Hemolysis Rate Research Articles

Glucose Oxidase-Loaded MnFe2O4 Nanoparticles for Hyperthermia and Cancer Starvation Therapy

Nanoparticle-mediated starvation therapy is a promising therapeutic approach for cancer treatment. Here, we report a novel therapeutic nanosystem (GOx@PEG-MnFe2O4) composed of glucose oxidase (GOx) loaded in polyethylene glycol (PEG) modified manganese ferrite (MnFe2O4) nanoparticles (NPs) for cancer starvation therapy. GOx catalyzes the oxidation of glucose to gluconic acid and hydrogen peroxide (H2O2) by consuming oxygen (O2) in an acidic environment. Meanwhile, NPs can catalyze the oxidation of H2O2 to generate O2, which, in turn, aids in the depletion of glucose and eliminate the hypoxia condition. Phase identification, crystal structure, and size of the NPs confirm the cubic spinel structure with an average crystallite size of 21 nm. NPs exhibit good magnetic susceptibility with a magnetization value of ∼75 emu/g at room temperature. Heating potentiality of the NPs with an obtained specific absorption rate (SAR) of 296 W/g proves the efficacy of NPs to act as a heating agent for cancer hyperthermia, which aid for a synergistic therapy combining magnetic hyperthermia with glucose oxidase-based starvation therapy. Fourier transform infrared spectroscopy and thermogravimetry analysis confirm the successful loading of GOx onto the PEG-MnFe2O4 nanosystem. The nanosystem exhibited ∼82% release of GOx in the cancer cell-mimicking environment in an applied magnetic field which is around 1.8 times higher than that in the normal cell-mimicking environment. In vitro assessment against HeLa and Saos-2 cancer cell lines demonstrated anticancer activity and exhibited reduced hemolysis rates. Furthermore, the in vitro results suggested that the NPs are biocompatible and have potential hyperthermic ability. The designed nanosystem is capable of effectuating the tumoricidal effect via cancer starvation therapy.

3D-Structured and Blood-Contact-Safe Graphene Materials

Graphene is a promising material that may be potentially used in biomedical applications, mainly for drug delivery applications. In our study, we propose an inexpensive 3D graphene preparation method by wet chemical exfoliation. The morphology of the graphene was studied by SEM and HRTEM. Moreover, the volumetric elemental composition (C, N, and H) of the materials was analyzed, and Raman spectra of prepared graphene samples were obtained. X-ray photoelectron spectroscopy, relevant isotherms, and specific surface area were measured. Survey spectra and micropore volume calculations were made. In addition, the antioxidant activity and hemolysis rate in contact with blood were determined. Activity against free radicals of graphene samples before and after thermal modification was tested using the DPPH method. The RSA of the material increased after graphene modification, which suggests that antioxidant properties were improved. All tested graphene samples caused hemolysis in the range of 0.28-0.64%. The results showed that all tested 3D graphene samples might be classified as nonhemolytic.

The potential role of vitamin E in patients with glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis.

As an antioxidant, vitamin E (VitE) may benefit the erythrocytes by protecting glutathione from oxidation by free radicals and peroxide-generating processes. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines when reporting this systematic review. We searched 6 electronic databases (PubMed, Scopus, Web of Science, and Cochrane Library) until May 8, 2022. We included all relevant studies. According to the study design, the Cochrane assessment tool (Risk of Bias 2), Risk Of Bias In Non-randomized Studies - of Interventions checklists, and National Institutes of Health tools were used to assess the risk of bias.Continuous data were pooled as a mean difference (MD) with a relative 95% confidence interval. The protocol was registered on PROSPERO (CRD42022333848). Six studies were included in the meta-analysis with a total of 181 patients. Compared with the control group, VitE significantly improved the hemoglobin level for chronic hemolysis (MD = 2.72 g/dL, P < .0001) and for acute hemolysis (MD = 1.18 g/dL, P < .0001). It also decreased the reticulocyte level for chronic hemolysis (MD = -1.39 P < .0001) and for acute hemolysis (MD = -1.42%, P < .0001). For before and after studies, the use of VitE significantly improved the level of packed cell volume (MD = 0.56%, P < .00001), red blood cell half-life (MD = 2.19 days, P < .0001), and decreased the reticulocytes level (MD = -1.41%, P < .00001). Among patients with glucose-6-phosphate dehydrogenase deficiency, VitE might provide benefits such as increasing the hemoglobin, packed cell volume levels, red blood cell half-life, and decreasing the reticulocyte level, so reducing hemolysis. Further high-quality, well-designed randomized controlled trials are recommended.

