PSBMA hydrogels can reach 88.40% against E. coli and 96% against S. aureus. Moreover, the Acr-PVA-g-PSBMA hydrogels possess better cell anti-adhesive properties than the Acr-PVA-g-PDMC hydrogels. The two types of hydrogels similarly possess macroporous structures, suitable swelling capacity, good mechanical properties and favorable cytocompatibility toward L929 cells. All results imply that charged group modified PVA hydrogels not only maintain the inherent properties of PVA but also possess excellent antibacterial and anti-adhesive properties. As such, the hydrogels show potential applications in biological materials fields.

High flux mixed matrix membrane with low albumin leakage for blood plasma detoxification

Current hemodialysis (HD) therapy removes well small sized toxins but removes less effectively middle molecules and protein-bound uremic toxins (PBUTs). This limited removal has been associated to high mortality of patients due to increased cardiovascular events. The hemodiafiltration therapy, which combines diffusive and convective transport using high flux membranes, can achieve higher removal of middle molecules. However, still the removal of PBUT is limited. Our earlier studies showed that combination of filtration and adsorption on one hollow fiber membrane, so called mixed matrix membranes (MMMs) can achieve removal of range of toxins, including PBUTs, however, these MMMs either had low flux and therefore were not suitable for convective therapies or had high flux but also albumin leakage which is undesired for the HD therapies. In this work, we present for the first time a new generation of MMM which combines high water flux with high albumin retention and very low total protein adsorption and protein leakage. The membrane fabrication conditions are optimized for achieving fibers with small diameter and optimal distribution of the sorbent particles leading to superior removal of PBUT from human plasma, in comparison to the previous MMMs, as well as, to series of commercial membranes used currently in the clinic.

Development of a polysulfone membrane with explicit characteristics for separation of low density lipoprotein from blood plasma

A polysulfone (PSf)-based membrane with a specific structure is developed by simultaneous combination of PVP-K90 as a hydrophilic high molecular weight (MW) polymer together with water as strong and glycerol as weak non-solvent additives, in order to separate low density lipoprotein (LDL) from blood plasma. Molecular weight cut-off (MWCO) and molecular weight retention onset (MWRO) of membranes were evaluated and found that membranes with 1.1×106 - 1.2 × 106 Da MWCO (M-W1, M-G3 and M-G4) displayed the best performance in current application. Assessment of mean pore size indicated that the membranes with 36–41 nm mean pore diameter had the best performance based on solute transport method. The membrane separation performance toward blood plasma exhibited that the optimized membranes could separate LDL from blood plasma by over 75%. Cardiovascular disease (CVD) risk factors verified that a specifically optimized membrane has a positive role in lowering CVD risks. The data acquired from plasma fractionation accompany with the scanning electron microscopy (SEM) studies revealed that a double-compartment nodular morphology was effective to separate LDL from smooth passage of other vital components in the blood plasma. Low protein adsorption, prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) demonstrated membranes hemocompatibility. Also, cell viability assay confirmed membranes biocompatibility.

Effect of surface chemistry on hMSC growth under xeno-free conditions

Human mesenchymal stem/stromal cells (hMSC) are promising therapeutic agents for regenerative medicine. However, therapeutic doses necessary for clinical application require in vitro expansion, ideally under Xeno-Free (XF) conditions to avoid the use of foetal bovine serum (FBS). We previously reported that hMSCs could be expanded using a pharmaceutical-grade human plasma-derived supplement for cell culture (SCC, Plastem®) combined with bFGF and TGFβ1, on fibronectin (Fn)-coated surfaces.hMSCs expansion may also be affected by the chemistry of the culture surface, which modulates protein adsorption at the cell-material interface and, consequently, cell behavior.This work aimed to evaluate the effect of surface chemistry on hMSCs behavior in SCC-based XF media. For that, self-assembled monolayers (SAMs) with hydrophobic (−CH3) and hydrophilic (neutral −OH, positively charged -NH3+ and negatively charged −COO−) groups were used as model surfaces.Under XF conditions, Fn coating showed to be necessary to improve hMSC adhesion (4 h) onto all surfaces, except for OH-SAMs, probably due to a low protein adsorption capacity characteristic of this surface. In terms of cell metabolic activity (5 days) on Fn-coated surfaces, an increase over time under XF conditions was observed in all SAMs except in CH3-SAMs, which can be attributed to strong and irreversible protein adsorption characteristic of hydrophobic surfaces. This trend was also observed under FBS conditions. Nevertheless, none of the surfaces improved hMSC metabolic activity, as compared with tissue-cultured surfaces. Overall, this work describes the role of surface chemistry in XF hMSC expansion.

