The occurrence and development mechanisms of esophageal stricture: state of the art review.

BACKGROUND: Esophageal strictures significantly impair patient quality of life and present a therapeutic challenge, particularly due to the high recurrence post-ESD/EMR. Current treatments manage symptoms rather than addressing the disease's etiology. This review concentrates on the mechanisms of esophageal stricture formation and recurrence, seeking to highlight areas for potential therapeutic intervention. METHODS: A literature search was conducted through PUBMED using search terms: esophageal stricture, mucosal resection, submucosal dissection. Relevant articles were identified through manual review with reference lists reviewed for additional articles. RESULTS: Preclinical studies and data from animal studies suggest that the mechanisms that may lead to esophageal stricture include overdifferentiation of fibroblasts, inflammatory response that is not healed in time, impaired epithelial barrier function, and multimethod factors leading to it. Dysfunction of the epithelial barrier may be the initiating mechanism for esophageal stricture. Achieving perfect in-epithelialization by tissue-engineered fabrication of cell patches has been shown to be effective in the treatment and prevention of esophageal strictures. CONCLUSION: The development of esophageal stricture involves three stages: structural damage to the esophageal epithelial barrier (EEB), chronic inflammation, and severe fibrosis, in which dysfunction or damage to the EEB is the initiating mechanism leading to esophageal stricture. Re-epithelialization is essential for the treatment and prevention of esophageal stricture. This information will help clinicians or scientists to develop effective techniques to treat esophageal stricture in the future.

A nomogram model based on SII, AFR, and NLR to predict infectious complications of laparoscopic hysterectomy for cervical cancer.

BACKGROUND: This study aimed to investigate the potential risk factors associated with postoperative infectious complications following laparoscopic hysterectomy for cervical cancer and to develop a prediction model based on these factors. METHODS: This study enrolled patients who underwent selective laparoscopic hysterectomy for cervical cancer between 2019 and 2024. A multivariate regression analysis was performed to identify independent risk factors associated with postoperative infectious complications. A nomogram prediction model was subsequently constructed and evaluated using R software. RESULTS: Out of 301 patients were enrolled and 38 patients (12.6%) experienced infectious complications within one month postoperatively. Six variables were independent risk factors for postoperative infectious complications: age ≥ 60 (OR: 3.06, 95% confidence interval (CI): 1.06-8.79, P = 0.038), body mass index (BMI) ≥ 24.0 (OR: 3.70, 95%CI: 1.4-9.26, P = 0.005), diabetes (OR: 2.91, 95% CI: 1.10-7.73, P = 0.032), systemic immune-inflammation index (SII) ≥ 830 (OR: 6.95, 95% CI: 2.53-19.07, P < 0.001), albumin-to-fibrinogen ratio (AFR) < 9.25 (OR: 4.94, 95% CI: 2.02-12.07, P < 0.001), and neutrophil-to-lymphocyte ratio (NLR) ≥ 3.45 (OR: 7.53, 95% CI: 3.04-18.62, P < 0.001). Receiver operator characteristic (ROC) curve analysis indicated an area under the curve (AUC) of this nomogram model of 0.928, a sensitivity of 81.0%, and a specificity of 92.1%. CONCLUSIONS: The nomogram model, incorporating age, BMI, diabetes, SII, AFR, and NLR, demonstrated strong predictive capabilities for postoperative infectious complications following laparoscopic hysterectomy for cervical cancer.

Stem-loop RT-qPCR system for multiplex miRNA profiling and its application in wound healing-specific biomarker identification.

MiRNAs are biomarkers widely used in research but their clinical application is still challenging due to their low expression levels. Current methods for miRNA detection involve separate transcription and quantification for each target, which is costly and unsuitable for large sample sizes. This study provides a strategy for designing and screening miRNA-specific stem-loop reverse transcription (RT) primers, which enable the simultaneous transcription of three miRNAs and U6, and the concurrent detection of miRNA and U6 in the same transcript using TaqMan probes labeled with different dyes. The strategy was successfully employed to establish multiplex RT-PCR and dual-quantitative PCR (qPCR) quantification systems for 21 differentially expressed miRNAs during wound healing. The corresponding system can accurately quantify the cell culture samples containing miR-7a-5p mimic, miR-7a-5p inhibitor, or negative control. In summary, our results demonstrate that this strategy could efficiently accomplish the design, screening, and analysis of stem-loop RT primers for multiplex miRNA detection. Compared with the commercially customized miRNA assay kits, our system showed a higher degree of automation, more accurate qPCR assay capabilities, and lower assay costs, which could provide practical value for clinical diagnosis.