Sustainable wheat gluten foams with self-expansion and water/blood-triggered shape recovery.

A cheap and easily obtainable wheat gluten (WG) was used to fabricate bio-foams via a simple method of stirring, heating, and lyophilization. The foam possesses a 3D layered porous structure with interconnected channels, and the biofoam has excellent mechanical properties through glycerol plasticization and glutaraldehyde (GA) cross-linking. The water absorption and volume expansion rate can reach 793.67 ∼ 918.45% and 201.47 ∼ 239.53% respectively. In dry state, the foams had good compression resilience, and can basically recover its original shape after withstanding 60% compression strain for about 7h. In wet state, they can withstand 10 cycles of compression test, and had good compressive resilience and durability; they also had fast liquid-triggered shape recovery performance, of which the foams can reabsorb liquid, expand, and recover its original shape within 40seconds after withstanding 80% compression strain. In addition, The hemolysis rates of red blood cells treated with 1, 3, and 5mg/mL of 14WG-20g-5GA foam suspension were 0.53 ± 0.12%, 2.12 ± 0.34%, and 3.97 ± 0.21%, respectively, all of which were below the permissible range for biological materials (<5%). The above-mentioned advantages made the sustainable foams be potentially useful for medical dressings, especially for the treatment of non-compressible haemorrhaging, which offered a new field of application for WG protein and its added value was also increased obviously.

Research of Dynamic Corrosion Behavior, Microstructure, and Biocompatibility of Mg–Zn–Ca–Zr Alloys in Simulated Body Fluid Solution Induced by Zn Element Addition

Herein, the effect of Zn (2,3,4 and 5 wt%) addition on the microstructure, corrosion behavior, and biocompatibility of Mg‐xZn‐0.5Ca‐0.4Zr alloys is discussed by micromorphology, immersion/electrochemical, and cytotoxicity experiments. The results reveal that all as‐cast samples with a duplex morphology consist of Mg7Zn3 phase and α‐Mg matrix. With the addition of Zn element, the quantities of Mg7Zn3 phase increase gradually; while its micromorphology obviously changes from dot‐like to network shape, the average grain size decreases gradually. In addition, corrosion mechanism demonstrates that all as‐cast alloys suffer from microgalvanic corrosion between eutectic Mg7Zn3 and α‐Mg substrate due to potential difference of |ΔE| = 180 mV. However, the strip‐shape Mg7Zn3 contained in the Mg–4Zn–0.5Ca–0.4Zr alloy and compared with dot‐like\network shape phase can effectively hinder the spreading of corrosion from one grain to another, which causes Mg–4Zn–0.5Ca–0.4Zr to exhibit superior corrosion resistance. In addition, the biocompatibility conducted by methyl‐thiazolyl‐tetrazolium method via L929 cells reveals that as‐cast Mg–4Zn–0.5Ca–0.4Zr alloy is confirmed with low hemolysis rate (H% = 2.5%) and excellent proliferation capability (P% &gt; 100%), which suggest that Mg–4Zn–0.5Ca–0.4Zr may be a good candidate for implant application.

