A dual-gene panel of two fragments of methylated IRF4 and one of ZEB2 in plasma cell-free DNA for gastric cancer detection.

Early detection is crucial for increasing the survival rate of gastric cancer (GC). We aimed to identify a methylated cell-free DNA (cfDNA) marker panel for detecting GC. The differentially methylated CpGs (DMCs) were selected from datasets of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The selected DMCs were validated and further selected in tissue samples (40 gastric cancer and 36 healthy white blood cell samples) and in a quarter sample volume of plasma samples (37 gastric cancer, 12 benign gastric disease, and 43 healthy individuals). The marker combination selected was then evaluated in a normal sample volume of plasma samples (35 gastric cancer, 39 control diseases, and 40 healthy individuals) using real-time methylation-specific PCR (MSP). The analysis of the results compared methods based on 2-ΔΔCt values and Ct values. In the results, 30 DMCs were selected through bioinformatics methods, and then 5 were selected for biological validation. The marker combination of two fragments of IRF4 (IRF4-1 and IRF4-2) and one of ZEB2 was selected due to its good performance. The Ct-based method was selected for its good results and practical advantages. The assay, IRF4-1 and IRF4-2 in one fluorescence channel and ZEB2 in another, obtained 74.3% sensitivity for the GC group at any stage, at 92.4% specificity. In conclusion, the panel of IRF4 and ZEB2 in plasma cfDNA demonstrates good diagnostic performance and application potential in clinical settings.

Plasma methylated GNB4 and Riplet as a novel dual-marker panel for the detection of hepatocellular carcinoma.

Early detection of hepatocellular carcinoma (HCC) can greatly improve the survival rate of patients. We aimed to develop a novel marker panel based on cell-free DNA (cfDNA) methylation for the detection of HCC. The differentially methylated CpG sites (DMCs) specific for HCC blood diagnosis were selected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, then validated by the whole genome bisulphite sequencing (WGBS) of 12 paired HCC and paracancerous tissues. The clinical performance of the panel was evaluated using tissue samples [32 HCC, chronic liver disease (CLD), and healthy individuals] and plasma cohorts (173 HCC, 199 CLD, and 98 healthy individuals). The combination of G protein subunit beta 4 (GNB4) and Riplet had the optimal area under the curve (AUC) in seven candidates through TCGA, GEO, and WGBS analyses. In tissue validation, the GNB4 and Riplet showed an AUC of 100% with a sensitivity and specificity of 100% for detecting any-stage HCC. In plasma, it demonstrated a high sensitivity of 84.39% at 91.92% specificity, with an AUC of 92.51% for detecting any-stage HCC. The dual-marker panel had a higher sensitivity of 78.26% for stage I HCC than alpha-fetoprotein (AFP) of 47.83%, and a high sensitivity of 70.27% for detecting a single tumour (size ≤3 cm). In conclusion, we developed a novel dual-marker panel that demonstrates high accuracy in detecting HCC, surpassing the performance of AFP testing.

Strategy to combat biofilms: a focus on biofilm dispersal enzymes.

Bacterial biofilms, which consist of three-dimensional extracellular polymeric substance (EPS), not only function as signaling networks, provide nutritional support, and facilitate surface adhesion, but also serve as a protective shield for the residing bacterial inhabitants against external stress, such as antibiotics, antimicrobials, and host immune responses. Biofilm-associated infections account for 65-80% of all human microbial infections that lead to serious mortality and morbidity. Tremendous effort has been spent to address the problem by developing biofilm-dispersing agents to discharge colonized microbial cells to a more vulnerable planktonic state. Here, we discuss the recent progress of enzymatic eradicating strategies against medical biofilms, with a focus on dispersal mechanisms. Particularly, we review three enzyme classes that have been extensively investigated, namely glycoside hydrolases, proteases, and deoxyribonucleases.

Composite Hydrogel Conduit Incorporated with Platelet-Rich Plasma Improved the Regenerative Microenvironment for Peripheral Nerve Repair.

