Bioinspired and Mechanically Strong Fibers Based on Engineered Non-Spider Chimeric Proteins.

Silk-protein-based fibers have attracted considerable interest due to their low weight and extraordinary mechanical properties. Most studies on fibrous proteins focus on the recombinant spidroins, but these fibers exhibit moderate mechanical performance. Thus, the development of alternative structural proteins for the construction of robust fibers is an attractive goal. Herein, we report a class of biological fibers produced using a designed chimeric protein, which consists of the sequences of a cationic elastin-like polypeptide and a squid ring teeth protein. Remarkably, the chimeric protein fibers exhibit a breaking strength up to about 630 MPa and a corresponding toughness as high as about 130 MJ m-3 , making them superior to many recombinant spider silks and even comparable to some native counterparts. Therefore, this strategy is a novel concept for exploring bioinspired ultrastrong protein materials through the development of new types of structural chimeric proteins.

Cyclosporine A-loaded colon-targeted oral nanomicelles self-assembly by galactosylated carboxymethyl chitosan for efficient ulcerative colitis therapy.

An oral galactosylated carboxymethyl chitosan polymeric nanomicelles (Gal-N-CMCS NPs) embedded in chitosan-alginate hydrogel (CA-Gel) was developed to load cyclosporine A (CyA) as therapeutic agents against ulcerative colitis (UC). Galactose modified CMCS with macrophage targeting characteristic and CyA via a simple ultrasonication method to form Gal-N-CMCS/CyA NPs, and mixed CA-Gel to acquire the final formulation (Gal-N-CMCS/CyA Gel). The generated Gal-N-CMCS/CyA NPs displayed a desirable particle size (206.8 nm), negative surface charge (-19.5 mV), and high encapsulating efficiency (89.6 %). The morphology and release profiles were also charactered by transmission electron microscope [1] and dialysis method, respectively. Strikingly, the mucus penetration of Gal-N-CMCS/CyA NPs exceeded 90 % within 90 min. The Gal-N-CMCS NPs internalized by macrophages were 3.3-fold higher than CMCS-N NPs, thereby, enhancing the anti-inflammatory activities of NPs. Meanwhile, these NPs exhibited excellent biocompatibility, reduced the toxic effect of CyA, and targeting ability on inflammatory macrophages both in vitro and in vivo. Most importantly, in vivo studies revealed that CyA NPs could efficiently target the inflamed colon, remarkably alleviate inflammation, repair mucosal and reconstructed colonic epithelial barriers in UC mice induced by dextran sulfate sodium (DSS) via Toll-like receptor 4 -Nuclear factor kappa-B (TLR4-NF-κB) pathway. Our findings suggest that these high-performance and facilely fabricated Gal-N-CMCS/CyA NPs could be developed as a promising drug carrier for oral UC treatment.

Engineering High Strength and Super-Toughness of Unfolded Structural Proteins and their Extraordinary Anti-Adhesion Performance for Abdominal Hernia Repair.

The utility of unfolded structural proteins with diverse sequences offers multiple potentials to create functional biomaterials. However, it is challenging to overcome their structural defects for the development of biological fibers with a combination of high strength and high toughness. Herein, robust fibers from a recombinant unfolded protein consisting of resilin and supercharged polypeptide are fabricated via wet-spinning approaches. Particularly, the highly ordered structures induced by supramolecular complexation significantly improve the fiber's mechanical performance. In contrast to chemical fibers with high strength and low toughness (or vice versa), the present fibers demonstrate exceptional high strength and super-toughness, showing a breaking strength of ≈550 MPa and a toughness of ≈250 MJ m-3 , respectively, surpassing many polymers and artificial protein fibers. Remarkably, the outstanding biocompatibility and superior mechanical properties allow application of the constructed fiber patches for efficient abdominal hernia repair in rat models. In stark contrast to clinical patches, there is no observed tissue adhesion by this treatment. Therefore, this work provides a new type of engineered protein material for surgical applications.