Designer broad-spectrum polyimidazolium antibiotics.

For a myriad of different reasons most antimicrobial peptides (AMPs) have failed to reach clinical application. Different AMPs have different shortcomings including but not limited to toxicity issues, potency, limited spectrum of activity, or reduced activity in situ. We synthesized several cationic peptide mimics, main-chain cationic polyimidazoliums (PIMs), and discovered that, although select PIMs show little acute mammalian cell toxicity, they are potent broad-spectrum antibiotics with activity against even pan-antibiotic-resistant gram-positive and gram-negative bacteria, and mycobacteria. We selected PIM1, a particularly potent PIM, for mechanistic studies. Our experiments indicate PIM1 binds bacterial cell membranes by hydrophobic and electrostatic interactions, enters cells, and ultimately kills bacteria. Unlike cationic AMPs, such as colistin (CST), PIM1 does not permeabilize cell membranes. We show that a membrane electric potential is required for PIM1 activity. In laboratory evolution experiments with the gram-positive Staphylococcus aureus we obtained PIM1-resistant isolates most of which had menaquinone mutations, and we found that a site-directed menaquinone mutation also conferred PIM1 resistance. In similar experiments with the gram-negative pathogen Pseudomonas aeruginosa, PIM1-resistant mutants did not emerge. Although PIM1 was efficacious as a topical agent, intraperitoneal administration of PIM1 in mice showed some toxicity. We synthesized a PIM1 derivative, PIM1D, which is less hydrophobic than PIM1. PIM1D did not show evidence of toxicity but retained antibacterial activity and showed efficacy in murine sepsis infections. Our evidence indicates the PIMs have potential as candidates for development of new drugs for treatment of pan-resistant bacterial infections.

Biologic Mechanisms of Macrophage Phenotypes Responding to Infection and the Novel Therapies to Moderate Inflammation.

Pro-inflammatory and anti-inflammatory types are the main phenotypes of the macrophage, which are commonly notified as M1 and M2, respectively. The alteration of macrophage phenotypes and the progression of inflammation are intimately associated; both phenotypes usually coexist throughout the whole inflammation stage, involving the transduction of intracellular signals and the secretion of extracellular cytokines. This paper aims to address the interaction of macrophages and surrounding cells and tissues with inflammation-related diseases and clarify the crosstalk of signal pathways relevant to the phenotypic metamorphosis of macrophages. On these bases, some novel therapeutic methods are proposed for regulating inflammation through monitoring the transition of macrophage phenotypes so as to prevent the negative effects of antibiotic drugs utilized in the long term in the clinic. This information will be quite beneficial for the diagnosis and treatment of inflammation-related diseases like pneumonia and other disorders involving macrophages.

VDVM: An automatic vertebrae detection and vertebral segment matching framework for C-arm X-ray image identification.

BACKGROUND: C-arm fluoroscopy, as an effective diagnosis and treatment method for spine surgery, can help doctors perform surgery procedures more precisely. In clinical surgery, the surgeon often determines the specific surgical location by comparing C-arm X-ray images with digital radiography (DR) images. However, this heavily relies on the doctor's experience. OBJECTIVE: In this study, we design a framework for automatic vertebrae detection as well as vertebral segment matching (VDVM) for the identification of vertebrae in C-arm X-ray images. METHODS: The proposed VDVM framework is mainly divided into two parts: vertebra detection and vertebra matching. In the first part, a data preprocessing method is used to improve the image quality of C-arm X-ray images and DR images. The YOLOv3 model is then used to detect the vertebrae, and the vertebral regions are extracted based on their position. In the second part, the Mobile-Unet model is first used to segment the vertebrae contour of the C-arm X-ray image and DR image based on vertebral regions respectively. The inclination angle of the contour is then calculated using the minimum bounding rectangle and corrected accordingly. Finally, a multi-vertebra strategy is applied to measure the visual information fidelity for the vertebral region, and the vertebrae are matched based on the measured results. RESULTS: We use 382 C-arm X-ray images and 203 full length X-ray images to train the vertebra detection model, and achieve a mAP of 0.87 in the test dataset of 31 C-arm X-ray images and 0.96 in the test dataset of 31 lumbar DR images. Finally, we achieve a vertebral segment matching accuracy of 0.733 on 31 C-arm X-ray images. CONCLUSIONS: A VDVM framework is proposed, which performs well for the detection of vertebrae and achieves good results in vertebral segment matching.