Peripheral nerve regeneration and functional recovery remain major challenges in clinical practice. Nerve guidance conduits (NGCs) which can regulate the regenerative microenvironment are beneficial for peripheral nerve repair. Platelet-rich plasma (PRP) can secrete multiple growth factors to regulate the regenerative microenvironment. However, current administration methods of PRP are rapidly activated followed by the burst release of growth factors, causing low therapeutic efficiency in vivo. To overcome these disadvantages, a composite nerve conduit was fabricated by incorporating PRP into a gelatin methacrylate (GelMA) and sodium alginate (SA) hydrogel. The GelMA/SA-3/PRP-20 NGCs possess optimal mechanical properties, degradation rate, and superior biological performance. Importantly, GelMA/SA-3/PRP-20 NGCs achieved the sustained release of two major growth factors (VEGF-A, PDGF-BB) from PRP. Moreover, the GelMA/SA-3/PRP-20 NGCs significantly promoted the migration of Schwann cells and the neovascularization of endothelial cells in vitro. While bridging 10 mm rat sciatic nerve defects, the GelMA/SA-3/PRP-20 NGCs promoted axonal regeneration and functional recovery of peripheral nerves. Therefore, the GelMA/SA-3/PRP-20 NGCs could regulate the regenerative microenvironment by sustained release of growth factors from PRP and shed new light on the clinical application of PRP in peripheral nerve repair.

Dual AuNPs detecting probe enhanced the NanoSPR effect for the high-throughput detection of the cancer microRNA21 biomarker.

The microRNA21 (miR-21), a specific tumor biomarker, is crucial for the diagnosis of several cancer types, and investigation of its overexpression pattern is important for cancer diagnosis. Herein, we report a low-cost, rapid, ultrasensitive, and convenient biosensing strategy for the detection of miR-21 using a nanoplasmonic array chip coupled with gold nanoparticles (AuNPs). This sensing platform combines the surface plasmon resonance effect of nanoplasmonics (NanoSPR) and the localized surface plasmon resonance (LSPR) effect, which allows the real-time monitoring of the subtle optical density (OD) changes caused by the variations in the dielectric constant in the process of the hybridization of the target miRNA. Using this method, the miRNA achieves a broad detection range from 100 aM to 1 µM, and with a limit of detection (LoD) of 1.85 aM. Furthermore, this assay also has a single-base resolution to discriminate the highly homologous miRNAs. More importantly, this platform has high throughput characteristics (96 samples can be detected simultaneously). This strategy exhibits more than 86.5 times enhancement in terms of sensitivity compared to that of traditional biosensors.

Fabrication of cellulose/rectorite composite films for sustainable packaging.

In order to reduce the environmental pollution caused by plastic packaging, the development of biodegradable high-performance packaging materials has become a research hotspot. Cellulose is a promising food packaging material, but it usually lacks sufficient ultraviolet (UV) shielding property and mechanical strength. In this work, rectorite microplates were incorporated into the cellulose matrix by a facile blending method to fabricate the composite films. The structure and properties of the composite films were characterized by FT-IR, X-ray diffraction, scanning electron microscopy, UV-vis and mechanical properties test etc. The results indicated that rectorite microplates were uniformly distributed in the cellulose matrix. The blocking percentages for UVA and UVB for the cellulose/rectorite composite film with 14 wt% rectorite content (RCRF-14) could reach as high as 97.8 % and 96.0 %, respectively, showing a good UV shielding property. Meanwhile, the addition of rectorite obviously improved the mechanical properties and decreased the water vapor and oxygen permeabilities of the cellulose film, showing a potential application as a sustainable food packaging material.

Genome-wide methylation profiling identify hypermethylated HOXL subclass genes as potential markers for esophageal squamous cell carcinoma detection.

BACKGROUND: Numerous studies have revealed aberrant DNA methylation in esophageal squamous cell carcinoma (ESCC). However, they often focused on the partial genome, which resulted in an inadequate understanding of the shaped methylation features and the lack of available methylation markers for this disease. METHODS: The current study investigated the methylation profiles between ESCC and paired normal samples using whole-genome bisulfite sequencing (WGBS) data and obtained a group of differentially methylated CpGs (DMC), differentially methylated regions (DMR), and differentially methylated genes (DMG). The DMGs were then verified in independent datasets and Sanger sequencing in our custom samples. Finally, we attempted to evaluate the performance of these genes as methylation markers for the classification of ESCC. RESULTS: We obtained 438,558 DMCs, 15,462 DMRs, and 1568 DMGs. The four significantly enriched gene families of DMGs were CD molecules, NKL subclass, HOXL subclass, and Zinc finger C2H2-type. The HOXL subclass homeobox genes were observed extensively hypermethylated in ESCC. The HOXL-score estimated by HOXC10 and HOXD1 methylation, whose methylation status were then confirmed by sanger sequencing in our custom ESCC samples, showed good ability in discriminating ESCC from normal samples. CONCLUSIONS: We observed widespread hypomethylation events in ESCC, and the hypermethylated HOXL subclass homeobox genes presented promising applications for the early detection of esophageal squamous cell carcinoma.