Preparation of hyaluronic acid-loaded Harmine polymeric micelles and in vitro effect anti-breast cancer

AimsTo prepare hyaluronic acid-loaded Harmine polymeric micelles with CD44 targeting properties and to investigate their anti-breast cancer effects in vitro. MethodsThe carboxyl group on hyaluronic acid is coupled to the amino group on 3,5-bis(trifluoromethyl)benzylamine by an amidation reaction. And the polymeric micelles self-assemble to encapsulate the Harmine in a hydrophobic core, characterized the polymer micelles by IR, 19F-NMR, Malvern particle sizing, release, hemolysis, and other experiments. Used CD44-positive MDA-MB-231 cells and CD44-negative MCF-7 cells as tumor models. The effect of polymer micelles on breast cancer cells in vitro by cytotoxicity assay, confocal, and flow cytometry. ResultsThe prepared polymer micelles had a uniform particle size of about 200 nm, good dispersion, PDI < 0.3, encapsulation rate up to 87%, drug loading of 4.12±0.03%, and negative charge. Hyaluronidase has a good enzymatic effect on polymeric micelles, with a hemolysis rate of less than 1%. It showed some dose-dependent toxicity to both MDA-MB-231 and MCF-7, with increased uptake of polymer micelles by CD44-positive MDA-MB-231 compared to CD44-negative MCF-7 cells and significant effects of polymer micelles on apoptosis and cycling in both cell types. These results suggest that the hyaluronic acid-loaded Harmine polymer micelles designed in this study are effective in killing breast cancer cells while at the same time reducing the toxicity of Harmine and improving its slow-release targeting.

Nanocellulose aerogels from banana pseudo-stem as a wound dressing

Wound dressings with natural antimicrobial, moisturizing and swelling properties have received increasing attention. However, many natural materials used as wound dressings require chemical cross-linking agents or acidic and alkaline environments and have problems such as poor stability and uneven distribution. In this study, banana nanocellulose (BCNF) with a diameter of less than 70 nm was extracted from banana pseudo-stem through benzyl alcohol extraction, sodium chlorite bleaching, potassium hydroxide alkaline treating, and ultrasonic crushing treatment. There was an addition of konjac glucomannan (KGM) to 0.8 wt% nanocellulose suspension and freeze-drying to form composite aerogel (BCNK) by freeze-drying. Different ratios of BCNF and KGM were used to regulate the performance of aerogels such as swelling, water retention, water vapor transmission rate, and mechanical property. It was evident that the aerogel with an 8/2 mass ratio of BCNF to KGM (BCNK2) exhibited better performance, with a 2981% swelling rate, 97.71% porosity, and 810 g·m−2·d−1 water vapor transmission rate, and also showed the applicable mechanical properties. According to the results of antibacterial and biocompatibility, the composite aerogel had commendable inhibitory effects on E. coli and S. aureus. The hemolysis rate of BCNK2 was 3.38% and the cell survival rate was over 90%, which proved that BCNK2 had good hemolysis and no cytotoxicity. Therefore, the nanocellulose composite aerogel prepared from banana pseudo-stem has the potential to be applied to wound dressings.

Increased hemolysis rate in plasma tubes after implementation of a fully automated sample delivery and acceptance system

Abstract Objectives Automated sample delivery and laboratory acceptance systems (PTAS) may influence the hemolysis rate of blood samples due to g-forces, abrupt acceleration, and rapid deceleration. However, quantitative data regarding the rate of hemolysis in PTAS is limited. To fill this void, the effect of a pneumatic tube in combination with an acceptance system (PTAS) on the hemolysis rate was investigated in this study. Methods Lithium heparin plasma tubes were transported from different clinical departments to the hospital’s laboratory (a) by employees or (b) with an automated PTAS and analyzed for the presence of hemolysis based on a hemolysis index (HI) of &gt;25. Hemolysis indices of 68.513 samples were retrieved from the laboratory information system before and after installation of the PTAS and were subjected to statistical analysis. Results A total of 32.614 samples were transported by employees, of which 3.815 samples (11.70%) were hemolytic, and 9.441 out of 35.899 samples delivered by PTAS (26.30%) were hemolytic. After the implementation of the PTAS, hemolysis rates increased in all departments. Conclusions Automated PTAS are associated with increased hemolysis rates. This has implications for routine patient management and should be considered for the transportation of samples used for the determination of hemolysis-sensitive laboratory parameters.

Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PLpro Protein

Recent studies have shown that the peptide [des-Cys11,Lys12,Lys13-(p-BthTX-I)2K] (p-Bth) is a p-BthTX-I analog that shows enhanced antimicrobial activity, stability and hemolytic activity, and is easy to obtain compared to the wild-type sequence. This molecule also inhibits SARS-CoV-2 viral infection in Vero cells, acting on SARS-CoV-2 PLpro enzymatic activity. Thus, the present study aimed to assess the effects of structural modifications to p-Bth, such as dimerization, dendrimerization and chirality, on the antibacterial activity and inhibitory properties of PLpro. The results showed that the dimerization or dendrimerization of p-Bth was essential for antibacterial activity, as the monomeric structure led to a total loss of, or significant reduction in, bacterial activities. The dimers and tetramers obtained using branched lysine proved to be prominent compounds with antibacterial activity against Gram-positive and Gram-negative bacteria. In addition, hemolysis rates were below 10% at the corresponding concentrations. Conversely, the inhibitory activity of the PLpro of SARS-CoV-2 was similar in the monomeric, dimeric and tetrameric forms of p-Bth. Our findings indicate the importance of the dimerization and dendrimerization of this important class of antimicrobial peptides, which shows great potential for antimicrobial and antiviral drug-discovery campaigns.

Evaluation of the efficacy of the antimicrobial peptide HJH-3 in chickens infected with Salmonella Pullorum.

As a promising substitute for antibiotics, increasing attention has been given to the clinical application of antimicrobial peptides (AMPs). In this study, the mode of action of the HJH-3 against Salmonella Pullorum was investigated. The structure and properties of HJH-3 were examined in silico, and minimum inhibitory concentrations (MICs) were determined to evaluate its antimicrobial spectrum. The time-kill kinetics of HJH-3 was determined. The hemolytic activity of HJH-3 was determined by measuring the hemoglobin ultraviolet absorption value, and the cytotoxicity was determined using a CCK-8 kit. The protective effect of HJH-3 on chickens infected with S. Pullorum was evaluated in vivo. The results demonstrated that HJH-3 exhibited strong antibacterial activity against Gram-negative pathogens at MIC values of 1.5625-25 μg/mL and against Gram-positive pathogens at MIC values of 25-50 μg/mL. HJH-3 also showed activity against the Candida albicans (100 μg/mL) and Bacillus subtilis (6.25-12.5 μg/mL). HJH-3 at 100 μg/mL completely killed S. Pullorum after co-incubation for 6 h. Likewise, the hemolysis rate of CRBCs treated with 100 μg/mL HJH-3 (7.31%) was lower than that of CRBCs treated with 100 μg/mL pexiganan (40.43%). Although the hemolysis rate of CRBCs treated with 400 μg/mL HJH-3 was increased to 13.37%, it was much lower than that of 400 μg/mL pexiganan (57.27%). In regards to cytotoxicity, HJH-3 had almost no-effect on the CEF proliferation, pexiganan decreased CEFs proliferation from 56.93 to 31.00% when increasing the concentration from 50 to 200 μg/mL. In a chicken infection model, the results showed that the antibiotic prevention and HJH-3 prevention groups exhibited the best treatment effect, with the chickens being protected from the lethal dose of S. Pullorum, a decreased number of bacteria in the blood and spleen, and less pathological changes in intestinal segments. The prevention of infection by HJH-3 was similar to that by Ampicillin; the effect of treatment after infection was lower than that of treatment before infection, and the survival rate of infected chicks treated with HJH-3 was 70%, which was still higher than that of the infected chickens. These results suggest that HJH-3 has good clinical application potential and can be used as a substitute for antibiotics for the prevention and treatment of S. Pullorum infection.

Metal-polyphenol polymer modified polydopamine for chemo-photothermal therapy.