A predictive nomogram model for postoperative delirium in elderly patients following laparoscopic surgery for gynecologic cancers.

BACKGROUND: This study aimed to investigate potential risk factors associated with postoperative delirium (POD) in elderly patients following laparoscopic surgery for gynecologic cancers and construct a nomogram predictive model based on these factors. METHODS: Eligible elderly patients who underwent laparoscopic surgery for gynecologic cancers were enrolled and grouped according to the development of POD within postoperative 7 days. Potential risk factors were assessed by the univariate and multivariate logistic regression analyses. A nomogram model was constructed based on these factors and evaluated by R. RESULTS: A total of 226 elderly patients were enrolled in the final data analysis and 39 patients had suffered POD with an incidence of 17.3%. Older age, modified frailty index (mFI) ≥ 0.225, C-reactive protein (CRP) ≥ 8.0, systemic immune-inflammation index (SII), and albumin/fibrinogen ratio (AFR) were five independent risk factors for POD by univariate and multivariate analyses. The area under the curve (AUC) of the constructed nomogram model based on these five factors was 0.833. CONCLUSIONS: The constructed nomogram model based on age, CRP, SII, mFI, and AFR could effectively predict POD in elderly patients with gynecologic cancers.

Mitochondria-Targeting Polymer Micelles in Stepwise Response Releasing Gemcitabine and Destroying the Mitochondria and Nucleus for Combined Antitumor Chemotherapy.

Mitochondrial DNA and nuclear DNA are essential genetic material which play an important role in maintaining normal metabolism, survival, and proliferation of cells. Constructing a mitochondria-targeting stimuli-responsive nano-drug delivery system releasing chemotherapeutic agents in a stepwise response manner and destroying mitochondrial DNA and nuclear DNA simultaneously is an effective way to improve the anti-tumor effect of chemotherapeutic agents. In this study, a new mitochondria-targeting pH/ROS dual-responsive block copolymer TPP-PEG2k-b-(BS-AA)n (P1), untargeted pH/ROS dual-responsive copolymer mPEG2k-b-(BS-AA)n (P2), pH single-responsive copolymer (mPEG2k-b-(AH-AA)n (P3), ROS single-responsive copolymer mPEG2k-b-(SA-TG)n (P4), and non-responsive copolymer mPEG-b-PCL (P5) were constructed. pH/ROS-responsive properties were characterized by proton nuclear magnetic resonance (1H NMR) and dynamic light scattering (DLS). Anticancer chemotherapeutic agent gemcitabine (GEM) or fluorescent substance Nile Red (NR) were loaded in the polymer micelles. Results of the mitochondrial colocalization experiment indicate that (5-carboxypentyl)(triphenyl)phosphonium bromide (TPP)-functionalized P1 micelles could be efficiently targeted and located in mitochondria. Results of the cellular uptake experiment showed that pH/ROS dual-responsive GEM-loaded P1 and P2 micelles have faster internalized and entry nucleus rates than single-responsive or non-responsive GEM-loaded micelles. The in vitro release experiment suggests pH/ROS dual-responsive GEM/P1 and GEM/P2 micelles have higher cumulative release than single-responsive GEM/P3 and GEM/P4 micelles. The in vitro cytotoxic experiment shows that the mitochondria-targeted dual-responsive GEM/P1 micelles had the lowest IC50 values, and the cytotoxic effect of dual-responsive GEM/P2 micelles was superior to the single-responsive and non-responsive drug-loaded micelles.

