Saponin and Ribosome-Inactivating Protein Synergistically Trigger Lysosome-Dependent Apoptosis by Inhibiting Lysophagy: Potential to Become a New Antitumor Strategy.

The susceptibility of lysosomal membranes in tumor cells to cationic amphiphilic drugs (CADs) enables CADs to induce lysosomal membrane permeabilization (LMP) and trigger lysosome-dependent cell death (LDCD), suggesting a potential antitumor therapeutic approach. However, the existence of intrinsic lysosomal damage response mechanisms limits the display of the pharmacological activity of CADs. In this study, we report that low concentrations of QS-21, a saponin with cationic amphiphilicity extracted from Quillaja Saponaria tree, can induce LMP but has nontoxicity to tumor cells. QS-21 and MAP30, a type I ribosome-inactivating protein, synergistically induce apoptosis in tumor cells at low concentrations of both. Mechanistically, QS-21-induced LMP helps MAP30 escape from endosomes or lysosomes and subsequently enter the endoplasmic reticulum, where MAP30 downregulates the expression of autophagy-associated LC3 proteins, thereby inhibiting lysophagy. The inhibition of lysophagy results in the impaired clearance of damaged lysosomes, leading to the leakage of massive lysosomal contents such as cathepsins into the cytoplasm, ultimately triggering LDCD. In summary, our study showed that coadministration of QS-21 and MAP30 amplified the lysosomal disruption and can be a new synergistic LDCD-based antitumor therapy.

Evaluation of the feeding safety of Moringa (Moringa oleifera L.) in the Sprague Dawley rat.

This study aimed to evaluate the safety of Moringa by comparing the effects of different gavage doses of Moringa. The general behavior, body weight, food intake, blood indexes, serum biochemical indexes, and histopathology of rats were used to determine the safety threshold and to provide a reference for the further development and use of Moringa as animal feed. 40 Sprague Dawley rats were selected and given transoral gavage for 28 consecutive days. The T1, T2 and T3 groups were observed for general behavior, body weight, and food intake. Blood and serum biochemical indices were quantified, and histopathology was performed to evaluate the effect and safety of Moringa. The results of the toxicological test showed that (1) Only T1 groups experienced diarrhea. (2) The body weight and food intake of rats in each group were normal compared with the control group. (3) The hematological and serum biochemical indices of rats in the T1 group were significantly different from those of CK but were in the normal range; (4) The results of microscopic examination of the heart, liver, spleen, lung, and kidney of rats in each group were normal, but inflammation occurred in stomach and jejunum of rats in the T1 group, but not in the ileum. The gastrointestinal tract of rats in the T2 and T3 groups were normal. (5) No abnormal death occurred in any of the treatment groups.The results of this study revealed that gavage of Moringa homogenate at a dose of 6 g/kg BW can cause diarrhea in rats. Although there is no pathological effect on weight, food intake, blood and serum biochemical indicators in rats, there are pathological textures in the gastrointestinal tissue caused by diarrhea. Therefore, the safety threshold of Moringa homogenate should be ≤ 3 g/kg BW.

Clinical biomarkers for thyroid immune-related adverse events in patients with stage III and IV gastrointestinal tumors.

