Shape-Memory-Reduced Graphene/Chitosan Cryogels for Non-Compressible Wounds.

In this study, an antibacterial and shape-memory chitosan cryogel with high blood absorption and fast recovery from non-compressible wounds was prepared using a one-step method. Herein, we prepared a shape-memory-reduced graphene/chitosan (rGO-CTS) cryogel using a one-step method with a frozen mixing solution of chitosan, citric acid, dopamine, and graphene oxide, before treating it with alkaline solutions. The alkaline solution not only promoted the double cross-linking of chitosan but also induced dopamine to form polydopamine-reducing graphene oxide. Scanning electron microscope (SEM) images showed that the rGO-CTS cryogel possessed a uniform porous network structure, attributing excellent water-induced shape-memory properties. Moreover, the rGO-CTS cryogel exhibited good mechanical properties, antibacterial activity, and biocompatibility. In mouse liver trauma models, the rGO-CTS cryogel showed good blood clotting and hemostatic capabilities. Therefore, this composite cryogel has great potential as a new hemostatic material for application to non-compressible wounds.

[Efficacy and safety of rituximab in children and adolescents with mature B-cell non-Hodgkin's lymphoma: a Meta analysis]. / 利妥昔单抗治疗儿童及青少年成熟Bç»†èƒžéžéœå¥‡é‡‘æ·‹å·´ç˜¤ç–—æ•ˆåŠå®‰å ¨æ€§çš„Meta分析.

OBJECTIVES: To study the efficacy and safety of rituximab combined with chemotherapy in the treatment of children and adolescents with mature B-cell non-Hodgkin's lymphoma (B-NHL) through a Meta analysis. METHODS: The databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and Weipu were searched to obtain 10 articles on rituximab in the treatment of mature B-NHL in children and adolescents published up to June 2022, with 886 children in total. With 3-year event-free survival (EFS) rate, 3-year overall survival (OS) rate, complete remission rate, mortality rate, and incidence rate of adverse reactions as outcome measures, RevMan 5.4 software was used for Meta analysis, subgroup analysis, sensitivity analysis, and publication bias analysis. RESULTS: The rituximab+chemotherapy group showed significant increases in the 3-year EFS rate (HR=0.38, 95%CI: 0.25-0.59, P<0.001), 3-year OS rate (HR=0.29, 95%CI: 0.14-0.61, P=0.001), and complete remission rate (OR=3.72, 95%CI: 1.89-7.33, P<0.001) as well as a significant reduction in the mortality rate (OR=0.31, 95%CI: 0.17-0.57, P<0.001), as compared with the chemotherapy group without rituximab. There was no significant difference in the incidence rate of adverse reactions between the two groups (OR=1.28, 95%CI: 0.85-1.92, P=0.24). CONCLUSIONS: The addition of rituximab to the treatment regimen for children and adolescents with mature B-cell non-Hodgkin's lymphoma can bring significant survival benefits without increasing the incidence of adverse reactions.

Dynamic Double Cross-Linked Self-Healing Polysaccharide Hydrogel Wound Dressing Based on Schiff Base and Thiol-Alkynone Reactions.

In this study, a hydrogel composite wound dressing with antibacterial and self-healing ability was prepared using cysteine-modified carboxymethyl chitosan, sodium oxidized alginate, and but-3-yn-2-one base on Schiff base and thiol-alkynone double cross-links. The structure and properties of the hydrogel were characterized by scanning electron microscope, Fourier-transform infrared, and rheological test, followed by antibacterial and in vivo biocompatibility tests. The results showed that the hydrogel exhibited good self-healing, mechanical properties, good antibacterial effect, and in vivo biocompatibility, and can inhibit inflammation and promote skin tissue regeneration in mice. This novel self-healing hydrogel dressing has a broad application prospect in skin tissue engineering.

Visible-Light-Driven Antimicrobial Activity and Mechanism of Polydopamine-Reduced Graphene Oxide/BiVO4 Composite.