Chemotherapy combined with photothermal therapy (PTT) is a new way to improve the curative effect of cancer treatment. Here, we developed a multifunctional nanoparticle, namely PTX@mPDA@Fe-GA with the loading of a chemotherapeutic drug paclitaxel (PTX) for targeted and synergistic chemotherapy/photothermal therapy in lung cancer. Fe-gallic acid (Fe-GA) was coated on the surface of mesoporous polydopamine (mPDA) nanoparticles, and then the PTX was placed in the mesopores. The drug release of the loaded PTX exhibited pH- and thermal-dual responsive manner. Both mPDA and Fe-GA have high photothermal conversion ability and play a role in photothermal therapy. In addition, the results revealed that mPDA@Fe-GA had excellent biocompatibility and low hemolysis rate. The PTX-loaded mPDA@Fe-GA not only has excellent killing effect on lung cancer cells (A549) in vitro, but also can significantly suppress the growth of A549 subcutaneous tumor in nude mice. In a nutshell, the developed multifunctional nanoparticles integrate photothermal therapy and efficient chemotherapeutic drug delivery, providing new therapeutic ideas in the fight against lung cancer.

Electrospinning polycaprolactone/collagen fiber coatings for enhancing the corrosion resistance and biocompatibility of AZ31 Mg alloys

Magnesium (Mg) alloy is widely studied as a potential biodegradable implant material in clinical orthopedics. However, its uncontrollable corrosion rate under physiological conditions has severely limited its development. To enhance the corrosion resistance and biocompatibility of AZ31 Mg alloys substrate, the polycaprolactone/collagen/cerium-hydroxyapatite (PCL/Col/Ce-HA) fiber coating is prepared by employing the electrospinning technique. The scanning electron microscope reveals that the PCL/Col/Ce-HA fiber coating with 5 wt% of Ce-HA exhibits the densest surface with a uniform fiber size of 396 nm, which provides a firm physical barrier against the corrosive ions. Furthermore, the enhanced adhesion strength of the PCL/Col/Ce-HA fiber coating will prevent the coating from falling off from the Mg substrate during the long-term immersion periods, and therefore ensures their durability. Electrochemical tests indicate that the annual corrosion rate of PCL/Col/Ce-HA fiber coating with 5 wt% Ce-HA is almost 30 times lower than the bare AZ31 Mg alloy. The lowest hydrogen evolution volume and relatively stable pH variations of the solution also confirm their effective protective ability. In addition, the cell assay indicates that the PCL/Col/Ce-HA fiber coating is beneficial for cell adhesion and growth, reflecting its excellent cell biocompatibility. The lowest hemolysis rate (2.72%) of PCL/Col/Ce-HA fiber coating also meets the biomedical material application requirements.

Electrical-responsive biocompatible coatings for highly corrosion-resistance and self-healing performance on AZ31 Mg alloy

An electrically stimulated smart 8-hydroxyquinoline loaded poly(3,4-ethylenedioxythiophene) (8-HQ@PEDOT) nanocapsules are fabricated via emulsion polymerization. SEM and TEM images indicate that the 8-HQ@PEDOT nanocapsules display a hollow nanosphere structure with an average diameter of 300–500 nm. TGA results confirm the loading ratio of 8-HQ inhibitors in 8-HQ@PEDOT nanocapsules is approximately at about 8.2 %. Furthermore, increased concentrations of the 8-HQ inhibitors are achieved after applying higher negative voltages, reflecting its evident electrical-responsive features. Afterward, 8-HQ@PEDOT nanocapsules are incorporated into the polylactic acid (PLA) coatings and deposited on the AZ31 Mg alloy surface. The corrosion resistance and self-healing performance of the PDA/8-HQ@PEDOT/PLA coatings are explored by electrochemistry tests. The EIS tests and hydrogen evolution test indicate that the PDA/8-HQ@PEDOT/PLA coatings show enhanced corrosion protective performance and remarkable self-healing ability during the immersion period. In addition, a larger number of MG-63 cells can survive on the coating surface and the hemolysis rate value of 2.68 % confirms their indicating the excellent biocompatibility of PDA/8-HQ@PEDOT/PLA coatings. The designed PDA/8-HQ@PEDOT/PLA coatings possessed remarkable anti-corrosive, self-healing and biocompatibility, which has great potential in the bio-implant material applications field.

