Functional Zwitterionic Polyurethanes: State-of-the-Art Review.

Recent advancements in bioengineering and medical devices have been greatly influenced and dominated by synthetic polymers, particularly polyurethanes (PUs). PUs offer customizable mechanical properties and long-term stability, but their inherent hydrophobic nature poses challenges in practically biological application processes, such as interface high friction, strong protein adsorption, and thrombosis. To address these issues, surface modifications of PUs for generating functionally hydrophilic layers have received widespread attention, but the durability of generated surface functionality is poor due to irreversible mechanical wear or biodegradation. As a result, numerous researchers have investigated bulk modification techniques to incorporate zwitterionic polymers or groups onto the main or side chains of PUs, thereby improving their hydrophilicity and biocompatibility. This comprehensive review presents an extensive overview of notable zwitterionic PUs (ZPUs), including those based on phosphorylcholine, sulfobetaine, and carboxybetaine. The review explores their wide range of biomedical applications, from blood-contacting devices to antibacterial coatings, fouling-resistant marine coatings, separation membranes, lubricated surfaces, and shape memory and self-healing materials. Lastly, the review summarizes the challenges and future prospects of ZPUs in biological applications.

Synthesis and characterization of thermosensitive 2-hydroxypropyl-trimethylammonium chitin and its antibacterial sponge for noncompressible hemostasis and tissue regeneration.

Noncompressible hemorrhage is a leading cause of preventable death in battlefield/civilian trauma. The development of novel injectable and biodegradable hemostatic sponges, with rapid shape recovery and excellent antibacterial activity that can control hemorrhage in noncompressible bleeding sites and promote in situ tissue regeneration is still urgently needed. In this study, thermo/pH sensitive 2-hydroxypropyl-trimethylammonium chitins (QCHs) with low degree of quaternization substitution (DS: 0.07-0.23) and high degree of acetylation (DA: 0.91-0.94) were synthesized homogeneously for the first time. Their chemical compositions including DS and DA were characterized accurately by proton NMR for the first time. High strength QCH based sponges with good water/blood absorbency, rapid shape recovery and good antibacterial activity were prepared without using any crosslinkers but only due to their thermosensitive property, since they are soluble at low temperature but insoluble at high temperature. Compared with commercial products, the QCH sponges with cationic groups had the stronger pro-coagulant ability, better hemostatic effect in normal/heparinized liver perforation and femoral artery models in rats and porcine subclavian arteriovenous resection model. Moreover, the porous structure and biodegradability of the QCH sponges could promote in situ tissue regeneration. Overall, the QCH sponges show great clinical translational potential for noncompressible hemorrhage and tissue regeneration.

Association of weight-adjusted waist index and diabetic kidney disease in type 2 diabetes mellitus.

Objective: The aim of this study was to investigate the relationship between weight-adjusted-waist index (WWI) and diabetic kidney disease in individuals afflicted with type 2 diabetes. Methods: Comprehensive data were ascertained from the National Health and Nutrition Examination Survey in 2013-March 2020. Weighted univariate, multivariate logistic regression models, subgroup analyses and tests for interaction were performed. Additionally, we employed smooth curve fitting to assess linear correlations and the threshold effects were calculated by applying a binary linear regression model. Breakpoints are identified by a model with maximum likelihood ratio and a two-step recursive approach. Receiver operating characteristic curve (ROC) along with the area under the curve (AUC) value predict the capability of WWI and body mass index for diabetic kidney disease. Results: A total of 10,661 individuals diagnosed with type 2 diabetes were included, and the overall prevalence of diabetic kidney disease was 20.74%. WWI exhibited a positive correlation with the likelihood of diabetic kidney disease in type 2 diabetes patients (OR: 1.17, 95% CI: 1.03-1.33). The results of subgroup analysis showed significant interaction for gender (P < 0.05). Among female patients, U-shaped correlations were observed with a breakpoint at 11.48. Additionally, weight-adjusted waist index (AUC = 0.664) proved to be a more effective predictor of diabetic kidney disease compared to body mass index (AUC = 0.555). Conclusion: In patients with type 2 diabetes, increased weight-adjusted-waist index is implicated with an increased risk of diabetic kidney disease. WWI can be used as a new anthropometric index to predict diabetic kidney disease, and its predictive ability is stronger than body mass index.