In this study, a photocatalytic antibacterial composite of polydopamine-reduced graphene oxide (PDA-rGO)/BiVO4 is prepared by a hydrothermal self-polymerization reduction method. Its morphology and physicochemical properties are characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Fourier-transform infrared (FT-IR), and X-ray diffraction (XRD). The results indicate that BiVO4 particles are evenly distributed on the rGO surface. Escherichia coli (E. coli) MG1655 is selected as the model bacteria, and its antibacterial performance is tested by flat colony counting and the MTT method under light irradiation. PDA-rGO/BiVO4 inhibits the growth of E. coli under both light and dark conditions, and light significantly enhances the bacteriostasis of PDA-rGO/BiVO4. A combination of BiVO4 with PDA-rGO is confirmed by the above characterization methods as improving the photothermal performance under visible light irradiation. The composite possesses enhanced photocatalytic antibacterial activity. Additionally, the photocatalytic antibacterial mechanism is investigated via the morphology changes in the SEM images of MG1655 bacteria, 2',7'-dichlorofluorescein diacetate (DCFH-DA), the fluorescence detection of the reactive oxygen species (ROS), and gene expression. These results show that PDA-rGO/BiVO4 can produce more ROS and lead to bacterial death. Subsequently, the q-PCR results show that the transmembrane transport of bacteria is blocked and the respiratory chain is inhibited. This study may provide an important strategy for expanding the application of BiVO4 in biomedicine and studying the photocatalytic antibacterial mechanism.

Tailoring Nano-Porous Surface of Aligned Electrospun Poly (L-Lactic Acid) Fibers for Nerve Tissue Engineering.

Despite the existence of many attempts at nerve tissue engineering, there is no ideal strategy to date for effectively treating defective peripheral nerve tissue. In the present study, well-aligned poly (L-lactic acid) (PLLA) nanofibers with varied nano-porous surface structures were designed within different ambient humidity levels using the stable jet electrospinning (SJES) technique. Nanofibers have the capacity to inhibit bacterial adhesion, especially with respect to Staphylococcus aureus (S. aureus). It was noteworthy to find that the large nano-porous fibers were less detrimentally affected by S. aureus than smaller fibers. Large nano-pores furthermore proved more conducive to the proliferation and differentiation of neural stem cells (NSCs), while small nano-pores were more beneficial to NSC migration. Thus, this study concluded that well-aligned fibers with varied nano-porous surface structures could reduce bacterial colonization and enhance cellular responses, which could be used as promising material in tissue engineering, especially for neuro-regeneration.

Construction of methylation driver gene-related prognostic signature and development of a new prognostic stratification strategy in neuroblastoma.

BACKGROUND: Aberrant DNA methylation is one of the major epigenetic alterations in neuroblastoma. OBJECTIVE: Exploring the prognostic significance of methylation driver genes in neuroblastoma could help to comprehensively assess patient prognosis. METHODS: After identifying methylation driver genes (MDGs), we used the LASSO algorithm and stepwise Cox regression to construct methylation driver gene-related risk score (MDGRS), and evaluated its predictive performance by multiple methods. By combining risk grouping and MDGRS grouping, we developed a new prognostic stratification strategy and explored the intrinsic differences between the different groupings. RESULTS: We identified 44 stably expressed MDGs in neuroblastoma. MDGRS showed superior predictive performance in both internal and external cohorts and was strongly correlated with immune-related scores. MDGRS can be an independent prognostic factor for neuroblastoma, and we constructed the nomogram to facilitate clinical application. Based on the new prognostic stratification strategy, we divided the patients into three groups and found significant differences in overall prognosis, clinical characteristics, and immune infiltration between the different subgroups. CONCLUSION: MDGRS was an accurate and promising tool to facilitate comprehensive pre-treatment assessment. And the new prognostic stratification strategy could be helpful for clinical decision making.

Efficacy and safety of selumetinib in patients with neurofibromatosis type 1 and inoperable plexiform neurofibromas: a systematic review and meta-analysis.

