MiRNA 24-3p-rich exosomes functionalized DEGMA-modified hyaluronic acid hydrogels for corneal epithelial healing

The damage of corneal epithelium may lead to the formation of irreversible corneal opacities and even blindness.The migration rate of corneal epithelial cells directly affects corneal repair.Here,we explored ocu-microRNA 24-3p(miRNA 24-3p)that can promote rabbit corneal epithelial cells migration and cornea repair.Exosomes,an excellent transport carrier,were exacted from adipose derived mesenchymal stem cells for loading with miRNA 24-3p to prepare miRNA 24-3p-rich exosomes(Exos-miRNA 24-3p).It can accelerate corneal epithelial migration in vitro and in vivo.For application in cornea alkali burns,we further modified hyaluronic acid with di(ethylene glycol)monomethyl ether methacrylate(DEGMA)to obtain a thermosensitive hydrogel,also reported a thermosensitive DEGMA-modified hyaluronic acid hydrogel(THH)for the controlled release of Exos-miRNA 24-3p.It formed a highly uniform and clear thin layer on the ocular surface to resist clearance from blinking and extended the drug-ocular-epithelium contact time.The use of THH-3/Exos-miRNA 24-3p for 28 days after alkali burn injury accelerated corneal epithelial defect healing and epithelial maturation.It also reduced corneal stromal fibrosis and macrophage activation.MiRNA 24-3p-rich exosomes functionalized DEGMA-modified hyaluronic acid hydrogel as a multilevel delivery strategy has a potential use for cell-free therapy of corneal epithelial regeneration.

Nanostructural origins of irreversible deformation in bone revealed by an in situ atomic force microscopy study

The structural origins of bone toughness at the nanoscale are not completely understood.Therefore,we performed in situ scanning using atomic force microscopy during macroscopic mechanical testing of antler and bovine bone,to reveal the origins of the irreversible plastic deformation at the mineralized collagen fibril(MCF)array and MCF levels.We found that the plastic deformation behavior at the nanoscale level could be divided into two stages.The first stage of plastic deformation at the nanoscale level was characterized by slippage between the MCF arrays,which contained mineral aggregate grains with regular shapes under load.In the second stage of nanoscale plastic deformation,the MCFs broke through the bonds of the extrafibrillar mineral aggregate grains and exhibited interfibrillar slippage.These nanoscale plastic deformation behaviors may thus be the origins of stress whitening and irreversible plastic deformation.Thus,the findings in this study not only shed light on the plastic deformation mechanisms of MCF arrays and MCFs,but also provide structural and mechanistic insights into bioinspired materials design and mechanisms of relevant bone diseases.