Preparation and surface modification of ultrahigh throughput tannic acid coblended polyethersulfone ultrafiltration membranes for hemodialysis

AbstractLow dialysis and blood incompatibility efficiency are key issues to be addressed for polymeric hemodialysis membranes. To improve the comprehensive performance of hemodialysis membranes, polyethersulfone (PES)/tannic acid (TA) coblended ultrafiltration membranes were prepared and modified with a heparin‐like functionalized TA coating. The coblended TA improved the pore structure of the PES ultrafiltration membrane. And it could also undergo π‐π conjugation with the heparin‐like functionalized TA in the modified solution, resulting in a greater abundance of modified groups loaded on the membrane surface and pores close to the surface. The modified coating further improved the membrane performance. The physicochemical properties, solute filtration, and blood compatibility properties of the membrane were tested. The effect of TA on the pore structure of the membrane and the presence of modified layers were demonstrated by morphological and chemical structure analyses. The final modified membrane had an ultrahigh water flux (1053 L/m2·h), improved dialysis performance (BSA retention &gt;99%, Lysozyme clearance &gt;30% and Urea clearance &gt;90%), and excellent hemocompatibility (The hemolysis rate was 1.31%, and APTT, PT, and TT values were increased by 40.8%, 74.2%, and 85.9%, respectively). This study shows that TA has great potential for improving the pore structure of polymeric membranes.

Comparison of a Novel Thin-Walled 25-gauge Needle Push Button Blood Collection Set to a Standard 23-gauge Needle in a Cancer Patient Population.

Phlebotomy can be an uncomfortable and even painful experience that increases in likelihood in patients who require frequent blood draws, such as those with cancer. The 25-gauge BD Vacutainer® UltraTouch™ Push Button Blood Collection Set has a smaller outer bore needle size and unique bevel configuration, which in theory should reduce pain associated with phlebotomy. Smaller needles typically cause less pain, however, they have a higher incidence of compromising the specimen integrity. Innovative engineering allows this particular needle to maintain a larger inner bore size similar to a standard 23-gauge needle. This study compares pain and specimen integrity between this novel device and a standard 23-gauge needle. Two cohorts of 190 patients each had phlebotomy performed with either needle. Pain experienced was assessed by patient surveys, rating pain from 0 (low) to 10 (high). Sample integrity was assessed by determining the hemolysis index (Abbott Architect c8000). No statistically significant difference in median pain scores was observed between the 2 cohorts, P-value: 0.068. The 23-gauge cohort more frequently reported 3+ pain than the 25-gauge cohort, 14/190 vs 5/190. Pain scoring 1 and 2 was more frequent in the 25-gauge cohort, 84/190 vs 54/190. Pain scores of 0 were more frequent in the 23-gauge cohort, 122/190 vs 101/190. This stratification is statistically significant, P-value: 0.003. The 25-gauge needle showed no increase in hemolysis rates, P-value: 0.5. Sample integrity was identical between both needles. The 25-gauge needle resulted in less 3+ pain, while pain scoring 1 and 2 was more frequent in the 25-gauge cohort.

A Celastrol Drug Delivery System Based on PEG Derivatives: The Structural Effects of Nanocarriers.

