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Both of the surface topographical features and distribution of biochemical cues can influence the cell-substrate interactions and thereby tissue regeneration in vivo. However, they have not been combined simultaneously onto a biodegradable scaffold to demonstrate the synergistic role so far. In this study, a proof-of-concept study is performed to prepare micropatterns and peptide gradient on the inner wall of a poly (D,L-lactide-co-caprolactone) (PLCL) guidance conduit and its advantages in regeneration of peripheral nerve in vivo. After linear ridges/grooves of 20/40 μm in width are created on the PLCL film, its surface is aminolyzed in a kinetically controlled manner to obtain the continuous gradient of amino groups, which are then transferred to CQAASIKVAV peptide density gradient via covalent coupling of glutaraldehyde. The Schwann cells are better aligned along with the stripes, and show a faster migration rate toward the region of higher peptide density. Implantation of the nerve guidance conduit made of the PLCL film having both the micropatterns and peptide gradient can significantly accelerate the regeneration of sciatic nerve in terms of rate, function recovery and microstructures, and reduction of fibrosis in muscle tissues. Moreover, this nerve conduit can also benefit the M2 polarization of macrophages and promote vascularization in vivo., Graphical abstract Dual gradient of nerve-affinitive CQAASIKVAV peptides and linear ridges/grooves on the inner surface of biodegradable guidance conduit synergistically promote the regeneration of sciatic nerve in terms of rate, function recovery and microstructures, and reduction of fibrosis in muscle tissues in vivo.Image 1, Highlights • CQAASIKVAV peptide gradient and micropatterns are integrated on inner surface of a nerve regeneration conduit. • Cell alignment and migration are promoted toward the region of a higher peptide density. • The peptide gradient and micropatterns can synergistically accelerate the regeneration of sciatic nerve in vivo.

Emergent and long-term hemorrhage control is requisite and beneficial for reducing global mortality and postoperative complications (e.g., second bleeding and adverse tissue adhesion). Despite recent advance in injectable hydrogels for hemostasis, achieving rapid gelation, strong tissue-adhesive property and stable mechanical strength under fluid physiological environment is still challenging. Herein, we developed a novel chitosan hydrogel (CCS@gel) via dynamic Schiff base reaction and mussel-inspired catechol chemistry. The hydrogel possessed high gelation rate (10 s), strong wet adhesiveness, excellent self-healing performance and biocompatibility. More importantly, the CCS@gel exhibited saline-induced contractile performance and mechanical enhancement, promoting its mechanical property in moist internal conditions. In vivo studies demonstrated its superior hemostatic efficacy for diverse anticoagulated visceral and carotid bleeding scenarios, compared to commercialized fibrin glue. The hydrogel-treated rats survived for 8 weeks with minimal inflammation and postoperative adhesion. These results revealed that the promising CCS@gel would be a facile, efficient and safe sealant for clinical hemorrhage control.

Background: Hepatocellular carcinoma (HCC) is a common solid tumor worldwide with a very poor prognosis. Identifying more specific and sensitive HCC biomarkers remains an urgent need for its early diagnosis and treatment. Methods: Total RNAs from paired HBV-derived HCC tumors and adjacent peritumor tissues (APTs) were amplified and subjected to RNA sequencing analysis, and differentially expressed genes (DEGs) between tumors and APTs were selected and verified. Findings: 166 DEGs were identified, and remarkably, eight top-ranked and verified DEGs (TK1, CTTN, CEP72, TRIP13, FTH1, FLAD1, CHRM2, AMBP) all contained putative OCT4 binding motifs at their promoter regions. TK1, TRIP13 and OCT4 were exemplified to have concurrent higher expression in HCC tumors than in APTs, and OCT4 proteins were bound to the promoters of both genes in vitro and in vivo. Knocking out OCT4 gene in hepatoma cell lines reduced the expression of TK1 and TRIP13 and significantly dampened their tumorigenicity. Interpretation: We identified multiple novel HCC signature genes that may serve as promising biomarkers for HCC diagnosis and prognosis. Their common transcriptional regulation by OCT4 implicates its key roles in the occurrence and development of HCC, and thus positions OCT4 as a potential therapeutic target for treating HCC. Funding Statement: This work was supported by grants from the National Key Research and Development Program of China (grant numbers 2016YFA0101201, 2016YFA0100303), the National Natural Science Foundation of China (grant number 31601103), the National High Technology Research and Development Program of China (grant number 2012AA020204) and the Fundamental Research Funds for the Central Universities (grant number WK9110000023). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: All studies on mice were conducted in accordance with the National Institute Guide for the Care and Use of Laboratory Animal. The animal protocol has been approved by the Committee of the Ethics of Animal Experiments, Zhejiang University.