Background: Thyroid immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) treatment appear to correlate with a better prognosis. We aimed to investigate clinical biomarkers associated with thyroid irAEs. Methods: We retrospectively analyzed data from 129 patients receiving programmed cell death protein 1 (PD-1) inhibitors for stage III and IV gastrointestinal tumors. Patients were divided into two groups: "thyroid irAEs" group and "no thyroid irAEs" group. We compared continuous variables using Mann-Whitney U and Kruskal-Wallis tests and categorical variables using Pearson's chi-square test. Survival curves were generated using the Kaplan-Meier method, and associations between clinical features and thyroid irAEs were assessed using univariate and multivariate logistic regression models. Associations for thyroid irAEs and outcomes [progression-free survival (PFS), overall survival (OS)] of the patients were performed with a Cox proportional hazard model. Results: A total of 129 patients, including 66 gastric cancer, 30 esophageal squamous cell carcinoma, and 33 hepatocellular carcinoma (HCC), were involved in this analysis with 47 cases of thyroid irAEs occurrence. The Cox proportional hazard model analysis confirmed the extended PFS [hazard rate (HR) = 0.447, 95% confidence interval (CI): 0.215 to 0.931, p = 0.031] and OS (HR = 0.424, 95% CI: 0.201 to 0.893, p = 0.024) for thyroid irAEs group when compared with those of the no thyroid irAEs group. Association between thyroid irAEs and clinical characteristics at baseline was analyzed subsequently by univariate analysis. Higher body mass index (p = 0.005), increased eosinophil count (p = 0.014), increased lactate dehydrogenase (p = 0.008), higher baseline thyroid stimulating hormone (TSH) (p = 0.001), HCC (p = 0.001) and increased adenosine deaminase (ADA) (p = 0.001) were linked with thyroid irAEs occurrence. The multivariable logistic regression model indicated that ADA [odds rate (OR) = 4.756, 95% CI: 1.147 to 19.729, p = 0.032] was independently associated with thyroid irAEs occurrence. Conclusions: Increased baseline level of ADA was associated with thyroid irAEs occurrence in patients with advanced gastrointestinal tumors who received ICI treatment. In the case of abnormal ADA, attention should be paid to the risk of thyroid irAEs.

Toward morphologically relevant extracellular matrix: nanofiber-hydrogel composites for tumor cell culture.

The natural extracellular matrix (ECM) consists of a continuous integrated fibrin network and a negatively charged proteoglycan-based matrix. In this work, we report a novel three-dimensional nanofiber hydrogel composite that mimics the natural ECM structure, exhibiting both degradability and mechanical characteristics comparable to that of tumor tissue. The embedded nanofiber improves the hydrogel mechanical properties, and varying the fiber density can match the elastic modulus of different tumor tissues (1.51-10.77 kPa). The degradability of the scaffold gives sufficient space for tumor cells to secrete and remodel the ECM. The expression levels of cancer stem cell markers confirmed the development of aggressive and metastatic phenotypes of prostate cancer cells in the 3D scaffold. Similar results were obtained in terms of anticancer resistance of prostate cancer cells in 3D scaffolds showing stem cell-like properties, suggesting that the current bionic 3D scaffold tumor model has broad potential in the development of effective targeted agents.

ASCT2-Targeting Antibody-Drug Conjugate MEDI7247 in Adult Patients with Relapsed/Refractory Hematological Malignancies: A First-in-Human, Phase 1 Study.

BACKGROUND: MEDI7247 is a first-in-class antibody-drug conjugate (ADC) consisting of an anti-sodium-dependent alanine-serine-cysteine transporter 2 antibody-conjugated to a pyrrolobenzodiazepine dimer. OBJECTIVE: This first-in-human phase 1 trial evaluated MEDI7247 in patients with hematological malignancies. PATIENTS AND METHODS: Adults with acute myeloid leukemia (AML), multiple myeloma (MM), or diffuse large B-cell lymphoma (DLBCL) relapsed or refractory (R/R) to standard therapies, or for whom no standard therapy exists, were eligible. Primary endpoints were safety and determination of the maximum tolerated dose (MTD). Secondary endpoints included assessments of antitumor activity, pharmacokinetics (PK), and immunogenicity. RESULTS: As of 26 March 2020, 67 patients were treated (AML: n = 27; MM: n = 18; DLBCL: n = 22). The most common MEDI7247-related adverse events (AEs) were thrombocytopenia (41.8%), neutropenia (35.8%), and anemia (28.4%). The most common treatment-related grade 3/4 AEs were thrombocytopenia (38.8%), neutropenia (34.3%), and anemia (22.4%). Anticancer activity (number of responders/total patients evaluated) was observed in 11/67 (16.4%) patients. No correlation was observed between ASCT2 expression and clinical response. Between-patient variability of systemic exposure of MEDI7247 ADC and total antibody were high (AUCinf geometric CV%: 62.3-134.2, and 74.8-126.1, respectively). SG3199 (PBD dimer) plasma concentrations were below the limit of quantification for all patients after Study Day 8. Anti-drug antibody (ADA) prevalence was 7.7%, ADA incidence was 1.9%, and persistent-positive ADA was 5.8%. CONCLUSIONS: Thrombocytopenia and neutropenia limited repeat dosing. Although limited clinical activity was detected, the dose-escalation phase was stopped early without establishing an MTD. The study was registered with ClinicalTrials.gov (NCT03106428).