Surface functionalization of polyurethanes: A critical review.

Synthetic polymers, particularly polyurethanes (PUs), have revolutionized bioengineering and biomedical devices due to their customizable mechanical properties and long-term stability. However, the inherent hydrophobic nature of PU surfaces arises common issues such as high friction, strong protein adsorption, and thrombosis, especially in the physiological environment of blood contact. To overcome these issues, researchers have explored various modification techniques to improve the surface biofunctionality of PUs. In this review, we have systematically summarized several typical surface modification methods including surface plasma modification, surface oxidation-induced grafting polymerization, isocyanate-based chemistry coupling, UV-induced surface grafting polymerization, adhesives-assisted attachment strategy, small molecules-bridge grafting, solvent evaporation technique, and hydrogen bonding interaction. Correspondingly, the advantages, limitations, and future prospects of these surface modification methods were discussed. This review provides an important guidance or tool for developing surface functionalized PUs in the fields of bioengineering and medical devices.

Genetic prediction of micronutrient levels and the risk of colorectal polyps: A mendelian randomization study.

OBJECTIVE: Previous epidemiological and experimental studies have yielded conflicting results regarding the influence of human micronutrient levels on the risk of colorectal polyps (CP). In our study, we conducted a two-sample Mendelian randomization (MR) investigation to probe the link between 13 human micronutrients (calcium, selenium, magnesium, phosphorus, folate, vitamins B-6, B-12, C, D, beta-carotene, iron, zinc, and copper) and the genetic susceptibility to CP. METHODS: Summary statistics for CP (n = 463,010) were obtained from pan-European genome-wide association studies, and instrumental variables for 13 micronutrients were screened from published genome-wide association studies (GWAS). After selecting suitable instrumental variables, we performed a two-sample MR study, deploying sensitivity analyses to judge heterogeneity and pleiotropy, using inverse variance weighted methods as our primary estimation tool. RESULTS: Our study identified that a genetic predisposition to elevated toenail and circulating selenium or serum ß-carotene concentrations lowers the risk of CP occurrence. However, no statistically significant association was observed between the other 11 micronutrients and the risk of CP. CONCLUSION: The study findings provide evidence that the micronutrient selenium and ß-carotene may confer protective effects against the development of CP.

Hemostasis-osteogenesis integrated Janus carboxymethyl chitin/hydroxyapatite porous membrane for bone defect repair.

Barrier membranes with osteogenesis are desirable for promoting bone repair. Janus membrane, which has a bilayered structure with different properties on each side, could meet the osteogenesis/barrier dual functions of guided bone regeneration. In this work, new biodegradable Janus carboxymethyl chitin membrane with asymmetric pore structure was prepared based on thermosensitive carboxymethyl chitin without using any crosslinkers. Nano-hydroxyapatites were cast on single-sided membrane. The obtained carboxymethyl chitin/nano-hydroxyapatite Janus membrane showed dual biofunctions: the dense layer of the Janus membrane could act as a barrier to prevent connective tissue cells from invading the bone defects, while the porous layer (with pore size 100-200 µm) containing nano-hydroxyapatite could guide bone regeneration. After implanted on the rat critical-sized calvarial defect 8 weeks, carboxymethyl chitin/nano-hydroxyapatite membrane showed the most newly formed bone tissue with the highest bone volume/total volume ratio (10.03 ± 1.81 %, analyzed by micro CT), which was significantly better than the commercial collagen membrane GTR® (5.05 ± 0.76 %). Meanwhile, this Janus membrane possessed good hemostatic ability. These results suggest a facile strategy to construct hemostasis-osteogenesis integrated Janus carboxymethyl chitin/hydroxyapatite membrane for guided bone regeneration.

