Silk Fibroin-Based Tough Hydrogels with Strong Underwater Adhesion for Fast Hemostasis and Wound Sealing.

Rapid and strong adhesion of hydrogel adhesives is required for instant wound closure and hemostasis. However, in situ hydrogel formation and sufficient adhesion at target tissue sites in biological environments are severely compromised by the presence of blood and body fluids. In this work, an underwater adhesive hydrogel (named SHCa) is fabricated with rapid in situ gelation, enhanced mechanical toughness, and robust underwater adhesion. The SHCa can undergo rapid UV irradiation-induced gelation under water within 5 s and adhere firmly to underwater surfaces for 6 months. The synergistic effects of crystalline ß-sheet structures and dynamic energy-dissipating mechanisms enhance the mechanical toughness and cohesion, supporting the balance between adhesion and cohesion in wet environments. Importantly, the SHCa can achieve rapid in situ gelation and robust underwater adhesion at various tissue surfaces in highly dynamic fluid environments, substantially outperforming the commercially available tissue adhesives. The lap shear adhesion strength and wound closure strength of SHCa on blood-covered substrates are 7.24 and 12.68 times higher than those of cyanoacrylate glue, respectively. Its fast hemostasis and wound sealing performance are further demonstrated in in vivo animal models. The proposed hydrogel with strong underwater adhesion provides an effective tool for fast wound closure and hemostasis.

Time-dependent immune injury induced by short-term exposure to nanoplastics in the Sepia esculenta larvae.

Marine organisms are threatened by various environmental contaminants, and nanoplastics (NPs) is one of the most concerned. Studied have shown that NPs has a certain impact on marine organisms, but the specific molecular mechanism is still unclear. At present, researches on the effect of NPs on marine life mostly focus on crustaceans, gastropods, and bivalves. In this study, cephalopod Sepia esculenta larvae were first used to investigate the potential immune response molecular mechanisms caused by PS-NPs (50 nm, 50 mg/L) short-term exposure (4 and 24 h). Through S. esculenta larvae transcriptome profile of gene expression analysis, 548 and 1990 genes showed differential expression at 4 and 24 h after NPs exposure, respectively. GO and KEGG enrichment analysis were performed to find immune related DEGs. Then, the interaction relationship between the immune related DEGs after NPs exposure was known through the constructed protein-protein interaction network. 20 hub genes were found on the base of KEGG pathway numbers involved and protein-protein interaction numbers. This research supply valuable genes for the study of cephalopod immune response caused by NPs, which can help us further uncover the molecular mechanisms of organism against NPs.

Highly Electrically Conductive Flexible Ionogels by Drop-Casting Ionic Liquid/PEDOT:PSS Composite Liquids onto Hydrogel Networks.

Ionogels have been extensively studied as ideal flexible and stretchable materials by virtue of the unique properties of ionic liquids, such as non-volatility, non-flammability, and negligible vapor pressure. However, the generally low ionic conductivity of the current ionogels limits their applications in the market of highly conductive, flexible, and stretchable electrical devices. Here, the fabrication of highly electrically conductive ionogels is reported by combining composite liquids consisting of 1-ethyl-3-methylimidazolium dicyanamide ([EMIM][DCA]) and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) with flexible negative-charged poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPS) hydrogel. The generated composite film exhibits high electrical conductivity up to about 38 S cm-1 with the maximum tensile strain of 45% and fracture stress of 27 kPa. In addition, it is demonstrated that the composite film can maintain conductivity in a high level under different mechanical deformations, and can also be used as flexible sensors in a wide temperature range from -58 to 120 ℃. It is believed that the designed composite film would expand the applications of flexible conductive materials where both high conductivity and robust mechanical flexibility are required.

A compact immunoassay platform based on a multicapillary glass plate.

