Ice recrystallization inhibition mechanism of zwitterionic poly(carboxybetaine methacrylate).

Understanding the ice recrystallization inhibition (IRI) mechanism is of fundamental importance for the rational design of novel antifreeze protein mimetics and reducing IR-related damage. In this communication, using quantitive experimental methods and molecular dynamics simulations we demonstrate that zwitterionic poly(carboxybetaine methacrylate) (PCBMA) can serve as a novel IRI-active substance. This work unravels the atomic-level details of the IRI mechanism of zwitterionic antifreeze protein mimetics and provides insight into the development of next-generation antifreeze protein mimetics.

Environment-Resistant Organohydrogel-Based Sensor Enables Highly Sensitive Strain, Temperature, and Humidity Responses.

Conductive hydrogels have been extensively used in wearable skin sensors owing to their outstanding flexibility, tissuelike compliance, and biocompatibility. However, the dehydration and embrittlement of hydrogels can result in sensitivity loss or even invalidation, restraining their wearable applications in external environments, especially at low temperatures and in arid environments. Herein, an environment-resistant organohydrogel is developed for multifunctional sensors. A double-network organohydrogel based on hyaluronic acid and poly(acrylic acid-co-acrylamide) is developed, and glycerol is introduced into the organohydrogel network via a solvent displacement strategy. Owing to the water-locking effects of glycerol and tough polymeric backbone, the resultant organohydrogel not only exhibits stable tensibility but also maintains excellent flexibility and stable conductivity with the environment-resistant properties, including freezing resistance against -30 °C and moisture retention at 4% relative humidity in a high temperature of 60 °C. Moreover, a series of organohydrogel-based sensors and an array device are developed to achieve highly sensitive strain, temperature, and humidity responses and exhibit a high gauge factor of 10.79 in the strain-sensitive test. This work develops a universal ionic skin based on organohydrogels to be applied to wearable sensors for health monitoring.

Zwitterionic peptide-functionalized highly dispersed carbon nanotubes for efficient wastewater treatment.

Multi-walled carbon nanotubes (MWCNTs) have displayed great potential as catalyst carriers due to their nanoscale structure and large specific surface area. However, their hydrophobicity and poor dispersibility in water restrict their applications in aqueous environments. Herein, the dispersibility of MWCNTs was significantly enhanced with a chimeric protein MPKE which consisted of a zwitterionic peptide unit and a mussel adhesive protein unit. The MPKE could be easily attached to MWCNTs (MPKE-MWCNTs) by a simple stirring process due to the versatile adhesion ability of mussel adhesive unit. As expected, the MPKE-MWCNTs displayed outstanding dispersibility in water (>7 months), as well as in alkaline solutions (pH = 12) and organic solvents (DMSO and ethanol) due to the hydrophilicity of the zwitterionic peptide unit. Moreover, the MPKE-MWCNTs were used as silver nanoparticle carriers for the reduction of 4-nitrophenol in wastewater, with the normalized rate constant knor up to 32.9 s-1 mmol-1. Meanwhile, they also exhibited excellent biocompatibility and antibacterial activity, which were favorable for wastewater treatment. This work provides a facile strategy for MWCNT modification, functionalization and applications in aqueous environments.

A zwitterionic hydrogel coated titanium surface with high-efficiency endothelial cell selectivity for rapid re-endothelialization.

Coronary stent implantation is an effective procedure for percutaneous coronary intervention treatment. However, its long-term safety and efficacy are still hindered by the in-stent restenosis and late thrombus formation. Herein, an anti-biofouling and endothelial cell selective zwitterionic hydrogel coating was developed to simultaneously enhance the nonspecific resistance and rapid re-endothelialization of the titanium surface. An endothelial cell selective peptide, REDV, could be simply conjugated on the zwitterionic carboxybetaine (CB) hydrogel to prepare the REDV/CB coating. It was found that the REDV/CB hydrogel layer maintained antifouling properties, which could inhibit the protein adsorption, bacterial adhesion, platelet activation and aggregation, and smooth muscle cell proliferation. More importantly, the co-culture study confirmed that the conjugated REVD peptide could specifically capture endothelial cells and promote their migration and proliferation, and simultaneously decrease the adhesion and proliferation of smooth muscle cells. Therefore, the antifouling and endothelial cell selective coating proposed in this work provides a promising strategy to develop an intravascular stent for promoted re-endothelialization and inhibited neointimal hyperplasia in clinical applications.