High performance benzene vapor sensor based on three-dimensional photonic crystals of zeolitic imidazolate framework-8@graphene quantum dots.

Superior sensitive, selective, and repeatable real-time detection of low concentrations of benzene vapor is vitally important for environmental protection and human health. A benzene vapor sensor using three-dimensional photonic crystals (3-D PCs) based on zeolitic imidazolate framework-8@graphene quantum dots (ZIF-8@GQDs) was proposed. The 3-D PCs were acquired by centrifuging ZIF-8@GQDs pseudo-solutions, which were prepared via hydrothermal methods. The application of the ZIF-8@GQDs 3-D PCs sensor for optical benzene vapor detection via the strong π-π stacking interactions and large specific surface area and abundant open-framework structure of the ZIF-8@GQDs was investigated. The ZIF-8@GQDs 3-D PCs sensor exhibits a more sensitive response to benzene vapor compared with the ZIF-8 3-D PCs sensor. The relationship between the wavelength shift and the benzene vapor concentration was demonstrated to be linear. Additionally, the ZIF-8@GQDs 3-D PCs sensor presents a fast optical response and recovery times of 1 s and 7 s for 200 ppm benzene vapor detection, the benzene vapor detection limit can reach 1 ppm, and the deviation of the reflected wavelength varied within 2 nm after 10 cycles. Moreover, the fabricated ZIF-8@GQDs 3-D PCs sensor exhibited reliability and exceptional thermal and long-time storage stability, demonstrating great potential for practical benzene vapor sensing applications.

A Glycosylated Cationic Block Poly(ß-peptide) Reverses Intrinsic Antibiotic Resistance in All ESKAPE Gram-Negative Bacteria.

Carbapenem-resistant Gram-negative bacteria (GNB) are heading the list of pathogens for which antibiotics are the most critically needed. Many antibiotics are either unable to penetrate the outer-membrane or are excluded by efflux mechanisms. Here, we report a cationic block ß-peptide (PAS8-b-PDM12) that reverses intrinsic antibiotic resistance in GNB by two distinct mechanisms of action. PAS8-b-PDM12 does not only compromise the integrity of the bacterial outer-membrane, it also deactivates efflux pump systems by dissipating the transmembrane electrochemical potential. As a result, PAS8-b-PDM12 sensitizes carbapenem- and colistin-resistant GNB to multiple antibiotics in vitro and in vivo. The ß-peptide allows the perfect alternation of cationic versus hydrophobic side chains, representing a significant improvement over previous antimicrobial α-peptides sensitizing agents. Together, our results indicate that it is technically possible for a single adjuvant to reverse innate antibiotic resistance in all pathogenic GNB of the ESKAPE group, including those resistant to last resort antibiotics.

Photothermal Microfluidic Sensing Platform Using Near-Infrared Laser-Driven Multiplexed Dual-Mode Visual Quantitative Readout.

The application of different sensing principles in microfluidic devices opens up further possibilities for the development of point-of-care testing (POCT). Herein, the photothermal sensing principle is introduced in microfluidic paper-based analytical devices (µPADs) to develop a photothermal microfluidic sensing platform using near-infrared (NIR) laser-driven multiplexed dual-mode visual quantitative readout. Prussian blue (PB) as the analyte-associated photothermal agent was in situ synthesized in thermoresponsive poly(N-isopropylacrylamide) hydrogels to serve as the on-chip photothermal sensing element. The NIR laser-driven photothermal effect of PB triggered not only on-chip dose-dependent heat generation but also phase transition-induced dye release from the hydrogels, simultaneously enabling both thermal image- and distance-based dual-mode visual quantitative readout of the analyte concentration in a multiplexed manner. Both the on-chip temperature elevation value of the hydrogels and the traveling distance of released dye solutions were proportional to the concentration of PB. With the detection of silver ions in environmental water as a proof-of-concept study, the photothermal µPAD can detect silver ions at a concentration as low as 0.25 µM with high selectivity and satisfactory accuracy. The photothermal microfluidic sensing platform holds great potential for POCT with promising integratability and broad applicability, owing to the combination of synergistic advantages of the photothermal sensing principle, µPADs, and photothermally responsive hydrogels.

