Zwitterionic Biomaterials.

The term "zwitterionic polymers" refers to polymers that bear a pair of oppositely charged groups in their repeating units. When these oppositely charged groups are equally distributed at the molecular level, the molecules exhibit an overall neutral charge with a strong hydration effect via ionic solvation. The strong hydration effect constitutes the foundation of a series of exceptional properties of zwitterionic materials, including resistance to protein adsorption, lubrication at interfaces, promotion of protein stabilities, antifreezing in solutions, etc. As a result, zwitterionic materials have drawn great attention in biomedical and engineering applications in recent years. In this review, we give a comprehensive and panoramic overview of zwitterionic materials, covering the fundamentals of hydration and nonfouling behaviors, different types of zwitterionic surfaces and polymers, and their biomedical applications.

Exosomal circMACF1 drives PI3K/AKT/mTOR-mediated autophagy suppression in laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor. The regulatory functions of circular RNAs (circRNAs) in cancers have been broadly reported. The hsa_circ_0011773 (circMACF1) is reported to be overexpressed in LSCC tissues, while its biological function in LSCC remains unclear. CircMACF1 expression in LSCC tissues and cells was assessed via RT-qPCR. Exosomes extracted from cells were identified by TEM and NTA. Autophagy-related proteins were tested by western blot. Confocal microscope was employed for analyzing LC3 expression. Cell proliferation, migration, and invasion were assessed by CCK-8 assay and transwell assay. The levels of main proteins on PI3K/AKT/mTOR were tested by western blot. We observed that circMACF1 was highly expressed in LSCC tissues and cells. Furthermore, circMACF1 expression was also upregulated in the exosomes derived from LSCC cells. CircMACF1 depletion promoted LC3 expression in cells. Additionally, we proved that circMACF1 knockdown suppressed LSCC cell proliferative, migratory and invasive capabilities via promoting autophagy. Exosomal circMACF1 was found to promote LSCC tumor growth. Then, we proved that circMACF1 could activate PI3K/AKT/mTOR pathway to regulate autophagy. Moreover, MACF1 was positively regulated by circMACF1 and its overexpression notably reversed the effects of circMACF1 depletion in LSCC progression. Exosomal circMACF1 can regulate PI3K/AKT/mTOR-mediated autophagy suppression to facilitate LSCC development.

MOF-Based Antibiofouling Hemoadsorbent for Highly Efficient Removal of Protein-Bound Bilirubin.

A metal-organic framework (MOF)-based antibiofouling hemoadsorbent (PCB-MIL101) was developed through a facile encapsulation of MIL-101(Cr) in zwitterionic poly carboxybetaine (PCB) hydrogel. PCB-MIL101 possessed strong mechanical strength and superior hemocompatibility, ensuring its safety in hemoperfusion applications. In addition, it showed efficient and effective adsorption toward bilirubin (BR), and its maximum adsorption capacity was ∼583 mg g-1. Moreover, due to the protection of antibiofouling PCB hydrogel, PCB-MIL101 showed ability to resist protein adsorption, thus working effectively to remove BR molecules from their binding albumin in biological solutions. The finding in this study provides a novel insight into developing MOF-based hemoadsorbents for the improvement of hemoperfusion therapies.

Encapsulation of AgNPs within Zwitterionic Hydrogels for Highly Efficient and Antifouling Catalysis in Biological Environments.

Silver nanoparticles (AgNPs) have been widely used as catalysts in a variety of chemical reactions owing to their unique surface and electronic properties, but their practical applications have been hindered by severe aggregation. The immobilization of AgNPs is crucial to preventing their aggregation or precipitation as well as to improving their reusability. Herein, we developed a facile route for the reductant-free in situ synthesis of AgNPs in zwitterionic hydrogels. Via this method, the embedded AgNPs had a uniform distribution, high activity, and antibiofouling capability. The catalytic reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) using polycarboxybetaine-AgNPs (PCB-AgNPs) could achieve >95% conversion efficiency within 5 min. Meanwhile, the normalized rate constant knor (10.617 s-1mmol-1) was higher than that of most of the reported immobilized nanocatalysts. More importantly, in a biofouling environment, PCB-AgNPs could still exhibit >97% initial catalytic activity while AgNPs in the PSB or PHEMA hydrogel lost ∼60% activity. This strategy holds great potential for the immobilization of nanoparticle catalysts, especially for applications in biological environments.

