Three-dimensional (3D) cell encapsulation in hydrogel provides superb methods to investigate the biochemical cues in directing cellular fate and behaviors outside the organism, the primary step of which is to establish suitable "blank platform" to mimic and simplify native ECM microenvironment. In this study, zwitterionic starch-based "clickable" hydrogels were fabricated via a "copper- and light- free" Michael-type "thiol-ene" addition reaction between acylated-modified sulfobetaine-derived starch (SB-ST-A) and dithiol-functionalized poly(ethylene glycol) (PEG-SH). By incorporating antifouling SB-ST and PEG, the hydrogel system would be excellently protected from nontarget protein adsorption to act as a "blank platform". The hydrogels could rapidly gel under physiological conditions in less than 7 min. Dynamic rheology experiments suggested the stiffness of the hydrogel was close to the native tissues, and the mechanical properties as well as the gelation times and swelling behaviors could be easily tuned by varying the precursor proportions. The protein and cell adhesion assays demonstrated that the hydrogel surface could effectively resist nonspecific protein and cell adhesion. The degradation study in vitro confirmed that the hydrogel was biodegradable. A549 cells encapsulated in the hydrogel maintained high viability (up to 93%) and started to proliferate in number and extend in morphology after 2 days' culture. These results indicated the hydrogel presented here could be a potential candidate as "blank platform" for 3D cell encapsulation and biochemical cues induced cellular behavior investigation in vitro.

Ti and Ti alloys are bioinert materials and two frequent problems associated with them are bacterial infection and lack of osteogenic potential for rapid bone integration. To overcome the problems, the present study incorporated strontium (Sr) and silver (Ag) simultaneously into porous TiO2 coatings through a single‐step technique, micro‐arc oxidation (MAO). Incorporation of Sr and Ag brought no significant changes to coating micromorphology and physicochemical properties, but endowed TiO2 coatings with both strong antibacterial activity and osteogenic ability. Antibacterial activity increased with Ag contents in the coatings. When Ag content reached 0.58 wt%, the coating showed both excellent short‐term (100.0%) and long‐term (77.6%) antibacterial activities. Sr/Ag‐containing coatings with 18.23 wt% Sr and 0.58 wt% Ag also presented good cytocompatibility for preosteoblast adhesion and proliferation, and promoted preosteoblast osteogenic differentiation both short‐termly and long‐termly. However, higher Ag content (1.29 wt%) showed toxic effects to preosteoblasts. In summary, MAO is a simple and effective way to incorporate Sr and Ag into porous TiO2 coatings and Sr/Ag‐containing TiO2 coating with 18.5 wt% Sr and 0.58 wt% Ag has both good osteogenic activity and strong antibacterial capability short‐termly and long‐termly. Therefore, such coatings are valuable for clinical application to strengthen osseointegration and long‐term high quality use of titanum implants.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1β levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1β fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection.

No abstract

Intraperitoneal adhesions are common and serious complications after surgery. Deposition of proteins and inflammatory response on an injured cecum are the main factors resulting in the formation of adhesion. In this study, purely zwitterionic hydrogels (Z-hydrogels) are developed using thiolated poly­(sulfobetaine methacrylate-co-2-((2-hydroxyethyl)­disulfanyl)­ethyl methacrylate) [poly­(SBMA-co-HDSMA)] as the network backbone and divinyl-functionalized sulfobetaine (BMSAB) as the zwitterionic cross-linker via the thiol–ene click reaction. To improve the anti-inflammatory activity, cefoxitin sodium is loaded into Z-hydrogels (Z/C-hydrogel) to construct the physical barrier/drug system. The gelation time, mechanical behavior, and swelling ratio of the prepared Z-hydrogel can be modulated via adjusting the SBMA/HDSMA ratio in the copolymer. Moreover, they not only exhibit excellent resistance to protein and fibroblast adhesion but also show good biocompatibility and hemocompatibility. To assess its anti-adhesion effects in vivo, the Z-hydrogel is injected on the injured cecum surface using a rat model of sidewall defect-cecum abrasion. The results show that the Z-hydrogel can completely cover the irregular cecum surface and effectively suppress the formation of postoperative adhesion via reducing protein deposition and resisting fibroblast adhesion. Moreover, the introduction of cefoxitin sodium decreases the inflammatory response after surgery, thus further improving the anti-adhesion effect. Overall, we suggest that the Z-hydrogel is a promising candidate for the prevention of a postsurgical peritoneal adhesion.