A novel stemness-hypoxia-related signature for prognostic stratification and immunotherapy response in hepatocellular carcinoma.

BACKGROUND: The specific differentiation potential, unlimited proliferation, and self-renewal capacity of cancer stem cells (CSCs) are closely related to the occurrence, recurrence, and drug resistance of hepatocellular carcinoma (HCC), as well as hypoxia. Therefore, an in-depth analysis of the relationship between HCC stemness, oxygenation status, and the effectiveness of immunotherapy is necessary to improve the poor prognosis of HCC patients. METHODS: The weighted gene co-expression network analysis (WGCNA) was utilized to find hypoxia-related genes, and the stemness index (mRNAsi) was evaluated using the one-class logistic regression (OCLR) technique. Based on stemness-hypoxia-related genes (SHRGs), population subgroup categorization using NMF cluster analysis was carried out. The relationship between SHRGs and survival outcomes was determined using univariate Cox regression. The LASSO-Cox regression strategy was performed to investigate the quality and establish the classifier associated with prognosis. The main effect of risk scores on the tumor microenvironment (TME) and its response to immune checkpoint drugs was also examined. Finally, qRT-PCR was performed to explore the expression and prognostic value of the signature in clinical samples. RESULTS: After identifying tumor stemness- and hypoxia-related genes through a series of bioinformatics analyses, we constructed a prognostic stratification model based on these SHRGs, which can be effectively applied to the prognostic classification of HCC patients and the prediction of immune checkpoint inhibitors (ICIs) efficacy. Independent validation of the model in the ICGC cohort yielded good results. In addition, we also constructed hypoxic cell models in Herp3B and Huh7 cells to verify the expression of genes in the prognostic model and found that C7, CLEC1B, and CXCL6 were not only related to the tumor stemness but also related to hypoxia. Finally, we found that the constructed signature had a good prognostic value in the clinical sample. CONCLUSIONS: We constructed and validated a stemness-hypoxia-related prognostic signature that can be used to predict the efficacy of ICIs therapy. We also verified that C7, CLEC1B, and CXCL6 are indeed associated with stemness and hypoxia through a hypoxic cell model, which may provide new ideas for individualized immunotherapy.

Novel high strength PVA/soy protein isolate composite hydrogels and their properties.

High strength polyvinyl alcohol (PVA)/soy protein isolate (SPI) composite hydrogels (EPSG) were constructed by the introduction of PVA into SPI through the crosslinking with epichlorohydrin (ECH) and a freezing-thawing process. The EPSG hydrogels were characterized by scanning electron microscopy, FTIR, X-ray diffraction and compressive test. The results revealed that chemical crosslinking interactions occurred for SPI and PVA during the fabrication process. The composite hydrogels exhibited a homogenous porous structure, indicating certain miscibility between PVA and SPI. The introduction of PVA increased the compressive strength of SPI hydrogels greatly, which could reach as high as 5.38 MPa with the water content ratio of 89.5%. Moreover, the water uptake ratio of completely dried SPI hydrogel (namely xerogel) decreased gradually from 327.4% to 148.1% with the incorporation of PVA, showing a better potential as implants. The cytocompatibility and hemocompatibility of the EPSG hydrogels were evaluated by a series of in vitro experiments. The results showed that the EPSG hydrogels had no cytotoxicity (cell viability values were above 86.7%), good biocompatibility and hemocompatibility, showing potential applications as a direct blood contact material in the field of tissue engineering.

Self-Healing Hyaluronic Acid Nanocomposite Hydrogels with Platelet-Rich Plasma Impregnated for Skin Regeneration.