Dimethyl Sulfoxide-Free Cryopreservation of Chondrocytes Based on Zwitterionic Molecule and Polymers.

Cartilage tissue engineering highly relies on the ability to store and transport chondrocytes in order to be clinically successful. Cryopreservation is a most reliable technology for chondrocyte storage, but it suffers from the intrinsic toxicity of current state-of-the-art cryoprotectant, dimethyl sulfoxide (DMSO). In this work, we used the first fully zwitterionic compound-based approach for effective chondrocyte cryopreservation. A zwitterionic molecule combined with zwitterionic polymers could balance intra/extracellular osmotic stress and prevent ice formation, which were the keys of successful cryopreservation. Moreover, this zwitterionic combination showed noncytotoxicity due to its high biocompatibility, superior to cytotoxic DMSO. On the basis of these performances, chondrocytes could be well cryopreserved (∼90% post-thaw survival efficiency) for a long time without any addition of DMSO, and the recovered cells could maintain their normal functionalities. In view of the association between polymer molecular weight and cryopreservation efficacy, further mechanism of cryoprotection provided by zwitterionic molecule/polymer was proposed. This work opens a new window of opportunity for DMSO-free cryopreservation using biocompatible zwitterionic materials.

A poly(hydroxyethyl methacrylate)-Ag nanoparticle porous hydrogel for simultaneous in vivo prevention of the foreign-body reaction and bacterial infection.

The use of implants or indwelling medical devices has greatly enhanced the quality and efficacy of health care. However, foreign-body reactions (FBRs) and infections can lead to potential failure or removal of the devices, or increased morbidity and mortality of patients. Herein, we develop a silver nanoparticle (AgNP) loaded poly(hydroxyethyl methacrylate) hydrogel with spherical, interconnected 40 µm pores. The resulting hydrogels displayed good antibacterial properties regarding both gram positive bacteria (Staphylococcus aureus) and gram negative bacteria (Escherichia coli (E. coli)) in vitro and were highly efficient at inhibiting bacterial cell growth. Moreover, they exhibited an in vivo resistance to FBRs by reducing the immune responses, and completely prevented the formation of collagen capsules. Finally, in vivo studies of the E. coli infected mouse model demonstrated that the AgNP loaded porous hydrogels were highly efficient at resisting the bacterial FBRs and infections, while they promoted cell mitigation and infiltration. Findings from this work suggest that AgNP loaded porous hydrogels hold promise in various biomedical applications including in the new generation of implantable biomedical devices and tissue engineering scaffolds.

Natural zwitterionic l-Carnitine as efficient cryoprotectant for solvent-free cell cryopreservation.

Organic solvents, such as dimethyl sulfoxide (DMSO) and glycerol, have been commonly used as cryoprotectants (CPAs) in cell cryopreservation. However, their cytotoxicity and need of complex freezing protocols have impeded their applications especially in clinical cell therapy and regenerative medicine. Trehalose has been explored as a natural CPA to cryopreserve cells, but its poor cell permeability frequently results in low cryopreservation efficacy. In this work, we presented that a natural zwitterionic molecule-l-carnitine-could serve as a promising CPA for solvent-free cryopreservation. We demonstrated that l-carnitine possessed strong ability to depress water freezing point, and with ultrarapid freezing protocol, we studied the post-thaw survival efficiency of four cell lines (GLC-82 cells, MCF-7 cells, NIH-3T3 cells and Sheep Red Blood Cells) using l-carnitine without addition of any organic solvents. At the optimum l-carnitine concentration, all four cell lines could achieve above 80% survival efficiency, compared with the significantly lower efficiency using organic CPAs and trehalose. After cryopreservation, the recovered cell behaviors including cell attachment and proliferation were found to be similar to the normal cells, indicating that the cell functionalities were not affected. Moreover, l-carnitine showed no observable cytotoxicity, which was superior to the organic CPAs. This work offered an attractive alternative to traditional CPAs and held great promise to revolutionize current cryopreservation technologies, to benefit the patients in various cell-based clinical applications.