[Fabrication of hydrophilic medical catheter with hydrogel grafting and the in vivo evaluation of its histo-compatibility].

The biocompatible hydrogel was fabricated under suitable conditions with natural dextran and polyethylene glycol (PEG) as the reaction materials. The oligomer (Dex-AI) was firstly synthesized with dextran and allylisocyanate (AI). This Dex-AI was then reacted with poly (ethyleneglycoldiacrylate) (PEGDA) under the mass ratio of 4∶6 to get hydrogel (DP) with the maximum water absorption of 810%. This hydrogel was grafted onto the surface of medical catheter via diphenyl ketone treatment under ultraviolet (UV) initiator. The surface contact angle became lower from (97 ± 6.1)° to (25 ± 4.2)° after the catheter surface was grafted with hydrogel DP, which suggests that the catheter possesses super hydrophilicity with hydrogel grafting. The in vivo evaluation after they were implanted into ICR rats subcutaneously verified that this catheter had less serious inflammation and possessed better histocompatibility comparing with the untreated medical catheter. Therefore, it could be concluded that hydrogel grafting is a good technology for patients to reduce inflammation due to catheter implantation, esp. for the case of retention in body for a relative long time.

Hyaluronic acid (HA)-based hydrogels for full-thickness wound repairing and skin regeneration.

In this work, two kinds of hyaluronic acid (HA)-based hydrogels were fabricated: one is made from physical freezing-thawing of HA solution (HA1), and the other is from chemical cross-linking of HA and polysaccharide (HA2). They were applied to repair full-thickness skin defects with New Zealand rabbits as the test animals, using powder HA and cotton dress as the references. The wound starts to heal after wounds were disinfected with iodine followed by coating with HA2, HA1, HA and cotton dress (the control), respectively. They were recorded as 4 treatments (groups), HA2, HA1, HA and the control. The healing progress was followed and tested in the duration of 56 days, and the biological repairing mechanism was explored. From the wound area alteration, white blood cell (WBC) measurements and H&E staining, HA2 was the most promising treatment in promoting the wound healing with least serious scar formation. Immunochemistry analyses and real-time PCR tests of the bio-factors involved in the wound healing, vascular endothelial growth factor (VEGF), alpha-smooth muscle actin (α-SMA) and transforming growth factor beta-1 (TGF-ß1), exhibited that HA2 enhanced VEGF and α-SMA secretion but reduced TGF-ß1 expression at early stage, which alleviated the wound inflammation, improved the skin regeneration and relieved the scar formation.

Radix Puerariae and Fructus Crataegi mixture inhibits renal injury in type 2 diabetes via decreasing of AKT/PI3K.

BACKGROUND: Radix puerariae (RP) is a herbal medicines for diabetes, mainly because of anti-oxidative, insulin resistance and hypoglycemic effect. Fructus crataegi (FC) also possesses strong antioxidant activity in vitro. This study focused on the effects of herbal mixture of RP and FC (RPFC) on renal protection through a diabetic rat model. METHODS: Type 2 Diabetic model was established with high fat diet followed by injecting rats a low dose of STZ (25 mg/kg body weight). Rats were randomly divided into five groups: normal, high fat diet, diabetes mellitus, high fat diet plus RPFC prevention, and RPFC prevention before diabetes mellitus. RPFC was given to rats daily by intragastric gavage. The blood bio-chemical index and renal pathological changes were examined. The later includes hematoxylin and eosin staining, periodic acid schiff staining, and Masson trichrome staining. Protein levels of were determined by Western blot and immunohistochemical staining. mRNA levels were detected by RT-PCR. RESULTS: Rats prevented with RPFC resulted in decreasing blood glucose with corresponding vehicle treated rats. Glomerulus mesangial matrix expansion, renal capsule constriction, and renal tubular epithelial cell edema were less severe following RPFC prevention. Moreover, RPFC prevention reduced protein levels of PI3K, AKT, α-SMA and collagen IV in the kidney of diabetic rats. CONCLUSION: Combined prevention with RPFC may inhibit the PI3K/AKT pathway in the kidney, thereby prevent renal injury in diabetic rats.