Silver loaded biodegradable carboxymethyl chitin films with long-lasting antibacterial activity for infected wound healing.

Bacteria-related infections are one of the main causes of human skin infections, which are associated with the delay of wound healing and secondary complications. In this work, a series of novel biodegradable films based on thermosensitive carboxymethyl chitin were prepared without using any crosslinkers. All the carboxymethyl chitin films had good flexibility, high transparency, and appropriate water absorption capacity, and could provide a moist environment for wound healing. The silver ions (Ag+) were incorporated on the LTCF-5 film, which had the best mechanical strength (56.39 MPa in the dry state and 0.66 MPa in the wet state) among the carboxymethyl chitin films and was higher than those of the reported biodegradable dressings and commercially available dressings. Compared with the commercial hydrofiber dressing with silver (AQUACEL®), the composite film could provide slow and sustained release of Ag+ with good strength and biodegradability, and displayed excellent long-lasting antibacterial activity in vitro against both S. aureus and E. coli without obvious cytotoxicity, which still possessed good antibacterial activity with almost 100% bacteriostatic rates after soaking in phosphate buffered saline for 7 days. More importantly, the Ag+ loaded carboxymethyl chitin film could promote infected cutaneous wound healing in a S. aureus infected full-thickness cutaneous defect in vivo model because of its long-lasting antibacterial activity, good biocompatibility, exudate absorption and ability to maintain a moist environment. Thus Ag+ loaded carboxymethyl chitin films are excellent candidates for infected wound healing.

Biodegradable carboxymethyl chitin-based hemostatic sponges with high strength and shape memory for non-compressible hemorrhage.

Uncontrolled hemorrhage of deep, narrow and non-compressible perforating wounds is responsible for many trauma deaths. In this work, a novel biodegradable hemostatic sponge based on thermosensitive carboxymethyl chitin was prepared via simple cryo-regeneration process without using any crosslinkers. The collagen and polydopamine were added to further enhance mechanical and hemostatic properties of the sponge. All the carboxymethyl chitin based sponges showed high strength with excellent water/blood-triggered shape memory property, and the highest compressive fracture wet-strength could reach about 291.2 kPa, which was almost higher than those of many reported biodegradable hemostatic sponges pre-swelled in water. More importantly, the carboxymethyl chitin-collagen-polydopamine sponges displayed much better blood-clotting capacity and superior hemostasis performance than gauze and clinically used collagen sponge iRegene@ in vitro and in the rat liver perforating wound model. This study revealed a facile strategy to construct the effective carboxymethyl chitin based hemostatic sponges for the deep and non-compressible perforating wound.

Size-tunable and biodegradable thrombin-functionalized carboxymethyl chitin microspheres for endovascular embolization.

As a minimally invasive method, endovascular embolization has been an effective strategy for controlling bleeding and tumor treatment. Herein, carboxymethyl chitin embolic microspheres were prepared with the aqueous two-phase carboxymethyl chitin/polyethylene glycol system without using any crosslinking agents and thrombin-functionalized embolic microsphere named as Thr@CMCHm-30 was made after covalent introduction of thrombin. The size of the microspheres can be adjusted from 5 to 500 µm. The data of in vitro and in vivo tests indicated that these microspheres possessed good degradability and biocompatibility. Meanwhile, Thr@CMCHm-30 can significantly promote blood clotting and enhance the strength of the blood clots. More importantly, Thr@CMCHm-30 displayed better embolization effect than that of the commercial available Gelfoam Alicon® and polyvinyl alcohol-based embolic microspheres CalliSpheres® in rat femoral vein and rabbit ear artery embolization models. Therefore the size-tunable and biodegradable thrombin-functionalized carboxymethyl chitin microspheres Thr@CMCHm-30 possess great potential for effective hemostasis and endovascular embolization.