The development of natural hydrogels with sufficient strength and self-healing capacity to accelerate skin wound healing is still challenging. Herein, a hyaluronic acid nanocomposite hydrogel was developed based on aldehyde-modified sodium hyaluronate (AHA), hydrazide-modified sodium hyaluronate (ADA), and aldehyde-modified cellulose nanocrystals (oxi-CNC). This hydrogel was formed in situ using dynamic acylhydrazone bonds via a double-barreled syringe. This hydrogel exhibited improved strength and excellent self-healing ability. Furthermore, platelet-rich plasma (PRP) can be loaded in the hyaluronic acid nanocomposite hydrogels (ADAC) via imine bonds formed between amino groups on PRP (e.g., fibrinogen) and aldehyde groups on AHA or oxi-CNC to promote skin wound healing synergistically. As expected, ADAC hydrogel could protect and release PRP sustainably. In animal experiments, ADAC@PRP hydrogel significantly promoted full-thickness skin wound healing through enhancing the formation of granulation tissue, facilitating collagen deposition, and accelerating re-epithelialization and neovascularization. This self-healing nanocomposite hydrogel with PRP loading appears to be a promising candidate for wound therapy.

The methylation of SDC2 and TFPI2 defined three methylator phenotypes of colorectal cancer.

BACKGROUND: Methylated SDC2 and TFPI2 are widely used for colorectal cancer (CRC) detection. However, they often miss some CRCs, which directly diminishes the sensitivity. Further investigations of the underlying mechanisms leading to the missed samples will facilitate developing more eligible methylation markers. METHODS: CRC samples from TCGA and GEO datasets were divided into three groups, High-methylation/ High-methylation (HH), High-methylation/Low-methylation (HL), and Low-methylation/Low-methylation (LL) according to the methylation status of SDC2 and TFPI2 promoters. Variations in age, tumor location and microsatellite instable were then assessed between the three groups and verified in our custom cohort. RESULTS: Samples of HL group preferred to derive from left-sided CRCs (P < 0.05). HH samples showed the highest microsatellite instability and mutation load (mean nonsynonymous mutations for HH/HL/LL: 10.55/3.91/7.02, P = 0.0055). Almost all mutations of BRAF, one of the five typical CpG island methylator phenotype (CIMP) related genes, were observed in HH group (HH/HL/LL: 51/0/1, P = 0.018). Besides, older patients were frequently found in HH group. Expression analysis identified 37, 84, and 22 group-specific differentially expressed genes (DEGs) for HH, HL, and LL, respectively. Functional enrichment analysis revealed that HH-specific DEGs were mainly related to transcription regulation, while LL-specific DEGs were enriched in the biological processes of extracellular matrix interaction and cell migration. CONCLUSIONS: The current study revealed that the performance of methylation-based markers might be affected by tumor location, patient age, mutation load and MSI, and these respective sides should be considered when developing new methylation markers for CRC detection.

Bio-polyols based waterborne polyurethane coatings reinforced with chitosan-modified ZnO nanoparticles.

The development of environmentally friendly waterborne polyurethane (WPU) coatings from bio-based polyols has received much attention due to increasing environmental concern and the depletion of petroleum resources. In this study, the WPU coatings derived from castor oil and soy polyol were modified by chain extender [bis(2-hydroxyethyl)amino]-methyl-phosphonic acid dimethyl ester. The effect of chitosan-modified ZnO (CS-ZnO) nanoparticles content on the properties of WPU/CS-ZnO coatings and their films were systematically investigated. The results indicated that WPU/CS-ZnO coatings displayed excellent storage stability and the particle sizes firstly decreased and then increased with CS-ZnO loading. CS-ZnO could improve tensile strength and Young's modulus but reduce the optical transparency of WPU/CS-ZnO films. CS-ZnO has a prominent reinforcement effect on the WPU/CS-ZnO matrix. With the addition of 2 wt% CS-ZnO, the tensile strength and Young's modulus of the WPU/CS-ZnO2 film reached 13.4 and 112.1 MPa, 1.68 and 2.6 times over neat WPU film, respectively. TGA results showed that the thermal stability of WPU/CS-ZnO films improved with increased CS-ZnO content. Furthermore, the WPU/CS-ZnO films' wettability decreased with the introduction of CS-ZnO. This work provides a simple and efficient strategy for preparing environmentally friendly bio-based WPU coatings, which are promising for application in the surface coating industry.

Biomimetic mineralization of novel hydroxyethyl cellulose/soy protein isolate scaffolds promote bone regeneration in vitro and in vivo.