A highly sensitive, rapid immunoassay performed in the multi-channels of a micro-well array consisting of a multicapillary glass plate (MCP) and a polydimethylsiloxane (PDMS) slide is described. The micro-dimensions and large surface area of the MCP permitted the diffusion distance to be decreased and the reaction efficiency to be increased. To confirm the concept of the method, human immunoglobulin A (h-IgA) was measured using both the proposed immunoassay system and the traditional 96-well plate method. The proposed method resulted in a 1/5-fold decrease of immunoassay time, and a 1/56-fold cut in reagent consumption with a 0.05 ng/mL of limit of detection (LOD) for IgA. The method was also applied to saliva samples obtained from healthy volunteers. The results correlated well to those obtained by the 96-well plate method. The method has the potential for use in disease diagnostic or on-site immunoassays.

Biomimetic injectable and bilayered hydrogel scaffold based on collagen and chondroitin sulfate for the repair of osteochondral defects.

The simultaneous regeneration of articular cartilage and subchondral bone is a major challenge. Bioinspired scaffolds with distinct regions resembling stratified anatomical architecture provide a potential strategy for osteochondral defect repair. Here, we report the development of an injectable and bilayered hydrogel scaffold with a strong interface binding force. In this bilayer hydrogel, composed of carbonyl hydrazide grafted collagen (COL-CDH) and oxidized chondroitin sulfate (OCS), which are derivatives of osteochondral tissue components, in combination with poly (ethylene glycol) diacrylate (PEGDA), functions as a cartilage layer; while zinc-doped hydroxyapatite acts as a subchondral bone layer that is based on the cartilage layer. The strong interface between the two layers involves dynamic amide bonds formed between COL-CDH and OCS, and permanent CC bonds formed by PEGDA radical reactions. This bilayer hydrogel can be used to inoculate adipose mesenchymal stem cells which can then differentiate into chondrocytes and osteoblasts, secreting glycosaminoglycan, and promoting calcium deposition. This accelerates the regeneration of cartilage and subchondral bone. Micro-CT and tissue staining revealed an increase in the amount of bone present in new subchondral bone, and new tissues with a structure similar to normal cartilage. This study therefore demonstrates that injectable bilayer hydrogels are a promising scaffold for repairing osteochondral defects.

Electrospun Biomimetic Periosteum Capable of Controlled Release of Multiple Agents for Programmed Promoting Bone Regeneration.

The effective repair of large bone defects remains a major challenge due to its limited self-healing capacity. Inspired by the structure and function of the natural periosteum, an electrospun biomimetic periosteum is constructed to programmatically promote bone regeneration using natural bone healing mechanisms. The biomimetic periosteum is composed of a bilayer with an asymmetric structure in which an aligned electrospun poly(ε-caprolactone)/gelatin/deferoxamine (PCL/GEL/DFO) layer mimics the outer fibrous layer of the periosteum, while a random coaxial electrospun PCL/GEL/aspirin (ASP) shell and PCL/silicon nanoparticles (SiNPs) core layer mimics the inner cambial layer. The bilayer controls the release of ASP, DFO, and SiNPs to precisely regulate the inflammatory, angiogenic, and osteogenic phases of bone repair. The random coaxial inner layer can effectively antioxidize, promoting cell recruitment, proliferation, differentiation, and mineralization, while the aligned outer layer can promote angiogenesis and prevent fibroblast infiltration. In particular, different stages of bone repair are modulated in a rat skull defect model to achieve faster and better bone regeneration. The proposed biomimetic periosteum is expected to be a promising candidate for bone defect healing.

Inkjet nanoinjection for high-thoughput chemiluminescence immunoassay on multicapillary glass plate.