The Value of Serum Complement C1q in the Diagnosis of Acute Ischemic Stroke.

BACKGROUND: To investigate the relationship between the levels of serum complement C1q and the risk and severity of acute ischemic stroke, a total of 154 patients with acute ischemic stroke and 42 healthy volunteers as normal controls were enrolled in the present study. METHODS: According to the onset time of stroke, patients were divided into three groups. Using an immune transmission turbidity method, the levels of serum complement C1q were detected to investigate the relationship between the level of serum complement C1q and the incidence and severity of acute ischemic stroke. The risk factors of these groups were calculated using a conditional logistic regression model. The assessment of neurological function impairment was carried out according to the National Institute of Health Stroke Scale. Then correlation anal- ysis was carried out between the level of serum complement C1q among patients with acute ischemic stroke and the degree of neurological function impairment. RESULTS: The results showed that the level of serum complement C1q was higher in the ischemic stroke group than in the control group. Using a conditional logistic regression model it was discovered that serum complement C1q was the independent pathogenic factor of cerebral infarction. There also was a decreasing trend in the level of serum complement C1q with the extension of the onset time and an increasing trend in the level of serum complement C1q with the increase in the maximum diameter of infarction volume. CONCLUSIONS: Serum complement C1q is an independent risk factor for acute outbreak of ischemic stroke, whose level is closely related to the outbreak and infarct size and neurological function impairment.

The preservation of living cells with biocompatible microparticles.

Biomedical applications of living cells have rapidly expanded in many fields such as toxic detection, drug screening, and regenerative medicine, etc. Efficient methods to support cell survival and maintain activity in vitro have become increasingly important. However, traditional cryopreservation for living cell-based applications is limited by several problems. Here, we report that magnetic hydrogel microparticles can physically assemble into a 3D environment for efficient cell preservation in physiological conditions, avoiding any chemical reactions that would damage the cells. Two representative cell lines (loosely and firmly adherent) were tested to evaluate the versatility of this method. The results showed that cell longevity was significantly extended to at least 15 days, while the control cell samples without microparticles quickly died within 3 days. Moreover, after preservation, cells can be easily retrieved by applying a magnet to separate the magnetic particles. This strategy can also inhibit cell over-proliferation while avoiding the use of temperature extremes or toxic cryoprotectants that are essential in cryopreservation.

Rib Composite Flap With Intercostal Nerve and Internal Thoracic Vessels for Mandibular Reconstruction.

PURPOSE: The purpose of this study was to present the outcome and discuss the feasibility of rib composite flap with intercostal nerve and internal thoracic vessels for reconstructing mandibular defect. METHODS: Rib composite flaps have been used in 82 patients for reconstructing benign tumor-caused large mandibular defects: 66 of the 82 patients were reconstructed using rib composite flap with intercostal nerve and internal thoracic vessels, whereas the other 16 patients were reconstructed using rib composite flap with internal thoracic vessels, without intercostal nerve. After operation, clinical observation, imageological examination, and sensory detection were used to evaluate the effect of reconstruction. RESULTS: All rib composite flaps with intercostal nerve and internal thoracic vessels were successfully harvested and transplanted. Both immediate and long-term examination showed good appearance reconstruction. All followed-up patients conveyed good satisfaction degree with function and appearance reconstruction. Postoperative panoramic x-ray examination showed new bone formation between the transplanted rib and mandibular stump. Good recoveries of mandibular nerve sensory were observed when followed up after reconstruction surgery. CONCLUSIONS: Rib composite flap with intercostal nerve and internal thoracic vessels could be a promising method for reconstruction of mandibular defects.