α-Aminoisobutyric Acid-Stabilized Peptide SAMs with Low Nonspecific Protein Adsorption and Resistance against Marine Biofouling

A series of low fouling peptide self-assembled monolayers (SAMs) was developed to understand how the effects of subtle sequence alterations determine the properties of peptide-terminated SAMs and s...

Injectable zwitterionic thermosensitive hydrogels with low-protein adsorption and combined effect of photothermal-chemotherapy.

Injectable hydrogels have been developed as biomedical materials in various fields but the biofouling on their surface limits applications in vivo. In this work, a zwitterionic structure was introduced into an injectable hydrogel based on thermosensitive nanogels to overcome the foreign body reaction. The hydrodynamic diameter of the resultant poly(N-isopropylacrylamide-co-sulfobetaine methacrylate) (PNS) nanogels was ca. 105 nm. The aqueous dispersion with a high content of PNS nanogels showed a flowable sol state at room temperature, and turned into a hydrogel in situ at ∼36 °C due to the thermosensitivity of the PNS nanogels. In particular, the resulting hydrogel exhibited lower biofouling both in vitro and in vivo in comparison with similar hydrogels without a zwitterionic structure. Polydopamine nanoparticles (PDA NPs) as a photothermal agent and an anti-tumour drug could be easily co-loaded in the injectable hydrogel. Under near-infrared (NIR) irradiation for 10 min, the temperature of the PNS system containing PDA NPs could reach ca. 38 °C. The drug release from the in situ-forming hydrogel could be accelerated by NIR laser irradiation, and showed a sustainable release behavior and adjustability. The results of intratumoral injection of the as-prepared injectable hydrogel containing PDA NPs and an anti-tumour drug showed significant anticancer effects combining photothermal therapy and local chemotherapy. This constructed injectable zwitterionic thermosensitive hydrogel is easy to use with the advantage of low-fouling and may become a promising platform for various biomedical applications.

Alginate-Based Electrospun Membranes Containing ZnO Nanoparticles as Potential Wound Healing Patches: Biological, Mechanical, and Physicochemical Characterization.

In the present work, alginate-based mats with and without ZnO nanoparticles were prepared via an electrospinning technique and subjected to a washing-cross-linking process to obtain highly stable products characterized by thin and homogeneous nanofibers with a diameter of 100 ± 30 nm. Using a commercial collagen product as control, the biological response of the prepared mats was carefully evaluated with particular attention paid to the influence of the used cross-linking agent (Ca2+, Sr2+, or Ba2+ ions) and to the presence of nanofillers. Fibroblast and keratinocyte cultures successfully proved the safety of the prepared alginate-based mats, whereas ZnO nanoparticles were found to provide strong antibacteriostatic and antibacterial properties; above all, the strontium- and barium-cross-linked samples showed performances in terms of cell adhesion and growth very similar to those of the commercial collagen membrane despite them showing a significantly lower protein adsorption. Moreover, the mechanical and water-related properties of the strontium-cross-linked mats embedding ZnO nanoparticles were proven to be similar to those of human skin (i.e., Young modulus of 470 MPa and water vapor permeability of 3.8 × 10-12 g/m Pa s), thus proving the ability of the prepared mats to be able to endure considerable stress, maintaining at the same time the fundamental ability to remove exudates. Taking into account the obtained results, the proposed alginate-based products could lead to harmless and affordable surgical patches and wound dressing membranes with a simpler and safer production procedure than the commonly employed animal collagen-derived systems.