We report a novel chemiluminescence diagnosis system for high-throughput human IgA detection by inkjet nanoinjection on a multicapillary glass plate. As proof-of-concept, microhole-based polydimethylsiloxane (PDMS) sheets were aligned on a multicapillary glass plate to form a microwell array as microreactors for enzyme-linked immunosorbent assay (ELISA). The multicapillary glass plate was utilized as a switch that controlled the holding/passing of the solution. Further, anti-IgA-labeled polystyrene (PS) microbeads was assembled into the microwell array, and an inkjet nanoinjection was specially used to distribute the sample and reagent solution for chemiluminescence ELISA, enabling high-throughput detection of human IgA. As a result, the performance of human IgA tests revealed a wider range for the calibration curve and a lower limit of detection (LOD) of 0.1 ng mL(-1) than the ELISA by a standard 96-well plate. The analysis time and reagent consumption were significantly decreased. The IgA concentrations in saliva samples were determined after 10000-fold dilution by the developed ELISA system showing comparable results by conventional immune assay with 96-wells. Thus, we believe that the inkjet nanoinjection for high-throughput chemiluminescence immunoassay on a multicapillary glass plate will be promising in disease diagnosis.

Effects of Various Cell Surface Engineering Reactions on the Biological Behavior of Mammalian Cells.

Cell surface engineering technologies can regulate cell function and behavior by modifying the cell surface. Previous studies have mainly focused on investigating the effects of cell surface engineering reactions and materials on cell activity. However, they do not comprehensively analyze other cellular processes. This study exploits covalent bonding, hydrophobic interactions, and electrostatic interactions to modify the macromolecules succinimide ester-methoxy polyethylene glycol (NHS-mPEG), distearoyl phosphoethanolamine-methoxy polyethylene glycol (DSPE-mPEG), and poly-L-lysine (PLL), respectively, on the cell surface. This work systematically investigates the effects of the three surface engineering reactions on the behavior of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts, including viability, growth, proliferation, cell cycle, adhesion, and migration. The results reveals that the PLL modification method notably affects cell viability and G2/M arrest and has a short modification duration. However, the DSPE-mPEG and NHS-mPEG modification methods have little effect on cell viability and proliferation but have a prolonged modification duration. Moreover, the DSPE-mPEG modification method highly affects cell adherence. Further, the NHS-mPEG modification method can significantly improve the migration ability of HUVECs by reducing the area of focal adhesions. The findings of this study will contribute to the application of cell surface engineering technology in the biomedical field.

Acute effects of polystyrene nanoplastics on the immune response in Sepia esculenta larvae.

With extensive use of plastic products, microplastics (MPs, < 5 mm) and nanoplastics (NPs, < 1 µm) have become major pollutants in ecosystem, especially in marine environment. In recent years, researches on the impact of NPs on organisms have gradually increased. However, studies on the influence of NPs on cephalopods are still limited. Golden cuttlefish (Sepia esculenta), an important economic cephalopod, is a shallow marine benthic organism. In this study, the effect of acute exposure (4 h) to 50-nm polystyrene nanoplastics (PS-NPs, 100 µg/L) on the immune response of S. esculenta larvae was analyzed via transcriptome data. A total of 1260 DEGs were obtained in the gene expression analysis. The analyses of GO, KEGG signaling pathway enrichment, and protein-protein interaction (PPI) network were then performed to explore the potential molecular mechanisms of the immune response. Finally, 16 key immune-related DEGs were obtained according to the number of KEGG signaling pathways involved and the PPI number. This study not only confirmed that NPs had an impact on cephalopod immune response, but also provided novel insights for further unmasking the toxicological mechanisms of NPs.

Multi-crosslinked hydrogels with strong wet adhesion, self-healing, antibacterial property, reactive oxygen species scavenging activity, and on-demand removability for seawater-immersed wound healing.