2D nanomaterial-based 3D network hydrogels for anti-infection therapy.

Two-dimensional nanomaterials (2D NMs) refer to nanomaterials that possess a planar topography with a thickness of one or several atomic layers. Due to their large specific surface areas, atomic thickness, rough edges, and electron confinement in two dimensions, they have emerged as promising antimicrobial agents over antibiotics in combating bacterial infections. However, 2D NMs encounter issues such as low bio-safety, easy aggregation, and limited tissue penetration efficiency. To address these concerns, hydrogels with three-dimensional (3D) networks have been developed to encapsulate 2D NMs, aiming to enhance their biocompatibility, biodegradability, and ability to regulate and remodel the tissue microenvironment at the infected site. This review systematically summarizes the current studies on 2D NM-based antibacterial hydrogels with 3D network structures (named 2N3Hs). Firstly, we introduce the emerging types of 2N3Hs and describe their antibacterial actions. Subsequently, we discuss the applications of 2N3Hs in three biomedical fields, including wound dressing, cancer treatment, and bone regeneration. Finally, we conclude the review with current challenges and future developments for 2N3Hs, highlighting their potential as a promising choice for next-generation biomedical devices, particularly in the field of tissue engineering and regenerative medicine. This review aims to provide a comprehensive and panoramic overview of anti-infective 2N3Hs for various biomedical applications.

Mucus and Biofilm Penetrating Nanoplatform as an Ultrasound-Induced Free Radical Initiator for Targeted Treatment of Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) infection is closely associated with the development of various gastric diseases. The effectiveness of current clinical antibiotic therapy is hampered by the rise of drug-resistant strains and the formation of H. pylori biofilm. This paper reports a sonodynamic nanocomposite PtCu3-PDA@AIPH@Fucoidan (PPAF), which consists of dopamine-modified inorganic sonosensitizers PtCu3, alkyl radicals (R•) generator AIPH and fucoidan, can penetrate the mucus layer, target H. pylori, disrupt biofilms, and exhibit excellent bactericidal ability. In vitro experiments demonstrate that PPAF exhibits excellent acoustic kinetic properties, generating a significant amount of reactive oxygen species and oxygen-independent R• for sterilization under ultrasound stimulation. Simultaneously, the produced N2 can enhance the cavitation effect, aiding PPAF nanoparticles in penetrating the gastric mucus layer and disrupting biofilm integrity. This disruption allows more PPAF nanoparticles to bind to biofilm bacteria, facilitating the eradication of H. pylori. In vivo experiments demonstrate that ultrasound-stimulated PPAF exhibited significant antibacterial efficacy against H. pylori. Moreover, it effectively modulated the expression levels of inflammatory factors and maintained gastrointestinal microbiota stability when compared to the antibiotic treatment group. In summary, PPAF nanoparticles present a potential alternative to antibiotics, offering an effective and healthy option for treating H. pylori infection.

Black Phosphorus-Based Conductive Hydrogels Assisted by Electrical Stimulus for Skin Tissue Engineering.

Conductive hydrogels have shown great potential in wound healing and skin tissue engineering, owing to their electroactive, mechanical, and chemical properties. However, it still remains as a challenge to incorporate other functions into conductive hydrogels, such as antibacterial ability, controllable drug release, and biodegradability. In this study, a black phosphorus-based conductive hydrogel (HA-DA@BP) is prepared by an amidation reaction coupled with a coordination of Fe3+ -catechol. The hydrogel could be changed from the sol phase to the gel phase under electrical stimulus (ES). The results show that BP could be released under slight acidity, which is cell compatible but could achieve synergistic electrical antibacterial action and promote wound healing. This study proves that BP is a strong candidate for electroactive materials and provides a new insight for the development of BP-based biomedical materials in skin tissue engineering.