Although various strategies have been utilized to accelerate bone regeneration in bone tissue engineering (BTE), the treatment and repair of large bone defects remains a clinical challenge worldwide. Inspired by the natural extracellular matrix of bone tissue, organic-inorganic composite scaffolds with three-dimensional (3D) porous structures, sufficient mechanical properties, excellent cytocompatibility, osteoconductivity, and osteogenic potential have received considerable attention within the field of bone engineering. In this work, a novel epichlorohydrin (ECH)-crosslinked hydroxyethyl cellulose (HEC)/soy protein isolate (SPI) porous bi-component scaffold (EHSS) with hydroxyapatite (HAp) functionalization (EHSS/HAp) was constructed for bone defect repair via the combination of lyophilization and in situ biomimetic mineralization. Systematic characterization experiments were performed to assess the morphology, HAp-forming properties, mechanical properties and degradation rate of the scaffold. The results indicated that the prepared scaffolds exhibited an interconnected porous structure, a biomimetic HAp coating on their surfaces, improved mechanical properties in compression and a controllable degradation rate. In particular, semiquantitative analysis showed that the calcium/phosphorus (Ca/P) ratio of EHSS/HAp with 70% SPI content (1.65) was similar to that of natural bone tissue (1.67) according to energy dispersive X-ray spectroscopy analysis. In vitro cell culture experiments indicated that the EHSS/HAp with 70% SPI content showed improved cytocompatibility and was suitable for MC3T3-E1 cell attachment, proliferation and growth. Consistently, in vitro osteogenic differentiation studies showed that EHSS/HAp with 70% SPI content can significantly accelerate the expression of osteogenesis-related genes (Col-1, Runx2, OPN, and OCN) during osteogenic differentiation of MC3T3-E1 cells. Furthermore, when applied to the repair of critical-sized cranial defects in a rat model, EHSS/HAp with 70% SPI was capable of significantly promoting tissue regeneration and integration with native bone tissue. Microscopic computed tomography (micro-CT) results demonstrated that the bone defect site was nearly occupied with newly formed bone at 12 weeks after implantation of EHSS/HAp with 70% SPI content into the defect. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining of histological sections further confirmed that EHSS/HAp with 70% SPI markedly promoted new bone formation and maturation. Collectively, our results demonstrate the potential of EHSS/HAp scaffolds with 70% SPI for successful bone defect repair and regeneration.

Shape memory histocompatible and biodegradable sponges for subcutaneous defect filling and repair: greatly reducing surgical incision.

Reducing surgical incision for large area subcutaneous defect filling and repair is a great challenge in the biomedical field, especially for plastic surgery. In this study, a novel hydroxyethyl cellulose/soy protein isolate (HEC/SPI) composite sponge (EHSS) with a fluid responsive shape memory property was constructed, whose thickness could be controlled by hot-pressing conditions to reduce the required surgical incision greatly. Effects of the main factors such as pressure, temperature and hot-pressing cycles on the recovery degree of EHSS were investigated systematically. The structure and physical properties of the sponges were characterized by FTIR spectroscopy, XRD, SEM etc. The results showed that EHSS could be pressed into thin disks with much smaller thickness, and the thickness retention ratio and recovery ratio were affected by hot-pressing conditions such as pressure and temperature. Especially, EHSS could be hot-pressed into a dense thin disk (EHSS-PT-130) at 130 °C with the pressure of 30 MPa, which could quickly recover its original shape by soaking in hydrophilic fluids. EHSS-PT-130 also exhibited good hydrophilicity, cytocompatibility, histocompatibility and in vivo biodegradability. Compared with the original EHSS, in vivo shape memory EHSS-PT-130 required much smaller surgical incision to reach the same repair effect and no need of extra sterilization, showing potential application for subcutaneous defect filling and repair.

Timely diagnosis and treatment of neonatal alloimmune thrombocytopenia caused by anti HPA-3a antibody: A case report.