In general, seawater-immersed wounds are associated with tissue necrosis, infection, prolonged healing period, and high mortality because of high salinity, hyperosmosis, and the presence of various pathogenic bacteria in seawater. However, current wound dressings can hardly achieve strong and stable wet adhesion and antibacterial properties, thus limiting their application to seawater-immersed wounds. Here a multifunctional hydrogel (OD/EPL@Fe) comprising catechol-modified oxidized hyaluronic acid (OD), ε-poly-L-lysine (EPL), and Fe3+ was prepared primarily through Schiff-base reaction, metal chelation, cation-π, and electrostatic interaction. The hydrogel with high wet adhesion (about 78 kPa) was achieved by combining the mussel-inspired strategy, dehydration effect, and cohesion enhancement, which is higher than that of commercial fibrin glues and cyanoacrylate glues. Meanwhile, the hydrogel can eliminate Marine bacteria (V. vulnificus and P. aeruginosa) and inhibit their biofilm formation. In addition, the hydrogel demonstrated injectability, self-healing, reactive oxygen species scavenging activity, photothermal effect, seawater isolation, on-demand removal, and hemostatic properties. In vivo results showed that the hydrogel had good adhesion to dynamic wounds in a rat neck full-thickness skin wound model. In particular, the hydrogel exhibited antibacterial, anti-inflammatory, and antioxidant properties in a rat seawater-immersed infected wound model and accelerated the reconstruction of skin structure and functions. The results demonstrated that the OD/EPL@Fe would be a potential wound dressing for seawater-immersed wound healing. STATEMENT OF SIGNIFICANCE: A multifunctional OD/EPL@Fe hydrogel has been prepared for the treatment of seawater-immersed wounds. The hydrogel with high wet adhesion was achieved by combining the mussel-inspired strategy, dehydration effect, and cohesion enhancement. The results revealed that the wet adhesion value of hydrogel was about eight times greater than commercial fibrin glues and 1.5 times greater than commercial cyanoacrylate glues. The hydrogel can be easily removed after being sprayed with deferoxamine mesylate. Notably, the inherent antimicrobial material of the hydrogel combined with the photothermal effect can eliminate marine bacteria and inhibit their biofilm formation. Moreover, the hydrogel can accelerate the healing of seawater-immersed infected wound on mice.

ProBDNF signaling is involved in periodontitis-induced depression-like behavior in mouse hippocampus.

OBJECTIVE: Increasing evidence supports the association between periodontitis and depression. However, the specific mechanisms remain to be further elucidated. The present study aimed to mechanistically investigate the regional roles of proBDNF (the precursor of brain-derived neurotrophic factor) in periodontitis induced depression-like behavior in mice. METHODS: Experimental periodontitis model was established by periodontal injection of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) in 8-week-old male Bdnf-HA/HA mice for 3 weeks. The depression-like behaviors, spontaneous exploratory activity and the level of anxiety were assessed by behavior tests. The activation of microglia and astrocytes, as well as the expression of Interleukin (IL)-1ß and Tumor necrosis factor (TNF)-α in the hippocampus, prefrontal cortex, and cortex were further assessed by immunofluorescence and western blots. The levels of IL-1ß in blood serum and expression of occludin as well as claudin5 in the hippocampus, prefrontal cortex, and cortex were further determined by enzyme-linked immunosorbent assay and western blot. Finally, the expression of proBDNF, its receptors, and mature BDNF (mBDNF), as well as neuronal activity were measured by western blots and immunofluorescence. RESULTS: Pg-LPS successfully induced periodontitis in mice and caused obvious depression-like behavior. Furthermore, we observed an increased activation of astrocytes and microglia, as well as a significant increase in expression of IL-1ß and TNF-α in the hippocampus of mice treated with Pg-LPS, with elevated level of IL-1ß in serum and decreased expression of occludin and claudin5 in the hippocampus. Importantly, we found that the levels of proBDNF and its receptors, SorCS2 and p75NTR, were increased significantly; however, the level of mBDNF was decreased, therefor leading to greater ratio of proBDNF/mBDNF. In addition, we also detected decreased neuronal activity in the hippocampus of mice treated with Pg-LPS. CONCLUSIONS: Our results indicate that Pg-LPS-induced periodontitis could cause depression-like behaviors in mice, and the proBDNF signaling is involved in the process.

Gremlin aggravates periodontitis via activation of the nuclear factor-kappa B signaling pathway.