BACKGROUND: The approval of selumetinib in patients with neurofibromatosis type 1(NF1) and inoperable plexiform neurofibromas (PN) has reshaped the landscape of clinical management of the disease, and further comprehensive evaluation of the drug's efficacy and safety is needed. METHODS: Original articles reporting on the efficacy and safety of elumetinib in patients with NF1 were comprehensively searched in the Pubmed database, Embase database, Cochrane Library, and Web of Science database and screened for inclusion of studies that met the criteria. We pooled the objective response rate (ORR), disease control rate (DCR), disease progression rate (DPR), and the rate of improvement in PN-related complications using meta-analysis. The incidence of drug-related adverse events was also statistically analyzed. RESULTS: This study included 10 clinical trials involving 268 patients. The pooled ORR was 68.0% (95% CI 58.0-77.3%), the DCR was 96.8% (95% CI 90.8-99.7%) and the DPR was only 1.4% (95% CI 0-4.3%). The pooled improvement rate was 75.3% (95% CI 56.2-90.9%) for pain and 77.8% (95% CI 63.1-92.5%) for motor disorders. Most adverse events were mild, with the most common being gastrointestinal reactions (diarrhea: 62.5%; vomiting: 54.5%). CONCLUSION: Our study demonstrates that selumetinib is effective in patients with NF1 and PN, significantly improving the serious complications associated with PN as well as having tolerable toxicities. Our findings help to increase clinicians' confidence in applying selumetinib and promote the clinical adoption and benefit of the new drug.

Multiphase enhanced CT-based transformer for differential diagnosis and predicting surgical risk events of solid abdominal tumors in children.

BACKGROUND: For pediatric patients with solid abdominal tumors, early diagnosis can guide clinical treatment decisions, and comprehensive preoperative evaluation is essential to reduce surgical risk. The aim of this study was to explore the feasibility of multiphase enhanced CT-based transformer in the early diagnosis of tumors and prediction of surgical risk events (SRE). METHODS: A total of 496 pediatric patients with solid abdominal tumors were enrolled in the study. With Swin transformer, we constructed and trained two Swin-T models based on preoperative multiphase enhanced CT for personalized prediction of tumor type and SRE status. Subsequently, we comprehensively evaluated the performance of each model and constructed four benchmark models for performance comparison. RESULTS: There was no significant difference in SRE status between tumor types. In the diagnostic task, areas under the receiver operating characteristic curves (AUC) of the Swin-T model were 0.987 (95 % CI, 0.973-0.997) and 0.844 (95 % CI, 0.730-0.940) in the training and validation cohorts, respectively. In predicting SRE, AUCs of the Swin-T model were 0.920 (95 % CI, 0.885-0.948) and 0.741 (95 % CI, 0.632-0.838) in the training and test cohorts, respectively. The Swin-T model achieved the best performance in both classification tasks compared to benchmark models. CONCLUSION: The Swin-T model is a promising tool to assist pediatricians in the differential diagnosis of abdominal tumors and in comprehensive preoperative evaluation.

The causal relationship between gut microbiota and lymphoma: a two-sample Mendelian randomization study.

