Facilitating safe and sustained submucosal lift through an endoscopically injectable shear-thinning carboxymethyl starch sodium hydrogel.

Traditional submucosal filling materials frequently show insufficient lifting height and duration during clinical procedures. Here, the anionic polysaccharide polymer sodium carboxymethyl starch and cationic Laponite to prepare a hydrogel with excellent shear-thinning ability through physical cross-linking, so that it can achieve continuous improvement of the mucosal cushion through endoscopic injection. The results showed that the hydrogel (56.54 kPa) had a lower injection pressure compared to MucoUp (68.56 kPa). The height of submucosal lifting height produced by hydrogel was higher than MucoUp, and the height maintenance ability after 2 h was 3.20 times that of MucoUp. At the same time, the hydrogel also showed satisfactory degradability and biosafety, completely degrading within 200 h. The hemolysis rate is as low as 0.76 %, and the cell survival rate > 80 %. Subcutaneous implantation experiments confirmed that the hydrogel showed no obvious systemic toxicity. Animal experiments clearly demonstrated the in vivo feasibility of using hydrogels for submucosal uplift. Furthermore, successful endoscopic submucosal dissection was executed on a live pig stomach, affirming the capacity of hydrogel to safely and effectively facilitate submucosal dissection and mitigate adverse events, such as bleeding. These results indicate that shear-thinning hydrogels have a wide range applications as submucosal injection materials.

Effectiveness of intraoperative peritoneal lavage with saline in patient with intra-abdominal infections: a systematic review and meta-analysis.

BACKGROUND: Intraoperative peritoneal lavage (IOPL) with saline has been widely used in surgical practice. However, the effectiveness of IOPL with saline in patients with intra-abdominal infections (IAIs) remains controversial. This study aims to systematically review randomized controlled trials (RCTs) evaluating the effectiveness of IOPL in patients with IAIs. METHODS: The databases of PubMed, Embase, Web of Science, Cochrane library, CNKI, WanFang, and CBM databases were searched from inception to December 31, 2022. Random-effects models were used to calculate the risk ratio (RR), mean difference, and standardized mean difference. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to rate the quality of the evidence. RESULTS: Ten RCTs with 1318 participants were included, of which eight studies on appendicitis and two studies on peritonitis. Moderate-quality evidence showed that the use of IOPL with saline was not associated with a reduced risk of mortality (0% vs. 1.1%; RR, 0.31 [95% CI, 0.02-6.39]), intra-abdominal abscess (12.3% vs. 11.8%; RR, 1.02 [95% CI, 0.70-1.48]; I2 = 24%), incisional surgical site infections (3.3% vs. 3.8%; RR, 0.72 [95% CI, 0.18-2.86]; I2 = 50%), postoperative complication (11.0% vs. 13.2%; RR, 0.74 [95% CI, 0.39-1.41]; I2 = 64%), reoperation (2.9% vs. 1.7%; RR,1.71 [95% CI, 0.74-3.93]; I2 = 0%) and readmission (5.2% vs. 6.6%; RR, 0.95 [95% CI, 0.48-1.87]; I2 = 7%) in patients with appendicitis when compared to non-IOPL. Low-quality evidence showed that the use of IOPL with saline was not associated with a reduced risk of mortality (22.7% vs. 23.3%; RR, 0.97 [95% CI, 0.45-2.09], I2 = 0%) and intra-abdominal abscess (5.1% vs. 5.0%; RR, 1.05 [95% CI, 0.16-6.98], I2 = 0%) in patients with peritonitis when compared to non-IOPL. CONCLUSION: IOPL with saline use in patients with appendicitis was not associated with significantly decreased risk of mortality, intra-abdominal abscess, incisional surgical site infection, postoperative complication, reoperation, and readmission compared with non-IOPL. These findings do not support the routine use of IOPL with saline in patients with appendicitis. The benefits of IOPL for IAI caused by other types of abdominal infections need to be investigated.

Dynamic regulable sodium alginate/poly(γ-glutamic acid) hybrid hydrogels promoted chondrogenic differentiation of stem cells.

Traditional hydrogels often fail to match the dynamic interactions between mechanical and cellular behaviors exhibited by the natural cartilage extracellular matrix. In this research, we constructed a novel hybrid hydrogels system based on sodium alginate and polyglutamic acid. By controlling the grafting rate and concentration of polymer, the gelation time and mechanical strength can be adjusted between range of 8-28 s and 60-144 kPa. By adding microcrystalline cellulose into the system, so that the degradation time was prolonged (125%) and the swelling rate was reduced (470%). Additionally, the presence of hydrazone bonds gives the system some dynamic response characteristics, and the hydrogel exhibits excellent self healing and injectable ability. It was found that the system had positive cytocompatibility (80%), which accelerated regulatory gene expression in cartilage tissue. In conclusion, this injectable hydrogel with self-healing and customizable mechanical strength will have broad application prospects in future biomedical engineering.