RATIONALE: Neonatal alloimmune thrombocytopenia (NAIT) caused by anti HPA-3a antibody is rare, and the clinical features of the syndrome are not specific. PATIENT CONCERNS: A male infant was noted to be irritable and physical examination revealed the presence of petechiae and bruising on the right arm and thigh after born. DIAGNOSES: Platelet antibodies were investigated using the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay, platelet genotyping (HPA 1-17) was performed by polymerase chain reaction technique with sequence-specific primers (PCR-SSP). The HPA genotype of the newborn was HPA-3a/b, while that of his mother and his father were HPA-3b/b and HPA-3a/a, respectively. The sera of newborn contained antibody against the platelet of newborn's father. The HPA antibody of the newborn was identified as anti HPA-3a. The newborn was confirmed as a patient of NAIT caused by anti HPA-3a antibody. INTERVENTIONS: A single dose of intravenous immunoglobulin (IVIG) 1 g/kg was administered from day 3 to day 7. OUTCOMES: At follow-up 3 months after discharge from the hospital, the baby was developing normally and had a normal platelet count (361 × 109/L). LESSONS: NAIT caused by anti HPA-3a antibody is rare, and we believe this study can provide insights for diagnosing prospective cases. Prognosis of NAIT caused by HPA3a seems to be favorable if diagnosed and treated in a timely manner.

MicroRNA-30a Mediates Cell Migration and Invasion by Targeting Metadherin in Colorectal Cancer.

MicroRNAs play critical roles in the occurrence and progression in various cancers including colorectal cancer. Here, we found that microRNA-30a expression was significantly downregulated in colorectal cancer tissues compared to adjacent noncancerous tissues, and the suppression levels of microRNA-30a were significantly associated with tumor differentiation and lymph node metastasis. We also discovered that the expression level of microRNA-30a was inversely proportional to the invasive potential of several colorectal cancer cell lines. Moreover, overexpression of microRNA-30a in colorectal cancer cells inhibited activity of cell migration and invasion. Luciferase reporter assay confirmed metadherin could be a direct target of microRNA-30a, as the overexpression of microRNA-30a decreased metadherin expression at both the protein and messenger RNA levels. Furthermore, the knockdown of metadherin expression in SW620 significantly decreased cell metastasis and invasion. The upregulation of metadherin at the protein level negatively correlated with the expression of microRNA-30a in colorectal cancer tissues, and this upregulation could partially attenuate the effect induced by microRNA-30a. These findings indicate that microRNA-30a may act as a tumor suppressor in colorectal cancer and that microRNA-30a represses cell migration and invasion by decreasing metadherin, highlighting the therapeutic potential of microRNA-30a and metadherin in colorectal cancer treatment.

Enhanced Peripheral Nerve Regeneration by a High Surface Area to Volume Ratio of Nerve Conduits Fabricated from Hydroxyethyl Cellulose/Soy Protein Composite Sponges.

Multichannel nerve guide conduits (MCNGCs) have been widely studied and exhibited outstanding nerve repair function. However, the effect of the geometric structure of MCNGCs on the nerve repair function was still not clear. Herein, we postulated that MCNGCs with different inner surface area-to-volume ratios (ISA/V) of the channels inside the nerve guide conduits (NGCs) would show different nerve repair functions. Therefore, in current work, we constructed a series of hydroxyethyl cellulose/soy protein sponge-based nerve conduit (HSSN) with low, medium, and high ISA/V from hydroxyethyl cellulose (HEC)/soy protein isolate (SPI) composite sponges, which were abbreviated as HSSN-L, HSSN-M and HSSN-H, respectively. These NGCs were applied to bridge and repair a 10 mm long sciatic nerve defect in a rat model. Finally, the influence of ISA/V on nerve repair function was evaluated by electrophysiological assessment, histological investigation, and in vivo biodegradability testing. The results of electrophysiological assessment and histological investigation showed that the regenerative nerve tissues bridged with HSSN-H and HSSN-M had higher compound muscle action potential amplitude ratio, higher percentage of positive NF200 and S100 staining, larger axon diameter, lower G-ratio, and greater myelination thickness. Furthermore, the regenerative nerve tissues bridged with HSSN-H also showed higher density of regenerated myelinated nerve fibers and more number of myelin sheath layers. On the whole, the repair efficiency of the peripheral nerve in HSSN-H and HSSN-M groups might be better than that in HSSN-L. These results indicated that higher ISA/V based on HEC/SPI composite sponge may result in greater nerve repair functions. The conclusion provided a probable guiding principle for the structural designs of NGCs in the future.

Strong and Rapidly Self-Healing Hydrogels: Potential Hemostatic Materials.