Background: Previous studies have indicated a potential link between the gut microbiota and lymphoma. However, the exact causal interplay between the two remains an area of ambiguity. Methods: We performed a two-sample Mendelian randomization (MR) analysis to elucidate the causal relationship between gut microbiota and five types of lymphoma. The research drew upon microbiome data from a research project of 14,306 participants and lymphoma data encompassing 324,650 cases. Single-nucleotide polymorphisms were meticulously chosen as instrumental variables according to multiple stringent criteria. Five MR methodologies, including the inverse variance weighted approach, were utilized to assess the direct causal impact between the microbial exposures and lymphoma outcomes. Moreover, sensitivity analyses were carried out to robustly scrutinize and validate the potential presence of heterogeneity and pleiotropy, thereby ensuring the reliability and accuracy. Results: We discerned 38 potential causal associations linking genetic predispositions within the gut microbiome to the development of lymphoma. A few of the more significant results are as follows: Genus Coprobacter (OR = 0.619, 95% CI 0.438-0.873, P = 0.006) demonstrated a potentially protective effect against Hodgkin's lymphoma (HL). Genus Alistipes (OR = 0.473, 95% CI 0.278-0.807, P = 0.006) was a protective factor for diffuse large B-cell lymphoma. Genus Ruminococcaceae (OR = 0.541, 95% CI 0.341-0.857, P = 0.009) exhibited suggestive protective effects against follicular lymphoma. Genus LachnospiraceaeUCG001 (OR = 0.354, 95% CI 0.198-0.631, P = 0.0004) showed protective properties against T/NK cell lymphoma. The Q test indicated an absence of heterogeneity, and the MR-Egger test did not show significant horizontal polytropy. Furthermore, the leave-one-out analysis failed to identify any SNP that exerted a substantial influence on the overall results. Conclusion: Our study elucidates a definitive causal link between gut microbiota and lymphoma development, pinpointing specific microbial taxa with potential causative roles in lymphomagenesis, as well as identifying probiotic candidates that may impact disease progression, which provide new ideas for possible therapeutic approaches to lymphoma and clues to the pathogenesis of lymphoma.

Eggshell membrane powder reinforces adhesive polysaccharide hydrogels for wound repair.

Multifunctional polysaccharide hydrogels with strong tissue adhesion, and antimicrobial and hemostatic properties are attractive wound healing materials. In this study, a chitosan-based hydrogel (HCS) was designed, and its properties were enhanced by incorporating oxidized eggshell membrane (OEM). Hydrogel characterization and testing results showed that the hydrogel had excellent antimicrobial properties, cytocompatibility, satisfactory adhesion properties on common substrates, and wet-state adhesion capacity. A rat liver injury model confirmed the significant hemostatic effect of the hydrogel. Finally, the ability of the hydrogel to promote wound healing was verified using rat skin wound repair experiments. Our findings indicate that HCS/OEM hydrogels with added eggshell membrane fibers have better self-healing properties, mechanical strength, adhesion, hemostatic properties, and biocompatibility than HCS hydrogels, in addition to having superior repair performance in wound repair experiments. Overall, the multifunctional polysaccharide hydrogels fabricated in this study are ideal for wound repair.

Aligned Electroactive Electrospun Fibrous Scaffolds for Peripheral Nerve Regeneration.

Effective repair and functional recovery of large peripheral nerve deficits are urgent clinical needs. A biofunctional electroactive scaffold typically acts as a "bridge" for the repair of large nerve defects. In this study, we constructed a biomimetic piezoelectric and conductive aligned polypyrrole (PPy)/polydopamine (PDA)/poly-l-lactic acid (PLLA) electrospun fibrous scaffold to improve the hydrophilicity and cellular compatibility of PLLA and restore the weakened piezoelectric effect of PDA, which is beneficial in promoting Schwann cell differentiation and dorsal root ganglion neuronal extension and alignment. The aligned PPy/PDA/PLLA fibrous scaffold bridged the sciatic nerve of Sprague-Dawley rats with a 10 mm deficit, prevented autotomy, and promoted nerve regeneration and functional recovery, thereby activating the calcium and AMP-activated protein kinase signaling pathways. Therefore, electroactive fibrous scaffolds exhibit great potential for neural tissue regeneration.

Combining multiple cell death pathway-related risk scores to develop neuroblastoma cell death signature.