BACKGROUND: Gremlin has been reported to regulate inflammation and osteogenesis. Periodontitis is a destructive disease degenerating periodontal tissues, therefore leads to alveolar bone resorption and tooth loss. Based on the importance of Gremlin's bio-activity, the aim of this study is to, in vivo and in vitro, unveil the function of Gremlin in regulating the development of periodontitis and its consequent effects on alveolar bone loss. METHODS: Clinical specimens were used to determine the expression of Gremlin in periodontal tissues by immunohistochemical staining and western blot. Then utilizing the rat periodontitis model to investigate the function of gremlin-regulated nuclear factor-kappa B (NF-κB) pathway during the development of periodontal inflammation and the alveolar bone loss. Last, the regulation of the osteogenesis of human periodontal ligament stem cells (hPDLSCs) by Gremlin under inflamed condition was analyzed by alkaline phosphatase (ALP) and alizarin red staining (ARS). RESULTS: We found clinically and experimentally that the expression of Gremlin is markedly increased in periodontitis tissues. Interestingly, we revealed that Gremlin regulated the progress of periodontitis via regulating the activities of NF-κB pathway and interleukin-1ß (IL-1ß). Notably, we observed that Gremlin influenced the osteogenesis of hPDLSCs. Thus, our present study identified Gremlin as a new key regulator for development of periodontitis. CONCLUSIONS: Our current study illustrated that Gremlin acts as a crucial mediator and possibly serves as a potential diagnostic marker for periodontitis. Discovery of new factors involved in the pathophysiology of periodontitis could contribute to the development of novel therapeutic treatment for the disease.

Smartphone-based reading system integrated with phycocyanin-enhanced latex nanospheres immunoassay for on-site determination of aflatoxin B1 in foodstuffs.

Traditional methods for aflatoxin B1 (AFB1) detection are complex, time-consuming, labor-intensive, and high cost. Moreover, they require sophisticated large-scale instrumentation, which limits their on-site rapid detection. Herein, phycocyanin fluorescent nanospheres based on fluorescence immunochromatographic assay were developed for quantitative detection of AFB1 at parts-per-billion (ppb) levels in foodstuffs. Phycocyanin and anti-AFB1 monoclonal antibodies were coupled on the surface of latex nanospheres to amplify the fluorescence signal and improve the sensitivity. The fluorescence intensity was measured by a self-developed smartphone-based reading system. Under the optimal conditions, this approach achieved quantitative point-of-care detection of AFB1 within 25 min. The calibration curve for AFB1 was linear in the range of 0.2-48 ppb, and the limit of detection was 0.16 ppb. The practical applicability of the proposed approach was demonstrated by the determination of AFB1 in naturally contaminated samples, and the results were consistent with HPLC detection.

Crosstalk between Wnt/ß-catenin signaling and NF-κB signaling contributes to apical periodontitis.

In physiology conditions, the crosstalk of signaling pathways has been considered to extend the functions of individual pathways and results in a more complex regulatory network. The Wnt3a/ß-catenin and NF-κB signaling pathways have been demonstrated involving in apical periodontitis (AP). As AP progresses, ultimately causes tooth loss. In the present study, we investigate the contribution of the crosstalk between the Wnt3a/ß-catenin and NF-κB signaling pathways to the development of AP. Clinically, utilizing 60 human AP and healthy tissues (30 samples for each group), we found that the expression levels of Wnt3a/ß-catenin and NF-κB were elevated in the Ap tissues compared to that in the healthy group. To further study the roles of Wnt3a/ß-catenin and NF-κB signaling pathways in the development of AP, and the contribution of the crosstalk between these two signaling pathways to AP, we established the AP animal model and observed that, first, both pathways are activated in the AP group compared to the control group. Interestingly, by immunoprecipitation and western blot experiments, we revealed that there is greater interaction between NF-κB (phorspho-p65) and ß-catenin in AP tissues compared to the control tissues. Importantly, when the NF-κB signaling pathway was blocked by its inhibitor, pyrrolidine dithiocarbamate (PDTC), the activity of the Wnt3a/ß-catenin signaling pathway was abolished, and consequently led to the attenuation of the inflammation response in LPS-induced human periodontal ligament cells (hPDLCs). Thus, our data indicate that the crosstalk between Wnt3a/ß-catenin and NF-κB signaling pathway contributes to the development of AP, and provide a therapeutic strategy for the treatment of AP as well.

