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Hedgehog (Hh) signalling regulates hepatic fibrogenesis. MicroRNAs (miRNAs) mediate various cellular processes; however, their role in liver fibrosis is unclear. Here we investigate regulation of miRNAs in chronically damaged fibrotic liver. MiRNA profiling shows that expression of miR-378 family members (miR-378a-3p, miR-378b and miR-378d) declines in carbon tetrachloride (CCl4)-treated compared with corn-oil-treated mice. Overexpression of miR-378a-3p, directly targeting Gli3 in activated hepatic stellate cells (HSCs), reduces expression of Gli3 and profibrotic genes but induces gfap, the inactivation marker of HSCs, in CCl4-treated liver. Smo blocks transcriptional expression of miR-378a-3p by activating the p65 subunit of nuclear factor-κB (NF-κB). The hepatic level of miR-378a-3p is inversely correlated with the expression of Gli3 in tumour and non-tumour tissues in human hepatocellular carcinoma. Our results demonstrate that miR-378a-3p suppresses activation of HSCs by targeting Gli3 and its expression is regulated by Smo-dependent NF-κB signalling, suggesting miR-378a-3p has therapeutic potential for liver fibrosis.

The combination of multiple physiological (swelling, porosity, mechanical, and biodegradation) and biological (cell/tissue-adhesive, cell proliferation, and hemostatic) properties on a single hydrogel has great potential for skin tissue engineering. Adhesive hydrogels based on polydopamine (PDA) have become the most popular in the biomedical field; however, integrating multiple properties on a single adhesive hydrogel remains a challenge. Here, inspired by the chemistry of mussels, we developed PDA–sodium alginate–polyacrylamide (PDA–SA–PAM)-based hydrogels with multiple physiological and biological properties for skin tissue engineering applications. The hydrogels were prepared by alkali-induced polymerization of DA followed by complexation with SA in PAM networks. The chemical composition of the hydrogels was characterized by X-ray photoelectron spectroscopy. PDA–SA complexed chains were homogeneously dispersed in the PAM network and exhibited good elasticity and excellent mechanical properties, such as a compressive stress of 0.24 MPa at a compression strain of 70% for 0.4PDA–SA–PAM. The adhesive hydrogel also maintained a highly interconnected porous structure (∼94% porosity) along with PDA microfibrils. The hydrogel possesses outstanding swelling and biodegradability properties. Owing to the presence of the PDA–SA complex in the PAM network, the hydrogels show good adhesion to various substrates (plastic, skin, glass, computer screens, and leaves); for example, the adhesive strength of the 0.4PDA–SA–PAM to porcine skin was 24.5 kPa. The adhesive component of the PDA–SA chains in the PAM network significantly improves the cell proliferation, cell attachment, cell spreading, and functional expression of human skin fibroblasts (CCD-986sk) and keratinocytes. Moreover, the PDA chains exhibited good hemostatic properties, resulting in rapid blood coagulation. Considering their excellent cell affinity, and rapid blood coagulation ability, these mussel-inspired hydrogels have substantial potential for skin tissue engineering applications.

Poly(vinyl caprolactam) (PNVCL) is one of the most important thermoresponsive polymers because it is similar to poly(N-isopropyl acrylamide). PNVCL precipitates from aqueous solutions in a physiological temperature range (32–34 °C). The use of PNVCL instead of PNIPAM is considered advantageous because of the assumed lower toxicity of PNVCL. PNVCL copolymer gels are sensitive to external stimuli, such as temperature and pH; which gives them a wide range of biomedical applications and consequently attracts considerable scientific interest. This review focuses on the recent studies on PNVCL-based stimuli responsive three dimensional hydrogels (macro, micro, and nano) for biomedical applications. This review also covers the future outlooks of PNVCL-based gels for biomedical applications, particularly in the drug delivery field.

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