Synthesis, characterization and cytocompatibility of a degradable polymer using ferric catalyst for esophageal tissue engineering.

This study focused on the synthesis, characterization and cytocompatibility of a biodegradable polymer by the cross-linking from poly(ethylene glycol-co-lactide) dimethacrylate (PLEGDMA), polyethylene glycol diacrylate (PEGDA) and N-isopropylacrylamide, where PLEGDMA was synthesized by ring-opening oligomerization of poly(ethylene glycol) with different molecular weights (Mn = 400, 600, 1000, 2000 Da) and L-lactide using low toxic iron(III) acetylacetonate (Fe(acac)3) as the catalyst and subsequently being terminated with dimethacrylate. The product, PLEGDMA, was analyzed to confirm its chemistry using FTIR spectroscopy, (1)H NMR spectra and gel permeation chromatography etc. The thermodynamic properties, mechanical behaviors, surface hydrophilicity, degradability and cytotoxicity of the cross-linked product were evaluated by differential scanning calorimetry, tensile tests, contact angle measurements and cell cultures. The effects of reaction variables such as PEGDA content and reactants ratio were optimized to achieve a material with low glass transition temperature (Tg), high wettability and preferable mechanical characteristics. Using a tubular mould which has been patented in our group, a tubular scaffold with predetermined dimension and pattern was fabricated, which aims at guiding the growth and phenotype regulation of esophageal primary cells like fibroblast and smooth muscle cell towards fabricating tissue engineered esophagus in future.

[Research on the preparation and optical absorption properties of two-dimensional ZnO array].

The present paper's main work is firstly preparing a single layer and a large area polystyrene microspheres mask, with 117, 350 and 500 nm in diameter, and then depositing a layer of zinc oxide thin film on the mask board by RF magnetron sputtering technique, using nanospheres lithography technique to remove the polystyrene spheres by soaking with tetrahydrofuran, and two-dimensional zinc oxide nano-array samples were obtained at last. The samples were characterized on the morphology and composition by scanning electron microscopy and energy dispersive X-ray spectrometer. The results showed that the samples are zinc oxide nanocluster formed by ordered cellular reticular structures. By measuring with absorption spectroscopy in the range from 300 to 800 nm at room temperature, the absorption peak turns up with broadening and red shift with the increase in the diameter of polystyrene colloidal spheres, namely the nano-particles diameters. As the sputtering time increases, that is, the increase in the zinc oxide film thickness, the light absorption rate increases. In addition, theoretical calculation based on the theory of discrete dipole approximation was performed to simulate the optical absorption properties of the zinc oxide nanocluster arrays between 300 and 800 nm. Dipole approximation theory can be used to calculate the absorption of the particles of any shape and size. Currently, the theoretical calculation results of various shapes of nanostructured metals such as gold and silver are consist ent with the experimental results. But the application of the theory of discrete dipole approximation calculation of ZnO nanoparticles was rarely reported. In this paper, this theory has been used to calculate the optical absorption properties of triangle-shaped ZnO nanoparticles array. Light absorption characteristics were simulated according to changes in the dielectric constant and thickness of zinc oxide films, and the results can be used to explain the experimental results.

Axial assembly of AuNR for tumor theranostics via Zn2+-GSH chelation induced degradation of AuNR@ZIF-8 heterostructures.

Tumor microenvironment responsive photothermal ablation is a noninvasive and accurately targeted approach for cancer therapy. Herein, an intracellular directional assembly strategy for enhanced photothermal therapy (PTT) was realized by using ZIF-8 encapsulated Au nanorod (AuNR) heterostructure as the precursor of photothermal convertible material. The ZIF-8 shell selectively degraded in tumor cells upon the chelation between GSH and Zn2+, while the as-formed Zn(SG) connected the released AuNR in end-to-end fashion. The coating of ZIF-8 shell significantly improves the stability and targeting of AuNR, and the released Zn2+ shielded the GSH binding site on the lateral side of AuNR, increased the plasmonic coupling efficiency of AuNR assembly geometer. This design enabled atomic-economical, efficient and low-side effect targeted photothermal therapy through the effective integration of heterostructures.