Injectable hydroxypropyl chitin hydrogels embedded with carboxymethyl chitin microspheres prepared via a solvent-free process for drug delivery.

Microspheres and injectable hydrogels derived from natural biopolymers have been extensively investigated as controlled local drug delivery systems. In this study, we prepared carboxymethyl chitin microspheres (CMCH-Ms) with a diameter of 10-100 µm through physical crosslinking by increasing temperature in an aqueous two-phase system without using organic solvents, surfactants and crosslinking agents. The stable microspheres keeping spherical shape with porous microstructure in different pH environments were embeded in thermosensitive hydroxypropyl chitin (HPCH) hydrogels. The morphology, gelation rate, swelling, rheological and mechanical properties, in vitro degradation and cytotoxicity, drug loading and drug release of the CMCH-Ms/HPCH gel scaffolds were examined. In vitro degradation and cytotoxicity test indicated that CMCH-Ms/HPCH gel scaffolds were biodegradable and non-cytotoxic. Moreover, no organic solvent was used in the preparation and drug loading process of CMCH-Ms/HPCH gel scaffold. Importantly, less burst drug release and long-term sustained-release from the CMCH-Ms/HPCH composite hydrogel was observed than those from only CMCH-Ms or HPCH hydrogel. Thus, the composite CMCH-Ms/HPCH hydrogel exhibited great potential application for loading different drugs and sustained drug release in controlled local drug delivery systems.

Degradable porous carboxymethyl chitin hemostatic microspheres.

Lethal hemorrhage could endanger lives. Although many hemostatic agents are commercially available with good clinical effect, it is necessary to develop novel hemostatic materials with high efficacy, biological safety, low cost, easily preparation and excellent biodegradability and biocompatibility. Here, novel biodegradable and uniform microspheres with regular spherical architecture and porous microstructure were prepared by thermosensitive carboxymethyl chitin (CMCH) with low substitution degree and low deacetylation through physical-crosslinking at high temperature without using any toxic crosslinkers. The obtained CMCH microspheres (CMCH-MS) were non-cytotoxic, low hemolytic potential and biodegradable in the presence of lysozyme. In vitro blood clotting evaluation indicated that the porous microsphere network structures and the hydrophilicity of the CMCH could promote hemostasis due to the quick blood absorption and local concentration of the coagulation factors for the CMCH-MS. The CMCH-MS showed much better hemorrhage control than negative control and traditional hemostatic chitosan, similar hemostatic performance as commercialized cross-linked starch microspheres in both rat tail and liver models. Thus, the new biodegradable porous CMCH-MS may hold great potential for hemorrhage control in medical treatment.

In-situ forming thermosensitive hydroxypropyl chitin-based hydrogel crosslinked by Diels-Alder reaction for three dimensional cell culture.

Injectable thermosensitive hydrogels crosslinked physically have been extensively studied as scaffolds in biomedical field, however, their low gel stability with weak strength limits their potential applications. Here, a novel thermosensitive furyl-modified hydroxypropyl chitin polymer was synthesized homogeneously in aqueous solution for developing injectable and dually crosslinked degradable hydrogel by integration of Diels-Alder click reaction using crosslinker maleimide-terminated PEG under physiological conditions. The dually crosslinked chitin-modified hydrogel showed much higher mechanical strength and slower biodegradation rate in contrast with the solely physically crosslinked thermosensitive hydroxypropyl chitin hydrogel. Cells encapsulated in the hydrogel displayed sustainable proliferation and good ability of self-assembling to form multicellular spheroids. In vivo investigation of the thermosensitive chitin-based dually crosslinked hydrogel showed favorable injectability, in-situ thermogelation and good biocompatibility. Thus the injectable, biodegradable and biocompatible dually crosslinked chitin-based hydrogel holds great potential for being applied in three dimensional cell culture and tissue repair.