Janus Membranes Patch Achieves High-Quality Tendon Repair: Inhibiting Exogenous Healing and Promoting Endogenous Healing.

The imbalance between endogenous and exogenous healing is the fundamental reason for the poor tendon healing. In this study, a Janus patch was developed to promote endogenous healing and inhibit exogenous healing, leading to improved tendon repair. The upper layer of the patch is a poly(dl-lactide-co-glycolide)/polycaprolactone (PLGA/PCL) nanomembrane (PMCP-NM) modified with poly(2-methylacryloxyethyl phosphocholine) (PMPC), which created a lubricated and antifouling surface, preventing cell invasion and mechanical activation. The lower layer is a PLGA/PCL fiber membrane loaded with fibrin (Fb) (Fb-NM), serving as a temporary chemotactic scaffold to regulate the regenerative microenvironment. In vitro, the Janus patch effectively reduced 92.41% cell adhesion and 79.89% motion friction. In vivo, the patch inhibited tendon adhesion through the TGF-ß/Smad signaling pathway and promoted tendon maturation. This Janus patch is expected to provide a practical basis and theoretical guidance for high-quality soft tissue repair.

Combined skin dilator and titanium mesh application to repair scalp and skull defects: a case report.

We report a case of skin dilator combined with titanium mesh to repair scalp and skull defects. An 18-year-old male with a scalp defect and skull necrosis due to high-voltage electrical burns was admitted to our hospital. In the first stage, the wound was debrided, antibiotics were applied to control the infection, and two skin dilators were embedded under the scalp after debridement. In the second stage, necrotic skull material was removed, the skull defect was repaired using titanium mesh, and the scalp defect was repaired by transferring expanded flaps. The patient was followed up for 6 months, recovering well and achieving a satisfactory head shape.

Curcumin inhibits prostate cancer by upregulating miR-483-3p and inhibiting UBE2C.

Prostate cancer (PCa) is an extremely common genitourinary malignancy among elderly men. Many evidence have shown the efficacy of curcumin (CUR) in inhibiting the progression of PCa. However, the pharmacological function of CUR in PCa is still not quite clear. In this research, CUR was found to suppress the proliferation and enhance the apoptotic rate in in vitro PCa cell models in a dose- and time-dependent manner. In a xenograft animal model, the administration of CUR contributed to a significant decrease in the growth of the xenograft tumor induced by the transplanted PC-3 cells. Ubiquitin-conjugating enzyme E2 C is implicated in the modulation of multiple types of cancers. In humans, the expression levels of UBE2C are significantly higher in PCa versus benign prostatic hyperplasia. Treatment with CUR decreased the expression of UBE2C, whereas it increased miR-483-3p expression. In contrast with the control mice, the CUR-treated mice showed a significant reduction in UBE2C and Ki-67 in PCa cells. The capability of proliferation, migration, and invasion of PCa cells was inhibited by the knockdown of UBE2C mediated by siRNA. Furthermore, dual luciferase reporter gene assay indicated the binding of miR-483-3p to UBE2C. In summary, CUR exerts its antitumor effects through regulation of the miR-483-3p/UBE2C axis by decreasing UBE2C and increasing miR-483-3p. The findings may also provide new molecular markers for PCa diagnosis and treatment.