Bioinspired mineral-polymeric hybrid hyaluronic acid/poly (γ-glutamic acid) hydrogels as tunable scaffolds for stem cells differentiation.

Aiming at the difficulty of integrated repair of osteochondral tissue, we designed a hybrid hydrogel scaffold that mimicked the microenvironment of osteochondral niches. Besides, the nano-hydroxyapatite (nHAP) was specially introduced into the hydrogel for its natural ability to promote bone regeneration. The hydrogel also exhibited good toughness (7500 KJ/m3), strength (1000 kPa), viscoelasticity, and in vitro cell experiments showed that hydrogels had quite good cytocompatibility (near 100 % viability). The results of the three-dimensional (3D) cell culture also proved that the survival rate of the cells in the hybrid hydrogels doped with nHAP and dispersion were the highest. In vitro RT-qPCR experiments proved that after being cultured in hydrogel scaffolds doped with nHAP, bone mesenchymal stem cells (BMSCs) could express genes related to osteoblasts and chondrocytes. As a result, this hydrogel provides a general for developing alternative materials applicable for stem cells differentiation and even osteochondral tissue engineering.

Biomimetic poly(γ-glutamic acid) hydrogels based on iron (III) ligand coordination for cartilage tissue engineering.

For the problems in the research on differentiation of mesenchymal stem cells (BMSCs), such as poor differentiation tendency and low differentiation efficiency, a novel photo-crosslinked extracellular matrix (ECM) inspired double network hydrogel that composed of poly(γ-glutamic acid) (γ-PGA) hydrogel and Fe3+ ligand coordination was designed and manufactured. Compared with those traditional γ-PGA based hydrogels, the introduction of Fe3+ significantly enhanced the mechanical properties of the hydrogel and accelerated the chondrogenesis efficiency of BMSCs chondrogenesis. The experimental results confirmed that the mechanical properties of hydrogel enhanced by the introduction of metal ions Fe3+ could promote BMSCs proliferation, induce cartilage-specific gene expression, and increase secretion of hydroxyproline (HYP) and glycosaminoglycan (GAG). As a result, this method could promote chondrogenic differentiation of BMSCs, accelerate the regeneration of cartilage, and was prospective to be conducive to the research work of cartilage defect repair. Thus, the mechanically enhanced γ-PGA hydrogel scaffold by Fe3+ could mediate BMSCs differentiation and provide a scientific and theoretical basis for research and development of biomedical materials on cartilage tissue engineering field.

Early Enteral Nutrition Preserves Intestinal Barrier Function through Reducing the Formation of Neutrophil Extracellular Traps (NETs) in Critically Ill Surgical Patients.

BACKGROUND: The gut was suggested as the driver of critical illness and organ injury. Recently, excessive formation of neutrophil extracellular traps (NETs) was associated with mucosal inflammation. Direct investigation of intestinal mucosa is essential to illuminate the potential mechanism of gut barrier in critically ill patients. We hypothesized that early enteral nutrition (EN) could decrease intestinal NETs and maintain the gut barrier. METHODS: Intestinal biopsies were obtained using biopsy forceps from critically ill surgical patients complicated with enterocutaneous fistula. Expressions of tight junction (TJ) proteins, mucosal inflammation, and apoptosis were evaluated. Moreover, NET-associated proteins were evaluated in intestinal specimens of patients by Western blot and immunofluorescence analysis. RESULTS: The intestinal barrier was significantly impaired in critically ill patients receiving early total parenteral nutrition (TPN), evidenced by intestinal villi atrophy, inflammatory infiltration, increased enterocyte apoptosis, and abnormal TJ expressions. Early EN significantly alleviated these intestinal injuries. In addition, we observed increased formation of the NET structure and elevated expressions of NET-associated proteins in intestines of critically ill surgical patients. Early EN was associated with the diminished presence of NETs and reduced expression of NET-associated proteins. Mechanically, analysis of the TLR4 pathway showed a significant increase in TLR4, NFκB, and MAPK signaling in patients receiving TPN when compared to those receiving early EN. CONCLUSION: The intestinal barrier is disrupted in the human gut during critical illness. Our data suggests that an increased NET structure was showed in the gut of critically ill surgical patients, and early EN treatment was associated with the reduction of NET formation and the preservation of mucosal immunity.

Biomaterials and biosensors in intestinal organoid culture, a progress review.