Screening of differentially expressed miRNAs during osteogenic/odontogenic differentiation of human dental pulp stem cells exposed to mechanical stress.

MicroRNAs (miRNAs) have been demonstrated as crucial transcriptional regulators in proliferation, differentiation, and tumorigenesis. The comprehensive miRNA profiles of osteogenic/odontogenic differentiation of human dental pulp stem cells (hDPSCs) under the condition of mechanical stress remains largely unknown. In this study, we aimed to discover the miRNA expression profiles of hDPSCs exposed to mechanical stress under the osteogenic/odontogenic process. We found that mechanical stress (0.09 MPa and 0.18 MPa, respectively, 30 min/day) significantly promoted the proliferation of hDPSCs since the fifth day. The expressions of DSPP, DMP1, and RUNX2 were significantly increased on day 7 in the presence of 0.09 MPa and 0.18 MPa mechanical stress. On day 14, the expression levels of DSPP, DMP1, and RUNX2 were decreased in the presence of mechanical stress. Among 2578 expressed miRNAs, 5 miRNAs were upregulated and 3 miRNAs were downregulated. Six hub target genes were merged in protein-protein interactions (PPI) network analysis, in which existed only one sub-network. Bioinformatics analysis identified an array of affected signaling pathways involved in the development of epithelial and endothelial cells, cell-cell junction assembly, Rap1 signaling pathway, regulation of actin cytoskeleton, and MAPK signaling pathway. Our results revealed the miRNA expression profiles of osteogenic/odontogenic differentiation of hDPSCs under mechanical stress and identified eight miRNAs that were differentially expressed in response to the mechanical stress. Bioinformatics analysis also showed that various signaling pathways were affected by mechanical stress.

Transglutaminase-Catalyzed Encapsulation of Individual Mammalian Cells with Biocompatible and Cytoprotective Gelatin Nanoshells.

Mammalian cells are extremely vulnerable to external assaults compared with plant and microbial cells because of the weakness of cell membranes compared with cell walls. Construction of ultrathin and robust artificial shells on mammalian cells with biocompatible materials is a promising strategy for protecting single cells against harsh environmental conditions. Herein, layer-by-layer assembly combined with a transglutaminase-catalyzed cross-linking reaction was employed to prepare cross-linked and biocompatible gelatin nanoshells on individual human cervical carcinoma cell line (HeLa) cells and mouse insulinoma cell line 6 (MIN6) cells. The encapsulated HeLa and MIN6 cells showed high viability and a prolonged encapsulation period. Moreover, the nanoshells can protect encapsulated cells from cytotoxic enzymes (such as trypsin) and polycation (polyethylenimine) attacks and help cells resist high physical stress. We also investigated how nanoshells would affect the cell viability, proliferation, and cell cycle distribution of encapsulated and released cells. The approach presented here may provide a new and versatile method for nanoencapsulation of individual mammalian cells, which would help cells endure various environmental stresses and thereby expand the application field of isolated mammalian cells.

Encapsulation of individual living cells with enzyme responsive polymer nanoshell.

Cell delivery in cell therapy is typically challenged by the low cell survival rate and immunological rejection during cells injection and circulation. Encapsulation of cells with semipermeable hydrogels or membranes can improve cell viability by resisting high shear force and inhibit immune response with the physical isolation effect. Herein, the individual HeLa cells and human mesenchymal stem cells (hMSCs) were encapsulated with enzyme responsive polymer nanoshell. The encapsulation shell was prepared via the Layer-by-Layer (LbL) assembly of functionalized gelatin and click chemistry of peptide linker and gelatin. The encapsulated cells showed high cell viability and could resist the physical stress. Moreover, the encapsulation shell had a prolonged encapsulation sustaining period and could effectively prevent the invasion of external entities. In addition, on-site cell release was realized via enzymolysis of the encapsulation shell by human matrix metalloproteinase-7 (MMP-7), an overexpressed enzyme on tumor area. The finding of this study proved a potential approach in cell therapy, especially for cell-based cancer therapy.

