No abstract

Microbial infection has been considered as one of the most critical challenges in bioengineering applications especially in tissue regeneration, which engenders severe threat to public health. Herein, a hydrogel performing properties of rapid self-healing, on-demand antibiosis and controlled cargo release was fabricated by a simple assembly of Fe complex as the cross-linker and hyaluronic acid as the gel network. This hydrogel is able to locally degrade and release Fe to kill bacteria as needed because of hyaluronidase excreted by surrounding bacteria, resulting in efficient antibacterial activity against different types of bacteria. The sustained release property of certain types of growth factors was also observed from this hydrogel owing to its dense network. Moreover, this hydrogel could repeatedly heal itself in minutes because of the coordination interaction between Fe and COOH, exhibiting good potential in bioengineering applications on the exposed tissue, where the materials are easily damaged during daily life. When topically applied onto damaged mouse skin with infection of Staphylococcus aureus, the hydrogel is able to inhibit microbial infections, meanwhile promoting cutaneous regeneration, which formed new skin with no inflammation within a 10 day treatment. These results demonstrate the potential application of this self-healing hydrogel for the integrated therapy of antibiosis and tissue regeneration.

Engineered extracellular vesicles (EVs) carrying therapeutic molecules are promising candidates for disease therapies. Yet, engineering EVs with optimal functions is a challenge that requires careful selection of functionally specific vesicles and a proper engineering strategy. Here, we constructed chimeric apoptotic bodies (cABs) for on-demand inflammation modulation by combining pure membrane from apoptotic bodies (ABs) as a bioconjugation/regulation module and mesoporous silica nanoparticles (MSNs) as a carrier module. MSNs were preloaded with anti-inflammatory agents (microRNA-21 or curcumin) and modified with stimuli-responsive molecules to achieve accurate cargo release at designated locations. The resulting cABs actively target macrophages in the inflammatory region and effectively promote M2 polarization of these macrophages to modulate inflammation due to the synergistic regulatory effects of AB membranes and the intracellular release of preloaded cargos. This work provides strategies to arbitrarily engineer modular EVs that integrate the advantages of natural EVs and synthetic materials for various applications.

An injectable hydrogel was developed using mesoporous silica nanoparticles to co-deliver miR222 and aspirin, osteogenesis was enhanced by stimulating innervation.