PURPOSE: Cell death plays an important role in tumourigenesis and progression; nevertheless, the clinical significance of cell death-related genes in neuroblastoma remains incompletely understood. METHODS: We separately constructed the corresponding risk scores for each of the eight cell death pathways separately and assessed their predictive performance. Through Cox regression analysis, these eight risk scores were integrated to obtain final cell death risk scores (CDRS). We evaluated the predictive performance of CDRS in multiple datasets and compared its accuracy with the clinical characteristics of patients and some existing prognostic models for neuroblastoma. We then explored the differences in immune infiltration between the high and low CDRS groups, and the significance of CDRS on EFS and disease progression. RESULTS: All eight risk scores have high predictive accuracy, with the Immunogenic-RS being the most accurate and the cuproptosis-RS the least accurate. Model genes are mainly enriched in a variety of cancer-related pathways and are closely related to the clinical characteristics. CDRS showed superior and robust predictive performance in multiple datasets and was more accurate than the clinical characteristics of patients and some existing prognostic models for neuroblastoma. High CDRS group featured distinct immune cold tumor profiles and may have poorer immune checkpoint inhibitor efficacy. CDRS had significance in predicting EFS and disease progression. CONCLUSION: We integrated risk scores associated with multiple cell death pathways to develop a high-performing and robust neuroblastoma signature. CDRS was a promising tool that may help with risk assessment and prediction of overall prognosis, and thus improve clinical outcomes.

A Bioinspired Self-Healing Conductive Hydrogel Promoting Peripheral Nerve Regeneration.

The development of self-healing conductive hydrogels is critical in electroactive nerve tissue engineering. Typical conductive materials such as polypyrrole (PPy) are commonly used to fabricate artificial nerve conduits. Moreover, the field of tissue engineering has advanced toward the use of products such as hyaluronic acid (HA) hydrogels. Although HA-modified PPy films are prepared for various biological applications, the cell-matrix interaction mechanisms remain poorly understood; furthermore, there are no reports on HA-modified PPy-injectable self-healing hydrogels for peripheral nerve repair. Therefore, in this study, a self-healing electroconductive hydrogel (HASPy) from HA, cystamine (Cys), and pyrrole-1-propionic acid (Py-COOH), with injectability, biodegradability, biocompatibility, and nerve-regenerative capacity is constructed. The hydrogel directly targets interleukin 17 receptor A (IL-17RA) and promotes the expression of genes and proteins relevant to Schwann cell myelination mainly by activating the interleukin 17 (IL-17) signaling pathway. The hydrogel is injected directly into the rat sciatic nerve-crush injury sites to investigate its capacity for nerve regeneration in vivo and is found to promote functional recovery and remyelination. This study may help in understanding the mechanism of cell-matrix interactions and provide new insights into the potential use of HASPy hydrogel as an advanced scaffold for neural regeneration.

Age-related seroprevalence trajectories of seasonal coronaviruses in children including neonates in Guangzhou, China.

OBJECTIVES: Four seasonal coronaviruses, including human coronavirus (HCoV)-229E and HCoV-OC43, HCoV-NL63, and HCoV-HKU1 cause approximately 15-30% of common colds in adults. However, the full landscape of the immune trajectory to these viruses that covers the whole childhood period is still not well understood. METHODS: We evaluated the serological responses against the four seasonal coronaviruses in 1886 children aged under 18 years by using enzyme-linked immunosorbent assay. The optical density values against each HCoV were determined from each sample. Generalized additive models were constructed to determine the relationship between age and seroprevalence throughout the whole childhood period. The specific antibody levels against the four seasonal coronaviruses were also tested from the plasma samples of 485 pairs of postpartum women and their newborn babies. RESULTS: The immunoglobulin (Ig) G levels of the four seasonal coronaviruses in the mother and the newborn babies were highly correlated (229E: r = 0.63; OC43: r = 0.65; NL63: r = 0.69; HKU1: r = 0.63). The seroprevalences in children showed a similar trajectory in that the levels of IgG in the neonates dropped significantly and reached the lowest level after the age of around 1 year (229E: 1.18 years; OC43: 0.97 years; NL63: 1.01 years; HKU1: 1.02 years) and then resurgence in the children who aged older than 1 year. Using the lowest level from the generalized additive models as our cutoff, the seroprevalences for HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 were 98.11%, 96.23%, 96.23% and 94.34% at the age of 16-18 years. CONCLUSION: Mothers share HCoV-specific IgGs with their newborn babies and the level of maternal IgGs waned at around 1 year after birth. The resurgence of the HCoV-specific IgGs was found thereafter with the increase in age suggesting repeated infection occurred in children.