Construction methods and biomedical applications of PVA-based hydrogels.

Polyvinyl alcohol (PVA) hydrogel is favored by researchers due to its good biocompatibility, high mechanical strength, low friction coefficient, and suitable water content. The widely distributed hydroxyl side chains on the PVA molecule allow the hydrogels to be branched with various functional groups. By improving the synthesis method and changing the hydrogel structure, PVA-based hydrogels can obtain excellent cytocompatibility, flexibility, electrical conductivity, viscoelasticity, and antimicrobial properties, representing a good candidate for articular cartilage restoration, electronic skin, wound dressing, and other fields. This review introduces various preparation methods of PVA-based hydrogels and their wide applications in the biomedical field.

Cation-crosslinkedκ-carrageenan sub-microgel medium for high-quality embedded bioprinting.

Three-dimensional (3D) bioprinting embedded within a microgel bath has emerged as a promising strategy for creating intricate biomimetic scaffolds. However, it remains a great challenge to construct tissue-scale structures with high resolution by using embedded 3D bioprinting due to the large particle size and polydispersity of the microgel medium, as well as its limited cytocompatibility. To address these issues, novel uniform sub-microgels of cell-friendly cationic-crosslinked kappa-carrageenan (κ-Car) are developed through an easy-to-operate mechanical grinding strategy. Theseκ-Car sub-microgels maintain a uniform submicron size of around 642 nm and display a rapid jamming-unjamming transition within 5 s, along with excellent shear-thinning and self-healing properties, which are critical for the high resolution and fidelity in the construction of tissue architecture via embedded 3D bioprinting. Utilizing this new sub-microgel medium, various intricate 3D tissue and organ structures, including the heart, lungs, trachea, branched vasculature, kidney, auricle, nose, and liver, are successfully fabricated with delicate fine structures and high shape fidelity. Moreover, the bone marrow mesenchymal stem cells encapsulated within the printed constructs exhibit remarkable viability exceeding 92.1% and robust growth. Thisκ-Car sub-microgel medium offers an innovative avenue for achieving high-quality embedded bioprinting, facilitating the fabrication of functional biological constructs with biomimetic structural organizations.

Bioprinted biomimetic hydrogel matrices guiding stem cell aggregates for enhanced chondrogenesis and cartilage regeneration.

Articular cartilage tissue has limited self-repair capabilities, with damage frequently progressing to irreversible degeneration. Engineered tissues constructed through bioprinting and embedded with stem cell aggregates offer promising therapeutic alternatives. Aggregates of bone marrow mesenchymal stromal cells (BMSCs) demonstrate enhanced and more rapid chondrogenic differentiation than isolated cells, thus facilitating cartilage repair. However, it remains a key challenge to precisely control biochemical microenvironments to regulate cellular adhesion and cohesion within bioprinted matrices simultaneously. Herein, this work reports a bioprintable hydrogel matrix with high cellular adhesion and aggregation properties for cartilage repair. The hydrogel comprises an enhanced cell-adhesive gelatin methacrylate and a cell-cohesive chitosan methacrylate (CHMA), both of which are subjected to photo-initiated crosslinking. By precisely adjusting the CHMA content, the mechanical stability and biochemical cues of the hydrogels are finely tuned to promote cellular aggregation, chondrogenic differentiation and cartilage repair implantation. Multi-layer constructs encapsulated with BMSCs, with high cell viability reaching 91.1%, are bioprinted and photo-crosslinked to support chondrogenic differentiation for 21 days. BMSCs rapidly form aggregates and display efficient chondrogenic differentiation both on the hydrogels and within bioprinted constructs, as evidenced by the upregulated expression of Sox9, Aggrecan and Collagen 2a1 genes, along with high protein levels. Transplantation of these BMSC-laden bioprinted hydrogels into cartilaginous defects demonstrates effective hyaline cartilage repair. Overall, this cell-responsive hydrogel scaffold holds immense promise for applications in cartilage tissue engineering.