The therapeutic efficacy of nanoscale drug delivery systems is related to particle size, zeta potential, morphology, and other physicochemical properties. The structure and composition of nanocarriers may affect their physicochemical properties. To systematically evaluate these characteristics, three analogues, namely polyethylene glycol (PEG), PEG-conjugated octadecylamine (PEG-C18), and tri(ethylene glycol) (TEG), were explored as nanocarriers to entrap celastrol (CSL) via the injection-combined dialysis method. CSL nanoparticles were successfully prepared as orange milky solutions, which revealed a similar particle size of approximately 120 nm, with narrow distribution and a negative zeta potential of -20 mV. All these CSL nanoparticles exhibited good storage stability and media stability but presented different drug-loading capacities (DLCs), release profiles, cytotoxicity, and hemolytic activity. For DLCs, PEG-C18/CSL exhibited better CSL entrapment capacity. Regarding the release profiles, TEG/CSL showed the lowest release rate, PEG-C18/CSL presented a moderate release rate, and PEG/CSL exhibited a relatively fast release rate. Based on the different release rates, PEG-C18/CSL and TEG/CSL showed higher degrees of cytotoxicity than PEG/CSL. Furthermore, TEG/CSL showed the lowest membrane toxicity, and its hemolytic rate was below 20%. These results suggest that the structural effects of nanocarriers can affect the interactions between nanocarriers and drugs, resulting in different release profiles and antitumor activity.

A polysaccharide/chitin hydrogel wound dressing from a Periplanattica americana residue: coagulation, antioxidant activity, and wound healing properties

Pharmaceuticals derived from the raw materials of Periplanattica americana have been applied for wound healing, liver disease treatment, and antitumor therapy. However, the resulting residues of P. americana have not been well exploited. We found that P. americana residues comprised high amounts of chitin (PC) and polysaccharides (PAP) exhibit good biological activity. Compared to shrimp-derived chitin, PC has a smaller molecular weight (Mv), lower crystallinity, and looser molecular structure, demonstrating stronger antioxidant activity and degradability. After adding the PAP, the PC solution rapidly lost fluidity and formed a hydrogel (P/PCGEL) that had antioxidation, biodegradability, and injectability properties and exhibited rapid coagulation, good water absorption and retention, and a low hemolysis rate (HR). In vivo studies reported that the P/PCGEL reduced edema during burns, accelerated collagen synthesis and deposition, reduced reactive oxygen species (ROS) levels, and increased superoxide dismutase (SOD) levels, thereby reducing the inflammatory response, avoiding oxidative stress, and effectively promoting wound healing. Furthermore, the P/PCGEL demonstrated good biocompatibility, rapid biodegradation, and injectability, thereby reducing the risk of trauma and infection engendered by repeated wound opening and dressing changes. These properties also demonstrated the potential application for this hydrogel in preparing injectable hydrogel excipients. Hence, this study provided a hydrogel-formed wound dressing comprising pure natural ingredients and offering convenient administration, economic availability, and strong tissue repair ability.

Preparation of fully bio-based multilayers composed of heparin-like carboxymethylcellulose sodium and chitosan to functionalize poly (l-lactic acid) film for cardiovascular implant applications

In this study, heparin-like polysaccharides were successfully produced by sulfation of carboxymethylcellulose sodium, then a fully biobased bilayer composed of sulfated carboxymethylcellulose sodium (SCMC) and chitosan (CS) was composited on the surface of Poly (L-lactic acid) (PLA) through layer-by-layer (LBL) assembly for the potential blood-contact application such as bioresorbable vascular scaffold. The preliminary structure and bioactivity of SCMC with different degree of sulfation were investigated, and the SCMC with best performance was selected. The surface chemical compositions, morphologies and wettability of SCMC/CS multilayer-modified PLA films were researched by X-ray photoelectron spectrometer, scanning electron microscopy and water contact angle meter. A series of anticoagulation tests of SCMC/CS multilayer-modified PLA films were performed. In term of (SCMC/CS)15 multilayer-modified PLA film, the protein adsorption and plate adhesion decreased by 44.6 % and 71.5 %, respectively, the activated partial thromboplastin time prolonged by 11.9 times and thrombin time exceed 300 s, the contact activation and hemolysis rate significantly reduced compared with unmodified PLA film. Besides, this modified PLA films performed good cytocompatibility to L929 fibroblast cells, excellent anti-inflammatory and antibacterial abilities. In conclusion, the multifunctional SCMC/CS multilayer-modified PLA films with hemocompatibility, cytocompatibility, anti-inflammatory and antibacterial properties may have promising potential in future clinical applications.