Preparation of biocompatible wound dressings with long-term antimicrobial activity through covalent bonding of antibiotic agents to natural polymers.

Wound dressings with long-term antimicrobial activity are highly desired for treatment of chronic wound infections. Herein, the sustained antimicrobial wound dressings were developed by using antibiotic agents, ciprofloxacin HCL (CIP) and gentamicin sulfate (GS), covalent bonding to natural polymer matrix composites, carboxymethyl chitosan (CMC) and collagen (COL). By amide bond formation between antibiotic agents and polymer chains, two antimicrobial wound dressings CMC-COL-CIP and CMC-COL-GS were prepared. The presented wound dressings exhibited high water absorption capacity, excellent water vapor transmission rate (WVTR), appropriate mechanical properties, and impressive stability. Cytocompatibility of the dressings was demonstrated by in vitro human skin fibroblast (HSF) cells culture study. The results of in vitro and in vivo studies indicated that the two antimicrobial wound dressings have effective antimicrobial activity and prolonged antimicrobial period. Furthermore, the antimicrobial dressings could promote the wound healing, reepithelialization, collagen deposition, and angiogenesis. It also displays superiority wound healing effects compared to commercially available silver-based dressings (Aguacel Ag). This work indicates that the prepared antimicrobial wound dressings have great potential application in chronic wound healing, such as severe wound cure and diabetic foot ulcers.

Transglutaminase-catalyzed preparation of crosslinked carboxymethyl chitosan/carboxymethyl cellulose/collagen composite membrane for postsurgical peritoneal adhesion prevention.

Peritoneal adhesion is a general complication following pelvic and abdominal surgery, which may lead to chronic abdominal pain, bowel obstruction, organ injury, and female infertility. Biodegradable polymer membranes have been suggested as physical barriers to prevent peritoneum adhesion. In this work, a transglutaminase (TGase)-catalyzed crosslinked carboxymethyl chitosan/carboxymethyl cellulose/collagen (CMCS/CMCL/COL) composite anti-adhesion membrane with various proportions of CMCS, CMCL, and COL (40/40/20, 35/35/30, 25/25/50) was developed. After crosslinking by TGase, the composite anti-adhesion membranes shown enhanced mechanical properties and improved biodegradability. Meanwhile, the high cytocompatibility of anti-adhesion membranes was proved by in vitro cell culture study. Moreover, the anti-adhesion membrane with the proportion of 25/25/50 was implanted between the artificially defected cecum and peritoneal wall in rats and following by general observation, histological examination, and inflammatory factors assay. The results indicated that the anti-adhesion membrane can significantly prevent peritoneal adhesion with negligible immunogenicity. Therefore, the composite membrane crosslinked by TGase had satisfactory anti-adhesive effects with high biocompatibility and low antigenicity, which could be used as a preventive barrier for peritoneal adhesion.

Nanoencapsulation of individual mammalian cells with cytoprotective polymer shell.

Nanoencapsulation of individual mammalian cells has great potential in biomedical, biotechnological and bioelectronic applications. However, existing techniques for cell nanoencapsulation generally yield short sustaining period and loose structure of encapsulation shell, which fails to meet the long-term cytoprotection and immunosuppression requirements. Here, we report a mild method to realize the nanoencapsulation of individual mammalian cells by layer-by-layer (LbL) assembly of gelatin inner layer and cross-linking of poly(ethylene glycol) (PEG) outer layer through thiol-click chemistry. With the present method, the encapsulated individual HeLa cells showed a high viability, long persistence period and effective resistance against macro external entities and high physical stress. Moreover, on-demand cell release could also be achieved by selective cleavage of succinimide thioether linkage in the outer PEG layer. The approach presented here may provide a new and versatile method for the cleavable nanoencapsulation of individual mammalian cells.