Benzaldehyde-terminated telechelic four-armed polyethylene glycol (PEG-BA) is synthesized and cross-linked with carboxymethyl chitosan (CMC) to form dynamic hydrogels with strong mechanical performance. The gelation temperature and time, mechanical performance, and self-healing behaviors are systematically investigated. The hydrogels have good storage modulus up to 3162.06 ± 21.06 Pa, comparable to conventional bulk hydrogels. The separated alternate hydrogel lines connect together to become an integrated hydrogel film after 5 min at room temperature without any external intervention. This is due to the dynamic equilibrium between the Schiff base linkages and the aldehyde groups of PEG-BA and amine groups on CMC backbone. The hydrogel shows excellent cytocompatibility and the cell viability is as high as 90.7 ± 6.8% after 2 d 3D encapsulation in the hydrogel. In vivo tests indicate that the hydrogels can effectively stop bleeding when the hydrogel is directly injected into a rabbit liver incision. The total blood loss is reduced from 0.65 ± 0.10 g to 0.29 ± 0.11 g, and the hemostasis time is decreased from 167 ± 21 s to 120 ± 10 s, when compared to a gauze treatment with physical compression. These self-healing hydrogels have potential to be used as a novel hemostatic material.

Cellulose/soy protein composite-based nerve guidance conduits with designed microstructure for peripheral nerve regeneration.

OBJECTIVE: The objective of this work was to develop nerve guidance conduits from natural polymers, cellulose and soy protein isolate (SPI), by evaluating the effects of cellulose/SPI film-based conduit (CSFC) and cellulose/SPI sponge-based conduit (CSSC) on regeneration of nerve defects in rats. APPROACH: CSFC and CSSC with the same chemical components were fabricated from cellulose and SPI. Effects of CSSC and CSFC on regeneration of the defective nerve were comparatively investigated in rats with a 10 mm long gap in sciatic nerve. The outcomes of peripheral nerve repair were evaluated by a combination of electrophysiological assessment, Fluoro-Gold retrograde tracing, double NF200/S100 immunofluorescence analysis, toluidine blue staining, and electron microscopy. The probable molecular mechanism was investigated using quantitative real-time PCR (qPCR) analysis. MAIN RESULTS: Compared with CSFC, CSSC had 2.69 times higher porosity and 5.07 times higher water absorption, thus ensuring much higher permeability. The nerve defects were successfully bridged and repaired by CSSC and CSFC. Three months after surgery, the CSSC group had a higher compound muscle action potential amplitude ratio, a higher percentage of positive NF200 and S100 staining, and a higher axon diameter and myelin sheath thickness than the CSFC group, showing the repair efficiency of CSSC was higher than that of CSFC. qPCR analysis indicated the mRNA levels of nerve growth factor, IL-10, IL-6, and growth-associated protein 43 (GAP-43) were higher in the CSSC group. This also indicated that there was better nerve repair with CSSC due to the higher porosity and permeability of CSSC providing a more favourable microenvironment for nerve regeneration than CSFC. SIGNIFICANCE: A promising nerve guidance conduit was developed from cellulose/SPI sponge that showed potential for application in the repair of nerve defect. This work also suggests that nerve guidance conduits with better repair efficiency could be developed through structure design and processing optimization.

Improved Mechanical Properties and Sustained Release Behavior of Cationic Cellulose Nanocrystals Reinforeced Cationic Cellulose Injectable Hydrogels.

Polysaccharide-based injectable hydrogels have several advantages in the context of biomedical use. However, the main obstruction associated with the utilization of these hydrogels in clinical application is their poor mechanical properties. Herein, we describe in situ gelling of nanocomposite hydrogels based on quaternized cellulose (QC) and rigid rod-like cationic cellulose nanocrystals (CCNCs), which can overcome this challenge. In all cases, gelation immediately occurred with an increase of temperature, and the CCNCs were evenly distributed throughout the hydrogels. The nanocomposite hydrogels exhibited increasing orders-of-magnitude in the mechanical strength, high extension in degradation and the sustained release time, because of the strong interaction between CCNCs and QC chains mediated by the cross-linking agent (ß-glycerophosphate, ß-GP). The results of the in vitro toxicity and in vivo biocompatibility tests revealed that the hydrogels did not show obvious cytotoxicity and inflammatory reaction to cells and tissue. Moreover, DOX-encapsulated hydrogels were injected beside the tumors of mice bearing liver cancer xenografts to assess the potential utility as localized and sustained drug delivery depot systems for anticancer therapy. The results suggested that the QC/CCNC/ß-GP nanocomposite hydrogels had great potential for application in subcutaneous and sustained delivery of anticancer drug to increase therapeutic efficacy and improve patient compliance.