A bioactive injectable self-healing anti-inflammatory hydrogel with ultralong extracellular vesicles release synergistically enhances motor functional recovery of spinal cord injury

The repair and motor functional recovery after spinal cord injury(SCI)remains a worldwide challenge.The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI.Using mesenchymal stem cells(MSCs)derived extracellular vesicles to replace MSCs transplantation and mimic cell paracrine secretions provides a potential strategy for microenvironment regulation.However,the effective preservation and controlled release of extracellular vesicles in the injured spinal cord tissue are still not satisfied.Herein,we fabricated an injectable adhesive anti-inflammatory F127-polycitrate-polyethyleneimine hydrogel(FE)with sustainable and long term extracellular vesicle release(FE@EVs)for improving motor functional recovery after SCI.The orthotopic injection of FE@EVs hydrogel could encapsulate extracellular vesicles on the injured spinal cord,thereby synergistically induce efficient integrated regulation through suppressing fibrotic scar formation,reducing inflammatory reaction,promoting remyelination and axonal regeneration.This study showed that combining extracellular vesicles into bioactive multifunctional hydrogel should have great potential in achieving satisfactory locomotor recovery of central nervous system diseases.

CO_2-sensitive Amphiphilic Triblock Copolymer Self-assembly Morphology Transition and Accelerating Drug Release from Polymeric Vesicle

A series of triblock copolymers, containing a CO_2-switchable block poly（2-（dimethylamino）ethyl methacrylate）（PDM） block and two symmetrical hydrophilic blocks polyacrylamide（PAM）, were synthesized using atom transfer radical polymerization（ATRP） method. The p H and conductivity tests showed that the triblock copolymer exhibited switchable responsiveness to CO_2, i.e. a relatively low conductivity of solution could be switched on and off by bubbling and removing of CO_2, and the triblock copolymer aqueous solution displayed a CO_2-switchable viscosity variation. The changes were all attributed to protonation of tertiary amine groups in PDM blocks and proven by 1 H-NMR. Cryogenic transmission electron microscopy and dynamic light scattering characterization demonstrated that the viscosity variation was the result of a unilamellar vesicle-network aggregate structure transition. The release of rhodamine B from the vesicles with and without CO_2 stimuli showed the potential application in drug delivery domains; after CO_2 bubbling, the drug release rate could be accelerated. Finally, reasonable mechanism of CO_2-switchable morphology changes and CO_2-induced drug release was proposed.

Enhancement of gemcitabine against pancreatic cancer by loading in mesoporous silica vesicles

Gemcitabine（Gem） is currently the first-line chemotherapeutic drug in management of pancreatic cancer, however the therapeutic efficacy of Gem is limited due to its short half-life and poor cell membrane permeability. Here we designed mesoporous silica vesicles（MSVs） with large pore sizes as a novel drug delivery system. The MSVs were synthesized using cetyltrimethyl ammonium bromide（CTAB） as a structure-directing agent, tetraethoxysilane（TEOS） as silica source in n-hexane/water biliquid system. By virtue of the large pore size and large pore volume of the MSVs, Gem was loaded into the mesoporous of MSVs via ＂nanocasting＂ method. In vitro drug release experiments of gemcitabineloaded MSVs showed an accelerating release of gemcitabine in acidic condition. These fluorescently labeled MSVs could be effectively internalized by both a human（BxPC-3） and a mouse pancreatic cancer cell lines（Pan02）. Additionally, some MSVs could even reach the nuclei of the pancreatic cancer cells. Cell viability assays demonstrated that gemcitabine-loaded MSVs exhibited enhanced anticancer activity in inhibiting the proliferation of Bx PC-3 and Pan02 cells compared with free Gem, while the MSVs alone showed no significant cytotoxicity. Our results indicate that our synthesized MSVs might represent a promising novel drug delivery platform for the treatment of pancreatic cancer.