Electrospinning of peanut protein isolate/poly-L-lactic acid nanofibers containing tetracycline hydrochloride for wound healing

In the present study, we explored the feasibility of using electrospinning technology to prepare tetracycline-hydrochloride (TCH)-containing peanut protein isolate/poly-L-lactic acid (TCH/PPI/PLLA) nanofiber membranes as a new type of wound dressing. PPI was prepared using the alkali-dissolved acid precipitation method, and PPI/PLLA nanofibers containing TCH at mass loadings of 5%, 10%, and 15% were prepared by electrospinning. The resultant nanofibers were characterized by scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and comprehensive thermal analysis. Furthermore, the wettability, mechanical properties, and drug release efficacy of the TCH/PPI/PLLA nanofibers were evaluated, and their effect on Staphylococcus aureus and mouse skin fibroblasts were investigated. A mouse-skin wound model was established to assess the healing effect of TCH/PPI/PLLA nanofibers. The results revealed that TCH exists in the nanofibers in an amorphous state, and that the addition of TCH has no observable effect on the morphology of the nanofiber membrane. As the TCH content increases, the fiber diameter decreases, while the mechanical strength and wettability of the membranes increase. TCH/PPI/PLLA composite nanofibers provide a significant initial release of TCH, and the release mechanism of TCH appears to be Fick's diffusion. The hemolysis rates of the electrospun PLLA nanofibers, PPI/PLLA composite nanofibers, and drug-loaded PPI/PLLA nanofibers are all below 5%. TCH retains its anticoagulant effect when composited with the PPI/PLLA composite nanofibers and exhibits low toxicity to cells. The PPI/PLLA nanofiber membrane loaded with TCH has an inhibitory effect on S. aureus and E. coli，and promotes skin-wound healing in mice. Therefore, TCH/PPI/PLLA nanofiber membranes prepared by electrospinning technology show promise as a next-generation wound dressing material.

Multifunctional nanoparticle-VEGF modification for tissue-engineered vascular graft to promote sustained anti-thrombosis and rapid endothelialization.

Purpose: The absence of a complete endothelial cell layer is a well-recognized reason leading to small-diameter tissue-engineered vascular graft failure. Here we reported a multifunctional system consisting of chitosan (CS), Arg-Glu-Asp-Val (REDV) peptide, heparin, and vascular endothelial growth factor (VEGF) to achieve sustained anti-thrombosis and rapid endothelialization for decellularized and photo-oxidized bovine internal mammary arteries (DP-BIMA). Methods: CS-REDV copolymers were synthesized via a transglutaminase (TGase) catalyzed reaction. CS-REDV-Hep nanoparticles were formed by electrostatic self-assembly and loaded on the DP-BIMA. The quantification of released heparin and vascular endothelial growth factor was detected. Hemolysis rate, platelets adhesion, endothelial cell (EC) adhesion and proliferation, and MTT assay were performed in vitro. The grafts were then tested in a rabbit abdominal aorta interposition model for 3months. The patency rates were calculated and the ECs regeneration was investigated by immunofluorescence staining of CD31, CD144, and eNOS antibodies. Results: The nanoparticle-VEGF system (particle size: 61.8 ± 18.3nm, zeta-potential: +13.2mV, PDI: .108) showed a sustained and controlled release of heparin and VEGF for as long as 1month and exhibited good biocompatibility, a lower affinity for platelets, and a higher affinity for ECs in vitro. The nanoparticle-VEGF immobilized BIMA achieved 100% and 83.3% patency in a rabbit abdominal interposition model during 1 and 3months, respectively, without any thrombogenicity and showed CD31, CD144, eNOS positive cell adhesion as early as 1day. After 3months, CD31, CD144, and eNOS positive cells covered almost the whole luminal surface of the grafts. Conclusion: The results demonstrated that the multifunctional nanoparticle-VEGF system can enhance the anti-thrombosis property and promote rapid endothelialization of small-diameter tissue-engineered vascular grafts. Utilizing nanoparticles to combine different kinds of biomolecules is an appropriate technology to improve the long-term patency of small-diameter tissue-engineered vascular grafts.