Validation of combined AFP, AFP-L3, and PIVKA II for diagnosis and monitoring of hepatocellular carcinoma in Chinese patients.

Background: In this study, we aimed to investigate the performance of GALAD, GALAD-C, and GAAP models in Chinese population in comparison to our newly build statistical model. Methods: In this study, we built the AALP model based on age, α-fetoprotein (AFP), AFP-L3, and prothrombin induced by vitamin K absence-II (PIVKA II) to differentiate between patients with HCC and patients with CLD. We then compared the serum levels of AFP-L3 and PIVKA II in patients with HCC who were defined as remission or progression and showed the prognostic value of combined biomarkers. Results: The AUC value of the AALP model for HCC detection was 0.939 and AALP model exhibited a sensitivity of 81 % and a high specificity of 95 %. AALP model also exhibited good performance in the subgroups of patients with CLD. Furthermore, we demonstrated the consistency between imaging results and serum levels of AFP-L3 and PIVKA II. Conclusions: The AALP model achieved a good diagnostic performance and a high sensitivity for predicting HCC patients. Our research also showed that AFP-L3 and PIVKA II are complementary to each other but irreplaceable in the clinical detection and monitoring of HCC.

Reusable Zwitterionic Porous Organic Polymers for Bilirubin Removal in Serum.

Herein, we report a straightforward strategy to construct reusable, hemocompatible, and highly efficient bilirubin adsorbents by installing zwitterionic modules into a porous organic polymer (POP) for hemoperfusion application. Three types of zwitterions with different amounts are used to evaluate their impacts on the characteristics of POPs, including carboxybetaine methacrylate (CB), sulfobetaine methacrylate (SB), and 2-methacryloyloxyethyl phosphorylcholine (MPC). Results show that zwitterions can improve hemocompatibility, hydrophilicity, and bilirubin uptake of the POP. Among all zwitterionic POPs, POP-CB-40% exhibits the best bilirubin uptake, ∼46.5 times enhancement compared with the non-zwitterionic POP in 100% serum. This enhancement can be attributed to the improved hydrophilicity and protein resistance ability in biological solutions. More importantly, the reusability test shows that POP-CB-40% maintains ∼99% of bilirubin uptake capacity at fifth recycling in 100% serum. Findings in this work provide a guideline for the design of biocompatible and efficient POP-based bilirubin adsorbents for hemoperfusion therapy.

Functional carbohydrate-based hydrogels for diabetic wound therapy.

Diabetes wound are grave and universal complications of diabetes. Owing to poor treatment course, high amputation rate and mortality, diabetes wound treatment and care have become a global challenge. Wound dressings have received much attention due to their ease of use, good therapeutic effect, and low costs. Among them, carbohydrate-based hydrogels with excellent biocompatibility are considered to be the best candidates for wound dressings. Based on this, we first systematically summarized the problems and healing mechanism of diabetes wounds. Next, common treatment methods and wound dressings were discussed, and the application of various carbohydrate-based hydrogels and their corresponding functionalization (antibacterial, antioxidant, autoxidation and bioactive substance delivery) in the treatment of diabetes wounds were emphatically introduced. Ultimately, the future development of carbohydrate-based hydrogel dressings was proposed. This review aims to provide a deeper understanding of wound treatment and theoretical support for the design of hydrogel dressings.

Diagnostic value of combined serological markers in the detection of acute cerebral infarction.