A Nucleic Acid-Based LYTAC Plus Platform to Simultaneously Mediate Disease-Driven Protein Downregulation.

Protein degradation techniques, such as proteolysis-targeting chimeras (PROTACs) and lysosome-targeting chimeras (LYTACs), have emerged as promising therapeutic strategies for the treatment of diseases. However, the efficacy of current protein degradation methods still needs to be improved to address the complex mechanisms underlying diseases. Herein, a LYTAC Plus hydrogel engineered is proposed by nucleic acid self-assembly, which integrates a gene silencing motif into a LYTAC construct to enhance its therapeutic potential. As a proof-of-concept study, vascular endothelial growth factor receptor (VEGFR)-binding peptides and mannose-6 phosphate (M6P) moieties into a self-assembled nucleic acid hydrogel are introduced, enabling its LYTAC capability. Small interference RNAs (siRNAs) is then employed that target the angiopoietin-2 (ANG-2) gene as cross-linkers for hydrogel formation, giving the final LYTAC Plus hydrogel gene silencing ability. With dual functionalities, the LYTAC Plus hydrogel demonstrated effectiveness in simultaneously reducing the levels of VEGFR-2 and ANG-2 both in vitro and in vivo, as well as in improving therapeutic outcomes in treating neovascular age-related macular degeneration in a mouse model. As a general material platform, the LYTAC Plus hydrogel may possess great potential for the treatment of various diseases and warrant further investigation.

Enantioselective synthesis of [4]helicenes by organocatalyzed intermolecular C-H amination.

Catalytic asymmetric synthesis of helically chiral molecules has remained an outstanding challenge and witnessed fairly limited progress in the past decades. Current methods to construct such compounds almost entirely rely on catalytic enantiocontrolled fused-ring system extension. Herein, we report a direct terminal peri-functionalization strategy, which allows for efficient assembling of 1,12-disubstituted [4]carbohelicenes via an organocatalyzed enantioselective amination reaction of 2-hydroxybenzo[c]phenanthrene derivates with diazodicarboxamides. The key feature of this approach is that the stereochemical information of the catalyst could be transferred into not only the helix sense but also the remote C-N axial chirality of the products, thus enabling the synthesis of [4]- and [5]helicenes with both structural diversity and stereochemical complexity in good efficiency and excellent enantiocontrol. Besides, the large-scale preparations and representative transformations of the helical products further demonstrate the practicality of this protocol. Moreover, DFT calculations reveal that both the hydrogen bonds and the C-H---π interactions between the substrates and catalyst contribute to the ideal stereochemical control.

Improving combination cancer immunotherapy by manipulating dual immunomodulatory signals with enzyme-triggered, cell-penetrating peptide-mediated biomodulators.

Immunosuppressive tumor microenvironments challenge the effectiveness of protein-based biopharmaceuticals in cancer immunotherapy. Reestablishing tumor cell immunogenicity by enhancing calreticulin (CRT) exposure is expected to improve tumor immunotherapy. Given that CRT translocation is inherently modulated by phosphorylated eIF2α, the selective inhibition of protein phosphatase 1 (PP1) emerges as an effective strategy to augment tumor immunogenicity. To harness the PP1-disrupting potential of GADD34-derived motifs and address their limited intracellular delivery, we integrated these sequences into an enzyme-triggered, cell-penetrating peptide-mediated chimeric protein scaffold. This design not only facilitates efficient cytoplasmic delivery of these immunostimulatory motifs to induce "eat-me" signaling, but also provides a versatile platform for combination immunotherapy. Fabrication of biomodulators with cytotoxic BLF1 provides additional "eat-me" signaling through phosphatidylserine exposure or that with an immunomodulatory designed ankyrin repeat protein disables "don't-find-me" signaling by antagonizing PD-L1. Notably, these bifunctional biomodulators exhibit remarkable ability to induce macrophage phagocytosis, dendritic cell maturation, and CD8+ T activation, ultimately substantially inhibiting tumor growth. This study presents a modular genetic coding strategy for PP1-centered therapies that enables seamless integration of immunostimulatory sequences into protein-based anti-tumor cocktail therapies, thereby offering novel alternatives for improving antitumor efficacy.