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.

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 Robust Cotton Textile-Based Material for High-Flux Oil-Water Separation.

PDMS-based materials have been extensively studied in oil-water separation. However, their successful application is commonly limited by low efficiency, vulnerability to acid/alkali, complex processing procedures, incapability for emulsion separation, etc. Here, a highly durable and robust separation material is developed by coating PDMS-based copolymers on cotton textiles with a facile sol-gel approach. Solely driven by gravity, this new material not only can enable effective separation of oil-water mixture with a flux as high as ∼7500 L m-2 h-1 but also can separate surfactant-stabilized water-in-oil emulsion. Moreover, it remains fully functional even in the environments with high concentrations of acid, alkali, or salt. This novel and versatile strategy holds great promise to be widely used in practical applications of oil-water separation, including oil/chemical spill accidents and industrial sewage emission.

A hemocompatible cryoprotectant inspired by freezing-tolerant plants.

Cryopreservation can extend the storage time of red blood cells (RBCs) for even decades, offering a promising solution to blood waste and shortage caused by routinely used hypothermic preservation method (˜42 days). Currently, organic solvents such as glycerol or dimethyl sulfoxide are the state-of-the-art cryoprotectants (CPAs). However, severe RBC hemolysis induced by solvent CPA removal has raised serious concerns, which has been the bottleneck problem for RBC cryopreservation. Here, inspired by freezing-tolerant plants, we reported a natural zwitterionic betaine-based approach for effective RBC cryopreservation without the need of any organic solvent. Using a time-saving ultrarapid freezing protocol, about 80% of post-thaw RBC integrity rate could be achieved. Most importantly, RBC integrity was not affected during betaine removal, indicating its hemocompatibility. Mechanistically, we presented that betaine could inhibit ice formation and recrystallization during freeze-thaw cycle to protect cells from ice injury; moreover, betaine probably could be promptly taken up and released by cells to prevent them from osmotic injury. This approach provides an attractive solution for long-distance/long-term RBC transport/storage, and may benefit current cryopreservation technologies to support the lifesaving RBC transfusion.

In Situ Encapsulation of Postcryopreserved Cells Using Alginate Polymer and Zwitterionic Betaine.

Currently, the state-of-the-art cryoprotectants for cell cryopreservation have bottleneck problems (such as cytotoxicity), which place enormous logistical limitations to the development of regenerative medicine. In this work, a first alginate polymer-based approach for human chondrocyte cryopreservation is reported. Combined with zwitterionic betaine, a natural osmoprotectant to offer intracellular protection, this alginate polymer-based approach can achieve ∼90% cryopreservation efficiency. Because of the biocompatibility of alginate polymer and betaine, this approach can easily retrieve the post-thaw cells without traditional multistep cryoprotectant washing procedures, which is highly favorable to cell therapy. Meanwhile, because of the feasible and mild gelation process of alginate polymer, this approach can also directly encapsulate the post-thaw cells into hydrogels without cryoprotectant removal, which is highly useful to tissue engineering. Moreover, these hydrogels exhibit tunable mechanical properties and can form variable shapes and sizes of scaffolds to inject into the patient's defect sites. After encapsulating post-thaw cells, these hydrogels can maintain high cell viability (∼90%) and normal cellular functions for at least 14 days. This work provides a step-change in cryopreservation of cells to be directly used in cell-based applications and may realize promising cellular therapy products that can integrate preservation with clinical practice.

Betaine Combined with Membrane Stabilizers Enables Solvent-Free Whole Blood Cryopreservation and One-Step Cryoprotectant Removal.

Cryopreservation of red blood cells (RBCs) is fundamentally important to modern transfusion medicine. Currently, organic solvent glycerol is utilized as the state-of-the-art cryoprotectant (CPA) for RBC cryopreservation. However, glycerol must be removed before RBC transfusion to avoid intravascular hemolysis via a time-consuming deglycerolization process with specialized equipment (e.g., ACP 215), thus limiting the clinical use of frozen RBCs. Herein, we report novel biocompatible CPA formulations combining betaine with membrane stabilizers (disaccharides or amino acids), which can achieve outstanding efficiency for RBC cryopreservation directly using whole blood without any separation process. Most importantly, because of the osmotic regulation capacity of betaine, a simple and fast one-step method can be used for CPA removal, which is significantly superior to the current multistep deglycerolization process. This work offers a promising solution for highly efficient and solvent-free RBC cryopreservation and holds great potential for improving the long-term storage and long-distance distribution of RBCs.

