No abstract

The application of scaffolding materials is believed to hold enormous potential for tissue regeneration. Despite the widespread application and rapid advance of several tissue-engineered scaffolds such as natural and synthetic polymer-based scaffolds, they have limited repair capacity due to the difficulties in overcoming the immunogenicity, simulating in-vivo microenvironment, and performing mechanical or biochemical properties similar to native organs/tissues. Fortunately, the emergence of decellularized extracellular matrix (dECM) scaffolds provides an attractive way to overcome these hurdles, which mimic an optimal non-immune environment with native three-dimensional structures and various bioactive components. The consequent cell-seeded construct based on dECM scaffolds, especially stem cell-recellularized construct, is considered an ideal choice for regenerating functional organs/tissues. Herein, we review recent developments in dECM scaffolds and put forward perspectives accordingly, with particular focus on the concept and fabrication of decellularized scaffolds, as well as the application of decellularized scaffolds and their combinations with stem cells (recellularized scaffolds) in tissue engineering, including skin, bone, nerve, heart, along with lung, liver and kidney.

A new class of pH-responsive capsules based on metal-phenolic networks (MPNs) for anticancer drug loading, delivery and release is reported. The fabrication of drug-loaded MPN capsules, which is based on the formation of coordination complexes between natural polyphenols and metal ions over a drug-coated template, represents a rapid strategy to engineer robust and versatile drug delivery carriers.

The hyperactivated Wnt/β-catenin signaling acts as a switch to induce epithelial to mesenchymal transition and promote colorectal cancer. However, due to its essential role in gut homeostasis, therapeutic targeting of this pathway has proven challenging. Additionally, IL-6/Stat-3 signaling, activated by microbial translocation through the dysregulated mucosal barrier in colon adenomas, facilitates the adenoma to adenocarcinomas transition. However, inter-dependence between these signaling pathways and key mucosal barrier components in regulating colon tumorigenesis and cancer progression remains unclear. In current study, we have discovered, using a comprehensive investigative regimen, a novel and tissue-specific role of claudin-3, a tight junction integral protein, in inhibiting colon cancer progression by serving as the common rheostat of Stat-3 and Wnt-signaling activation. Loss of claudin-3 also predicted poor patient survival. These findings however contrasted an upregulated claudin-3 expression in other cancer types and implicated role of the epigenetic regulation. Claudin-3-/- mice revealed dedifferentiated and leaky colonic epithelium, and developed invasive adenocarcinoma when subjected to colon cancer. Wnt-signaling hyperactivation, albeit in GSK-3β independent manner, differentiated colon cancer in claudin-3-/- mice versus WT-mice. Claudin-3 loss also upregulated the gp130/IL6/Stat3 signaling in colonic epithelium potentially assisted by infiltrating immune components. Genetic and pharmacological studies confirmed that claudin-3 loss induces Wnt/β-catenin activation, which is further exacerbated by Stat-3-activation and help promote colon cancer. Overall, these novel findings identify claudin-3 as a therapeutic target for inhibiting overactivation of Wnt-signaling to prevent CRC malignancy.