Spider-Silk-like Fiber Mat-Covered Polypropylene Warp-Knitted Hernia Mesh for Inhibition of Fibrosis under Dynamic Environment.

Hernia surgery is a widely performed procedure, and the use of a polypropylene mesh is considered the standard approach. However, the mesh often leads to complications, including the development of scar tissue that wraps around the mesh and causes it to shrink. Consequently, there is a need to investigate the relationship between the mesh and scar formation as well as to develop a hernia mesh that can prevent fibrosis. In this study, three different commercial polypropylene hernia meshes were examined to explore the connection between the fabric structure and mechanical properties. In vitro dynamic culture was used to investigate the mechanism by which the mechanical properties of the mesh in a dynamic environment affect cell differentiation. Additionally, electrospinning was employed to create polycaprolactone spider-silk-like fiber mats to achieve mechanical energy dissipation in dynamic conditions. These fiber mats were then combined with the preferred hernia mesh. The results demonstrated that the composite mesh could reduce the activation of fibroblast mechanical signaling pathways and inhibit its differentiation into myofibroblasts in dynamic environments.

In Situ Vaccination with An Injectable Nucleic Acid Hydrogel for Synergistic Cancer Immunotherapy.

Recently, therapeutic cancer vaccines have emerged as promising candidates for cancer immunotherapy. Nevertheless, their efficacies are frequently impeded by challenges including inadequate antigen encapsulation, insufficient immune activation, and immunosuppressive tumor microenvironment. Herein, we report a three-in-one hydrogel assembled by nucleic acids (NAs) that can serve as a vaccine to in situ trigger strong immune response against cancer. Through site-specifically grafting the chemodrug, 7-ethyl-10-hydroxycamptothecin (also known as SN38), onto three component phosphorothioate (PS) DNA strands, a Y-shaped motif (Y-motif) with sticky ends is self-assembled, at one terminus of which an unmethylated cytosine-phosphate-guanine (CpG) segment is introduced as an immune agonist. Thereafter, programmed cell death ligand-1 (PD-L1) siRNA that performs as immune checkpoint inhibitor is designed as a crosslinker to assemble with the CpG- and SN38-containing Y-motif, resulting in the formation of final NA hydrogel vaccine. With three functional agents inside, the hydrogel can remarkably induce the immunogenic cell death to enhance the antigen presentation, promoting the dendritic cell maturation and effector T lymphocyte infiltration, as well as relieving the immunosuppressive tumor environment. When inoculated twice at tumor sites, the vaccine demonstrates a substantial antitumor effect in melanoma mouse model, proving its potential as a general platform for synergistic cancer immunotherapy.

Micro-nano hierarchical scaffold providing temporal-matched biological constraints for tendon reconstruction.

Due to the limitations of tendon biology, high-quality tendon repair remains a clinical and scientific challenge. Here, a micro-nano hierarchical scaffold is developed to promote orderly tendon regeneration by providing temporal-matched biological constraints. In short, fibrin (Fb), which provides biological constraints, is loaded into poly (DL-lactide-co-glycolide) nanoyarns with suitable degradation cycles (Fb-loaded nanofiber yarns (Fb-NY)). Then further combined with braiding technology, temporary chemotactic Fb scaffolds with tendon extracellular matrix-like structures are obtained to initiate the regeneration process. At the early stage of healing (2 w), the regeneration microenvironment is regulated (inducing M2 macrophages and restoring the early blood supply necessary for healing) by Fb, and the alignment of cells and collagen is induced by nanoyarn. At the late healing stage (8 w), with the degradation of Fb-NY, non-functional vascular regression occurs, and the newborn tissues gradually undergo load-bearing remodeling, restoring the anvascularous and ordered structure of the tendon. In summary, the proposed repair strategy provides temporal-matched biological constraints, offering a potential pathway to reconstruct the ordered structure and function of tendons.

