A composite scaffold was fabricated with a method involving both electrospinning and 3D printing to give microscale pores and good mechanical properties. Biocompatibility and cell infiltration on the scaffold was evaluated by an in vitro study.

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In the study of hollow nerve guidance conduit (NGC), the dispersion of regenerated axons always confused researchers. To address this problem, filler-containing NGC was prepared, which showed better effect in the application of nerve tissue engineering. In this study, nanofiber sponges with abundant macropores, high porosity, and superior compressive strength were fabricated by electrospinning and freeze-drying. Poly(l-lactic acid-co-ε-caprolactone)/silk fibroin (PLCL/SF) nanofiber sponges were used as filler to prepare three-dimensional nanofiber sponges-containing (NS-containing) NGC. In order to study the effect of fillers for nerve regeneration, hollow NGC was set as control. In vitro cell viability studies indicated that the NS-containing NGC could enhance the proliferation of Schwann cells (SCs) due to the macroporous structure. The results of hematoxylin-eosin (HE) and immunofluorescence staining confirmed that SCs infiltrated into the nanofiber sponges. Subsequently, the NS-containing NGC was implanted in a rat sciatic nerve defect model to evaluate the effect in vivo. NS-containing NGC group performed better in nerve function recovery than hollow NGC group. In consideration of the walking track and triceps weight analysis, NS-containing NGC was close to the autograft group. In addition, histological and morphological analyses with HE and toluidine blue (TB) staining, and transmission electron microscope (TEM) were conducted. Better nerve regeneration was observed on NS-containing NGC group both quantitatively and qualitatively. Furthermore, the results of three indexes' immuno-histochemistry and two indexes' immunofluorescence all indicated good nerve regeneration of NS-containing NGC as well, compared with hollow NGC. The results demonstrated NS-containing NGC had great potential in the application of peripheral nerve repair.

No abstract

Achilles tendon rupture prognosis is usually unsatisfactory. After the tendon is injured, it may not function properly because of the fibrotic healing response, which restrains tendon motion. Inflammatory monocytes and tissue-resident macrophages are indispensable regulators in tissue repair, fibrosis, and regeneration. Exosomes from macrophages are crucial factors in tissue microenvironment regulation following tissue injury. This study therefore aimed to clarify the roles of macrophage exosomes in tendon injury (TI) repair. The results show that macrophages play a role after TI. M1 macrophages were increased relative to peritendinous fibrosis after TI. High-throughput sequencing showed abnormal expression of circular RNAs (circRNAs) between exosomes from M2 and M0 macrophages. Among the abnormal expressions of circRNA, circRNA-Ep400 was significantly increased in M2 macrophage exosomes. The results also show that M2 macrophage-derived circRNA-Ep400-containing exosomes are important for promoting peritendinous fibrosis after TI. Bioinformatics and dual-luciferase reporting experiments confirmed that miR-15b-5p and fibroblast growth factor (FGF)-1/7/9 were downstream targets of circRNA-Ep400. High circRNA-Ep400-containing exosome treatment inhibited miR-15b-5p, but promoted FGF1/7/9 expression in both fibroblasts and tenocytes. Furthermore, high circRNA-Ep400-containing exosome treatment promoted fibrosis, proliferation, and migration in both fibroblasts and tenocytes. Taken together, the results show that M2 macrophage-derived circRNA-Ep400-containing exosomes promote peritendinous fibrosis after TI via the miR-15b-5p/FGF-1/7/9 pathway, which suggests novel therapeutics for tendon injury treatment.

Genes related to immune response, inflammatory response and homeostasis presumably have critical roles in RA pathogenesis. Sanguinarine and papaverine have a potential therapeutic effect against RA.

Peripheral nerve injury has seriously affected patient’s health and life. Schwann cells play an important role in peripheral nerve regeneration. However, the effect of the current tissue engineered scaffolds for promoting Schwann cells growth is still not as good as that of autologous graft. In this study, new developed three-dimensional gellan gum/starch (GG/ST) scaffolds with various printing gap for Schwann cells growth were prepared by 3D printing technology. Various physiochemical characterizations of the printed scaffolds were performed including morphology, rheological behavior, swelling ratio, and degradation behavior. The cytotoxicity and biocompatibility of the scaffolds were evaluated using L929 fibroblasts and RSC96 Schwann cells, respectively. The results displayed that the GG/ST scaffold exhibited a porous network structure. The cross-sectional pore density of the hydrogel had a tendency to increase with the ascending printing gap. The swelling rate and degradation rate of the hydrogel gradually increased and eventually reached an equilibrium state. The rheological test results showed that the scaffolds had good printability. MTT cytotoxicity test and CCK-8 cell proliferation test displayed that the scaffold was nontoxic, and Schwann cells could grow well on the scaffold after 5 days of culture, whereas the number of cells on the scaffold with the printing gap of 3 mm was the largest. These results indicated that the GG/ST scaffold prepared by 3D printing technology may have a potential application in peripheral nerve regeneration.

Tendon adhesion formation is associated with the aberrant expression of many genes, and interfering with the expression of these genes can prevent adhesion and promote tendon repair. Recent studies have found that silencing the transforming growth factor β-1 (TGF-β1) gene can reduce the occurrence of tendon adhesions. The development of tissue engineering and three-dimensional (3D) printing technology have provided new solutions for tendon repair. In this study, TGF-β1 gene silencing microRNA (miRNA) based RNAi plasmid was loaded on a 3D tendon scaffold using 3D printing technology. In vitro experiments confirmed the sustained release of plasmid and the good biocompatibility of the printed tendon scaffold. Subsequently, the TGF-β1 gene silencing plasmid loaded tendon scaffold was implanted in a chicken tendon defect model to evaluate the effect of the scaffold in vivo. The results from biomechanical tests and histological examinations showed that the scaffold not only promoted tendon regeneration but also prevented tendon adhesion, which was conducive to the recovery of biofunction. Evaluation of protein expression showed that the loaded plasmids prevented tendon adhesion and promoted tendon functional repair via silencing of the TGF-β1 gene.