In situ polydopamine functionalized poly-L-lactic acid nanofibers with near-infrared-triggered antibacterial and reactive oxygen species scavenging capability.

The development of a new multi-functional poly(L)-lactide (PLLA) nanofibrous scaffold with excellent antibacterial and reactive oxygen species (ROS) scavenging capability is quite important in tissue engineering. In this study, polydopamine (PDA)/PLLA nanofibers were prepared by combining electrospinning and post in-situ polymerization. The post in-situ polymerization of PDA on the PLLA nanofiber enable PDA uniformly distribute on PLLA nanofiber surface. PDA/PLLA nanofibrous composites also achieved stronger mechanical strength, hydrophilicity, good oxidation resistance and enhanced near-infrared photothermal effect. The near-infrared photothermal effect from PDA made the PDA/PLLA a good antibacterial material. The in vitro ROS scavenging ability of the PDA made PDA/PLLA be beneficial to damaged tissue repair. These results indicate that PDA/PLLA nanofibrous scaffold can be used as a tissue engineering scaffold material with versatile biomedical applications.

Three-layer core-shell structure of polypyrrole/polydopamine/poly(l-lactide) nanofibers for wound healing application.

Poor wound healing is a very common clinical problem, so far there is no completely satisfactory treatment. Electropsun nanofibrous wound dressings may provide an ideal structure to improve wound healing. Therefore, development of nanofibrous wound dressings with rapid hemostasis, antibacterial and tissue regenerative multi-functions has been a hotspot in the field of skin tissue engineering. In this work, polydopamine (PDA) and polypyrrole (PPy) were uniformly coated onto the surface of poly(l-lactide) (PLLA) nanofibers by in-situ polymerization, forming a novel PPy/PDA/PLLA three-layer core-shell structure. The homogeneously coated PPy and PDA two layers could significantly increase the hydrophilicity, conductivity, near-infrared photothermal antibacterial property, the speed of wound hemostasis, antioxidant capacity and reactive oxygen species (ROS) scavenging capacity, respectively. In addition, PPy/PDA/PLLA nanofibers showed good biocompatibility. Rat wound healing model confirmed that PPy/PDA/PLLA nanofibers could significantly accelerate wound repair in vivo. Thus, this novel nanofibrous wound dressing is a promising candidate for clinical wound healing.

A novel macrolide derivative ameliorates smoke-induced inflammation and emphysema by inhibiting NF-κB activation.

Although inflammation and emphysema in patients with chronic obstructive pulmonary disease (COPD) can be ameliorated by antibiotics such as erythromycin, the impact of drug resistance is still controversial. We aimed to evaluate the role of F528, a new macrolide derivative without antibacterial effect, in cigarette smoke (CS)-induced pulmonary inflammation and emphysema in a mouse model, as well as in a macrophage cell line. The inflammatory cell number and cell type in the BALF were counted, and the levels of cytokines in the BALF and cultured cell medium were measured by ELISA. The degree of emphysema and apoptosis was evaluated by H&E and immunohistochemical staining, respectively. The lung function of the mice was evaluated by a small animal lung function meter. Furthermore, the expression levels of MMP-2, MMP-9, and phospho-NF-κB in the cells and lung tissue were measured by Western blot and qRT-PCR. In the BALF of the CS-induced pulmonary inflammation and emphysema model, the numbers of inflammatory cells and cytokines were significantly decreased after F528 intervention. F528 intervention also significantly protected lung function from CS-induced emphysema, while the mean lining interception (MLI) of the F528-treated CS group was significantly lower than that of the vehicle-treated CS group. In addition, F528 treatment reduced the phosphorylation of NF-κB induced by smoke, and the expression of MMP-2 and MMP-9 was also obviously decreased by F528 treatment. We therefore conclude that F528 reduces cigarette smoke-induced inflammation and emphysema in vivo and in vitro through inhibition of the activation of NF-κB.