Shish-kebab structure fiber with nano and micro diameter regulate macrophage polarization for anti-inflammatory and bone differentiation.

Biopolymer grafts often have limited biocompatibility, triggering excessive inflammatory responses similar to foreign bodies. Macrophage phenotype shifts are pivotal in the inflammatory response and graft success. The effects of the morphology and physical attributes of the material itself on macrophage polarization should be the focus. In this study, we prepared electrospun fibers with diverse diameters and formed a shish-kebab (SK) structure on the material surface by solution-induced crystallization, forming electrospun fiber scaffolds with diverse pore sizes and roughness. In vitro cell culture experiments demonstrated that SK structure fibers could regulate macrophage differentiation toward M2 phenotype, and the results of in vitro simulation of in vivo tissue reconstruction by the microenvironment demonstrated that the paracrine role of M2 phenotype macrophages could promote bone marrow mesenchymal stem cells (BMSCs) to differentiate into osteoblasts. In rats implanted with a subcutaneous SK-structured fiber scaffold, the large-pore size and low-stiffness SK fiber scaffolds demonstrated superior immune performance, less macrophage aggregation, and easier differentiation to the anti-inflammatory M2 phenotype. Large pore sizes and low-stiffness SK fiber scaffolds guide the morphological design of biological scaffolds implanted in vivo, which is expected to be an effective strategy for reducing inflammation when applied to graft materials in clinical settings.

Improving nanochemoimmunotherapy efficacy by boosting "eat-me" signaling and downregulating "don't-eat-me" signaling with Ganoderma lucidum polysaccharide-based drug delivery.

To address the challenges posed by low immunogenicity and immune checkpoints during cancer treatment, we propose an alternative strategy that combines immunogenic cell death (ICD) effects with CD47/SIRPα blockade to reactivate phagocytosis of tumor cells by macrophages with polysaccharide-based drug delivery. In this study, the EGFR inhibitor gefitinib was identified as a novel CD47 modulator, which promoted the translocation of CD47 molecules from the cell membrane to endosomes through the EGFR-Rab5 pathway, leading to reduced cell surface CD47 levels and limiting interaction with SIRPα. Based on this finding, we developed prophagocytic mixed nanodrugs to enhance macrophage phagocytosis by encapsulating ICD inducer doxorubicin and CD47 inhibitor gefitinib with immunostimulatory polysaccharides from Ganoderma lucidum. This approach downregulated cell surface CD47 expression to attenuate "don't-eat-me" signaling, while increasing doxorubicin accumulation in tumors by inhibiting drug-resistance proteins, leading to more exposure of calreticulin and amplifying the "eat-me" signaling. In vivo experiments demonstrated that this approach significantly suppressed intraperitoneal tumor dissemination, reversed doxorubicin-induced weight loss, and effectively induced macrophage polarization, dendritic cell maturation, and CD8+ T cell activation. These findings highlighted the significant potential of our macrophage-centered therapeutic strategy using polysaccharide-based nanocarriers and provided new perspectives for chemoimmunotherapy.

Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: ClinicalTrail.gov NCT05782192.

Cobweb-Inspired Micro/Nanostructured Scaffolds for Soft Tissue Regeneration with Inhibition Effect of Fibrosis under Dynamic Environment.