As an emerging technology, intestinal organoids are promising new tools for basic and translational research in gastroenterology. Currently, culture of intestinal organoids relies mostly on a type of tumor-derived scaffolds, namely Matrigel, which may pose tumorigenic risks to organoid implantation. Apart from the traditional detection methods, such as tissue slicing and fluorescence staining, the monitoring of intestinal organoids requires real-time biosensors that can adapt to their three-dimensional dynamic growth patterns. In this review, we summarized the recent advances in developing definite hydrogel scaffolds for intestinal organoid culture and identified key parameters for scaffold design. In addition, classified by different substrate compositions like pH, electrolytes, and functional proteins, we concluded the existing live-imaging biosensors and elucidated their underlying mechanisms. We hope this review enhances the understanding of intestinal organoid culture and provides more practical approaches to investigate them.

Bioinspired poly (γ-glutamic acid) hydrogels for enhanced chondrogenesis of bone marrow-derived mesenchymal stem cells.

While peptide-directed scaffolds now serve as well-established platforms for biomimetic three-dimensional (3D) extracellular matrices (ECM), challenges still remain for chondrogenesis through direct mediation of stem cells. Here, biocompatible poly (γ-glutamic acid) (γ-PGA) hydrogels with robust mechanical properties were developed based on methacrylate-γ-PGA (γ-PGA-GMA) and cysteamine functionalized γ-PGA (γ-PGA-SH) for cartilage regeneration. The γ-PGA hydrogels demonstrated good self-crosslinking property as well as tunability through conjugation between active thiol groups of γ-PGA-SH and methacrylate moieties of γ-PGA-GMA. The mechanical property, porous structure, swelling, and degradation process of the hydrogels could be controlled by adjusting modified γ-PGA polymers component. The rheological behavior and compression test of γ-PGA hydrogels illustrated a wide processing range in addition to superb mechanical properties. These γ-PGA hydrogels showed excellent elasticity as well as toughness, withstanding more than 70% of mechanical strain. Meanwhile, the stress modulus of γ-PGA hydrogels could be up to 749 kPa. We also studied γ-PGA hydrogels as scaffolds for the 3D culture and chondrogenesis differentiation of rabbit bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. In a rabbit auricular cartilage defect model, BMSCs-laden hydrogel effectively promoted chondrogenesis. Based on these findings, biomimetic γ-PGA-based hydrogels hold promising application as favorable scaffold biomaterials for cartilage tissue regeneration.

pH-responsive nanomicelles of poly(ethylene glycol)-poly(ε-caprolactone)-poly(L-histidine) for targeted drug delivery.

Here, a novel pH-responsive block copolymer, poly (ethylene glycol)-poly(ε-caprolactone)-poly(L-histidine) (PEG-PCL-PHis), was synthesized and designed for anti-cancer drug delivery with excellent biocompatible, biodegradable, and strong drug loading efficiency. 1H-NMR, IF-IR, and GPC were used to characterize the structure of the PEG-PCL-PHis copolymer. In addition, the morphology, particle size, Zeta potential, and critical micelle concentration (CMC) of different degree of polymerization were determined by transmission electron microscopy (TEM), dynamic light scattering granulometer (DLS), and fluorescence spectrometer, respectively. The strong affinity between the core of micelles and hydrophobic drug was manifested with 15.09% drug loading content and 84.65% entrapment efficiency. In vitro release of DOX from the block copolymer micelle demonstrated, the PEG-PCL-PHis copolymer micelle has stable and durable drug releasing ability accompanied with pH-sensitivity. From the mechanism of cellular uptake the micelles, the pathway of drug release was captured by confocal laser scanning microscope. These experiments demonstrated the safe delivery for anticancer medicine through this novel copolymer. In conclusion, the PEG-PCL-PHis copolymer micelle has great potential to become a safe drug carrier for cancer chemotherapy.

Bioinspired Anti-digestive Hydrogels Selected by a Simulated Gut Microfluidic Chip for Closing Gastrointestinal Fistula.

The anti-digestive features given to hydrogels can prolong their action time in gut environment; however, these types of hydrogels have rarely been reported. Inspired by indigestibility of dietary fibers, we introduced an injectable covalent hydrogel through photopolymerization of glycidyl methacrylate-modified xanthan. This newly synthesized hydrogel exhibited a specific concentration-dependent porosity, swelling ratio, and stiffness. The intestinal epithelial cells-6 could grow on the surface of the stiffer hydrogel, and achieved their gut barrier functions. A simulated gut microfluidic chip was manufactured to demonstrate the hydrogel's good performance of anti-digestion compared with the current product, fibrin sealant. Furthermore, calcium ions could induce the swelling-shrinking behavior of the hydrogel, which assisted in removing the hydrogels at the proper time so as to avoid the mismatch of hydrogel degradation and tissue regeneration. Therefore, this hydrogel is expected to be an outstanding gut repair material, especially for closing gastrointestinal fistula.