Injectable nanofiber-polysaccharide self-healing hydrogels for wound healing.

Injectable self-healing hydrogels of natural polysaccharides that mimic the extracellular matrix to promote cellular growth are attractive materials for wound healing. Here, a novel hydrogel was fabricated based on carboxymethyl chitosan (CS) and aldehyde functionalized sodium alginate via Schiff base reaction. To enhance the hydrogel's properties, carboxymethyl-functionalized polymethyl methacrylate (PMAA) short nanofibers were obtained through sodium hydroxide-treated polymethyl methacrylate nanofibers, and added to a CS solution. Gelation time was determined for different hydrogels including 0-5 mg/mL PMAA short nanofibers. The nanofiber hydrogels were tested for their injectability and self-healing abilities and were demonstrated to be easily injectable with excellent self-healing abilities. Additionally, in vitro cytocompatibility experiments, good interaction between the cultured cells and hydrogels was seen. Further, the polysaccharide hydrogel containing short PMMA nanofibers significantly facilitated wound healing in rats compared with the polysaccharide hydrogel and control groups. Thus, the developed hydrogel has great potential for wound healing applications.

Collagen and chondroitin sulfate functionalized bioinspired fibers for tendon tissue engineering application.

Functional tendon tissue engineering depends on harnessing the biochemical and biophysical cues of the native tendon extracellular matrix. In this study, we fabricated highly-aligned poly(L-lactic acid) (PLLA) fibers with surfaces decorated by two of the crucial tendon ECM components, type 1 collagen (COL1) and chondroitin sulfate (CS), through a coaxial stable jet electrospinning approach. Effects of the biomimetic COL1-CS (shell)/PLLA (core) fibers on the tenogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro were investigated. Higher rates of cell spreading and proliferation are observed on the aligned COL1-CS/PLLA fibers compared to that on the plain PLLA fibers. Expression of the tendon-associated genes scleraxis (SCX) and COL1 as well as protein tenomodulin (TNMD) are significantly increased. Introduction of mechanical stimulation gives rise to synergistic effect on tenogenic differentiation of hMSCs. Higher expression of TGF-ß2, TGFßR-II, and Smad3 by the cells on the COL1-CS/PLLA fiber substrates are observed, which indicates that COL1-CS/PLLA ultrafine fibers dictate the hMSC tenogenic differentiation through activating the TGF-ß signaling pathway. Animal study in rat Achilles tendon repair model corroborated the promoting role of COL1-CS/PLLA in regenerating a tendon-like tissue. Thus, our highly aligned biomimicking fibers may serve as an efficient scaffolding system for functional tendon regeneration.

Preparation and characterization of antibacterial dopamine-functionalized reduced graphene oxide/PLLA composite nanofibers.

Electrospun poly(l)-lactide (PLLA) ultrafine fibers are a biodegradable and biocompatible scaffold, widely used in tissue engineering applications. Unfortunately, these scaffolds have some limitations related to the absence of bioactivity and antibacterial capacity. In this study, dopamine-functionalized reduced graphene oxide (rGO)/PLLA composite nanofibers were fabricated via electrospinning. The morphology and the physicochemical and biological properties of the composite nanofibers were investigated. The results indicate that incorporating rGO improves the hydrophilic, mechanical, and biocompatibility properties of PLLA nanofibers. Tetracycline hydrochloride (TC)-loaded rGO/PLLA composite nanofibers showed better controlled drug release profiles compared to GO/PLLA and PLLA nanofibrous scaffolds. Drug-loaded nanofibrous scaffolds showed significantly improved antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). Additionally, rGO/PLLA composite nanofibers exhibited enhanced cytocompatibility. Thus, it can be concluded that rGO/PLLA composite nanofibers allow the development of multifunctional scaffolds for use in biomedical applications.