ABSTRACT: To evaluate the value of the combination schemes of 10 serological markers in the clinical diagnosis of acute cerebral infarction.The level of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, homocysteine (HCY), lipoprotein-related phospholipase A2, ischemia-modified albumin, complement C1q, and lipoprotein a were analyzed in 154 patients with acute ischemic cerebral infarction. The optimized diagnostic combination for acute cerebral infarction was explored by calculating the maximum area under the receiver operating characteristic curves (AUC).The levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, HCY, lipoprotein-related phospholipase A2, ischemia-modified albumin, complement C1q, and lipoprotein a were significantly higher in the patient vs the control group. Moreover, the positive rate of HCY reached 89.9%. The analysis of the receiver operating characteristic curve of each index and their combinations showed that the minimum AUC of HDL-C alone was 0.543, while the maximum AUC of HCY was 0.853. A multiple logistic regression analysis indicated that HDL-C was a slightly significant variate in the diagnosis of acute cerebral infarction.The value of individual serological markers in the diagnosis of acute cerebral infarction was slightly significant, while the combination of the markers significantly improved the efficiency of its diagnosis.

2D Black Phosphorus-Based Cytomembrane Mimics with Stimuli-Responsive Antibacterial Action Inspired by Endotoxin-Associated Toxic Behavior.

Biomimetic membrane materials have been widely explored and developed for drug loading and tissue engineering applications due to their excellent biocompatibility and abundant reaction sites. However, novel cytomembrane mimics have been lacking for a long time. In this study, black phosphorus (BP) was used as the foundation for a new generation of promising cytomembrane mimics due to its multiple similarities to cytomembranes. Inspired by the dual function of endotoxins on membranes, we prepared a BP-based cytomembrane mimic with controllable antibacterial ability via electrostatic interaction between BP and [1-pentyl-1-quaternary ammonium-3-vinyl-imidazole]Br ([PQVI]Br). The release of PQVI could be manipulated in different conditions by adjusting the electrostatic force, thereby achieving controllable antibacterial ability. This report confirms the possibility of using BP as a new material to mimic cytomembranes and provides a new concept of controllable antibacterial action based on endotoxins.

Antifouling Fibrous Membrane Enables High Efficiency and High-Flux Microfiltration for Water Treatment.

Membrane biofouling has long been a major obstacle to highly efficient water treatment. The modification of the membrane surface with hydrophilic materials can effectively enhance biofouling resistance. However, the water flux of the membranes is often compromised for the improvement of antifouling properties. In this work, a composite membrane composed of a zwitterionic hydrogel and electrospinning fibers was prepared by a spin-coating and UV cross-linking process. At the optimum conditions, the composite membrane could effectively resist the biofouling contaminations, as well as purify polluted water containing bacteria or diatoms with a high flux (1349.2 ± 85.5 L m-2 h-1 for 106 CFU mL-1 of an Escherichia coli solution). Moreover, compared with the commercial poly(ether sulfone) (PES) membrane, the membrane displayed an outstanding long-term filtration performance with a lower water flux decline. Therefore, findings in this work provide an effective antifouling modification strategy for microfiltration membranes and hold great potential for developing antifouling membranes for water treatment.

A balanced charged hydrogel with anti-biofouling and antioxidant properties for treatment of irradiation-induced skin injury.

Skin injury caused by large doses of ionizing radiation is the common and severe side effect of radiotherapy. However, its therapeutic efficacy is always hindered by early reactive oxygen species generation, repetitive inflammatory microenvironment and bacterial infection risk. Herein, we report an anti-biofouling hydrogel with anti-inflammation and anti-oxidative properties for the treatment of irradiation-induced skin injury. The anti-biofouling hydrogel can be achieved by balancing oppositely charged alginate, hyaluronic acid (HA) and polylysine (PLL) at the optimal ratio, which effectively resist protein and bacterial adhesion, and evades immune response. Moreover, curcumin and epigallocatechin gallate (EGCG) can be facially encapsulated and substantially released from the hydrogel. Results showed that the resulting AHP-Cur/EGCG hydrogel can significantly weaken the development of skin injury and accelerate its healing process by alleviating inflammation, scavenging ROS and promoting angiogenesis. Therefore, the findings presented in this work provide an effective strategy for clinical management and treatment of ionizing radiation-induced skin injury.