Exploring the Potential of Biocompatible Osmoprotectants as Highly Efficient Cryoprotectants.

Cryoprotectants (CPAs) are critical to successful cryopreservation because they can protect cells from cryoinjuries. Because of the limitations of current CPAs, especially the toxicity, the search for new effective CPAs is attracting increasing attention. In this work, we reported that natural biocompatible osmoprotectants, which could protect cells from osmotic injury in various biological systems, might also be ideal candidates for CPAs. Three representative biocompatible osmoprotectants (proline, glycine, and taurine) were tested and compared. It was found that, aside from presenting a different ability to prevent osmotic injury, these biocompatible osmoprotectants also possessed a different ability to inhibit ice formation and thus mitigate intra-/extracellular ice injury. Because of the strongest ability to prevent the two types of injuries, we found that proline performed the best in cryopreserving five different types of cells. Moreover, the natural osmoprotectants are intrinsically biocompatible with the cells, superior to the current state-of-the-art CPA, dimethyl sulfoxide (DMSO), which is a toxic organic solvent. This work opens a new window of opportunity for DMSO-free cryopreservation, and sheds light on the applications of osmoprotectants in cryoprotection, which may revolutionize the current cryopreservation technologies.

Factors associated with perforator stroke after selective basilar artery angioplasty or stenting.

BACKGROUND AND PURPOSE: Perforator stroke is one of the most common complications of elective intracranial angioplasty and/or stenting, particularly in the basilar artery. Factors associated with the risk of post-procedural perforator stroke remain unexplored. We investigated factors affecting the risk of perforator stroke after basilar artery angioplasty and/or stenting. MATERIALS AND METHODS: Consecutive patients undergoing basilar artery angioplasty and/or stenting due to symptomatic atherosclerotic stenosis were retrospectively included in this single-center study. Analyzed variables including demographic data, risk factors of atherosclerosis, symptoms, characteristics of imaging, and procedure factors were extracted from electronic health records or imaging data. The main outcome was perforator stroke associated with the procedure. Multivariate analysis that correlated factors with the occurrence of perforator stroke in these patients was performed. RESULTS: A total of 255 patients were included in the study. Perforator stroke associated with angioplasty and/or stenting was identified in 13 patients (5.1%). Variables with significant correlation with post-procedural perforator stroke included diabetes (OR 6.496; 95% CI 1.741 to 24.241; p=0.005), time from last symptom to procedure <18 days (OR 5.669; 95% CI 1.174 to 27.371; p=0.031), and pre-procedure stenosis percentage <88.4% (OR 5.882; 95% CI 1.465 to 23.608; p=0.012). CONCLUSIONS: Diabetes, time from last symptom to procedure, and pre-procedure stenosis percentage may be factors affecting the risk of perforator stroke associated with basilar artery angioplasty and/or stenting. These factors should be considered in planning of potential basilar artery angioplasty and/or stenting and prospectively evaluated in future multicenter trials.

The hypothermic preservation of mammalian cells with assembling extracellular-matrix-mimetic microparticles.

Hypothermic preservation at a refrigerated temperature allows feasible and flexible storage of living cells, and is of great importance for the widespread use of cell-based applications, such as cell diagnostics and cell therapy. The University of Wisconsin (UW) cold storage solution is one of the current state-of-the-art protectants for hypothermic cell preservation. However, even by using the UW solution, the current effective preservation time under refrigerated conditions is still no more than 1 or 2 days, which restraints larger geographic cell-sharing regions. Herein, we presented a facile technology based on the assembly of extracellular-matrix-mimetic microparticles, which can significantly enhance cell survival in hypothermic preservation under refrigerated conditions for at least 4 days. Moreover, compared with UW solution-based preservation, this strategy significantly inhibited cell nucleus deformation, indicating its ability to inhibit cell apoptosis. Furthermore, after being preserved, both the morphology and proliferation of the recovered cells were similar to normal cells. In addition, microparticle-based preservation could allow the free diffusion of nutrients and metabolic waste, and it was possible to easily and physically retrieve the cells using a permanent magnet. This new technology could significantly extend the preservation duration of cells and hold great promise to improve the outcome of cell therapy and diagnostic accuracy, which will benefit patients in various cell-based applications.