In soft tissue repair, fibrosis can lead to repair failure and long-term chronic pain in patients. Excessive mechanical stimulation of fibroblasts is one of the causes of fibrosis during abdominal wall regeneration. Inspired by the cobweb, a polycaprolactone beaded fiber is prepared by electrospinning. The cobweb-inspired structure attenuates the mechanical stimulation of cells under a dynamic environment. Nano-protrusions are introduced into the scaffold for further inhibition of fibrosis by self-induced crystallization. A machine is built for in vitro dynamic culture and rat abdominal subcutaneous embedding experiments are performed to verify the inhibiting effect of fibrosis in a dynamic environment in vivo. Results show that the expression of integrin ß1 and α-smooth muscle actin is inhibited by the cobweb-inspired structure under dynamic culture. The results of hematoxylin and eosin and Masson's trichrome indicate that the cobweb-inspired structure has a good inhibitory effect on fibrosis in a dynamic environment in vivo. In general, the cobweb-inspired scaffold with nano-protrusions has a good ability to inhibit fibrosis under both static and dynamic environments. It is believed that the scaffold has promising applications in the field of inhibiting fibrosis caused by mechanical stimulation.

A multifunctional surgical suture with electroactivity assisted by oligochitosan/gelatin-tannic acid for promoting skin wound healing and controlling scar proliferation.

Surgical wound closure is accomplished most frequently with sutures, optimally proceeding rapidly and without complication. However, surgical sutures can trigger foreign body reactions and incite abnormal collagen deposition. Sustained inflammation can result in abnormal wound healing with hypertrophic scar formation. Therefore, evolution of suture material to inhibit inflammation and scar formation is of great clinical significance. In the present study, commercial 3-0 PPDO [poly(p-dioxanone)] suture was used as the base material and modified by adding two layers: a drug-loaded layer and an electroactive layer. The former layer was curcumin (Cur) encapsulated by PLGA [poly (lactic-co-glycolic acid)] and the latter layer was composed of oligochitosan-gelatin/tannic acid/polypyrrole (OCS-GE/TA/PPy). The multifunctional sutures, named S@LC@CGTP, had desirable sustained-drug release properties in vitro where Cur could be released for 8 days due to the action of PLGA. The three-dimensional network structure of OCS-GE/TA ensured S@LC@CGTP against surface cracking and maintained electrical. Furthermore, using an in vivo experiment, S@LC@CGTP could attenuate inflammation and promote scar-free wound healing according to suppression of infiltrating inflammatory cells, down-regulation of TGF-ß1 and collagen type I expression, and improved collagen arrangement. Cumulatively, we indicated that S@LC@CGTP suture material has great potential to facilitate optimal, nearly scarless healing of surgical incisions.

Fabrication and in vitro investigation of hyperbranched poly-lysine-grafted warp knitted polypropylene sling for potential treatment of stress urinary incontinence.

Polypropylene (PP) sling implantation is the most commonly performed procedure for women with stress urinary incontinence (SUI). However, concerns have arisen regarding complications caused by slings, including the common issue of erosion, which can be attributed to various factors such as the body's response and bacterial contamination. To address these concerns, we have developed a rectangular mesh self-locking edge sling with a large pore size and lightweight design. Promising results have been obtained from preliminary in vivo mechanical reliability tests, including uniaxial tensile tests. In comparative in vitro fixed load tensile tests and simulated Tension-free Vaginal Tape (TVT) and Transobturator Vaginal Tape inside-out (TVT-O) technique tests using commercial slings, our sling demonstrated less transverse wrinkling. Both slings achieved an effective porosity of over 45% under the TVT technique. However, the commercial sling experienced a significant reduction in effective porosity during the TVT-O technique, whereas our sling maintained a stable effective porosity with minimal wrinkling. Furthermore, we successfully developed cationic hydration rejection-driven antibacterial-anti-fouling coatings on the surface of our sling by grafting hyperbranched poly-lysine (HBPL) mediated by polynorepinephrine. The HBPL coating imparts a positive charge and hydrophilicity to the sling, resulting in elevated bactericidal activity and reducing protein adhesion. An optimal grafting concentration of 20 mg mL-1 was selected, confirming the stability and biocompatibility of the sling coating. This coating is expected to reduce the likelihood of postoperative erosion. Overall, our research represents significant advancements in improving the safety and performance of PP slings for stress urinary incontinence, potentially leading to a reduction in complications following surgery.