Injectable hydrogels can fill irregular defects and promote in situ tissue regrowth and regeneration. The ability of directing stem cell differentiation in a three-dimensional microenvironment for bone regeneration remains a challenge. In this study, we successfully nanoengineer an interconnected microporous networked photocrosslinkable chitosan in situ-forming hydrogel by introducing two-dimensional nanoclay particles with intercalation chemistry. The presence of the nanosilicates increases the Young’s modulus and stalls the degradation rate of the resulting hydrogels. We demonstrate that the reinforced hydrogels promote the proliferation as well as the attachment and induced the differentiation of encapsulated mesenchymal stem cells in vitro. Furthermore, we explore the effects of nanoengineered hydrogels in vivo with the critical-sized mouse calvarial defect model. Our results confirm that chitosan-montmorillonite hydrogels are able to recruit native cells and promote calvarial healing without delivery of additional therapeutic agents or stem cells, indicating their tissue engineering potential.

Exosomes are small membrane‐bound vesicles released into extracellular spaces by many types of cells. These nanovesicles carry proteins, mRNA, and miRNA, and are involved in cell waste management and intercellular communication. In the present study, it is shown that exosome release, which leads to net loss of cellular membrane and protein content, is negatively regulated by mechanistic target of rapamycin complex 1 (mTORC1). It is found that in cells and animal models exosome release is inhibited by sustained activation of mTORC1, leading to intracellular accumulation of CD63‐positive exosome precursors. Inhibition of mTORC1 by rapamycin or nutrient and growth factor deprivation stimulates exosome release, which occurs concomitantly with autophagy. The drug‐stimulated release is blocked by siRNA‐mediated downregulation of small GTPase Rab27A. Analysis of the cargo content in exosomes released from rapamycin‐treated cells reveals that inhibition of mTORC1 does not significantly alter its majority protein and miRNA profiles. These observations demonstrate that exosome release, like autophagy, is negatively regulated by mTORC1 in response to changes in nutrient and growth factor conditions.

Clinical evidence has established that concomitant traumatic brain injury (TBI) accelerates bone healing, but the underlying mechanism is unclear. This study shows that after TBI, injured neurons, mainly those in the hippocampus, release osteogenic microRNA (miRNA)-enriched small extracellular vesicles (sEVs), which targeted osteoprogenitors in bone to stimulate bone formation. We show that miR-328a-3p and miR-150-5p, enriched in the sEVs after TBI, promote osteogenesis by directly targeting the 3′UTR of FOXO4 or CBL, respectively, and hydrogel carrying miR-328a-3p-containing sEVs efficiently repaires bone defects in rats. Importantly, increased fibronectin expression on sEVs surface contributes to targeting of osteoprogenitors in bone by TBI sEVs, thereby implying that modification of the sEVs surface fibronectin could be used in bone-targeted drug delivery. Together, our work unveils a role of central regulation in bone formation and a clear link between injured neurons and osteogenitors, both in animals and clinical settings.

This study proposes a novel and facile method to synthesize high-quality NH₂-functionalized and carboxyl-functionalized graphene oxide (PPD–CFGO)/polyimide (PI) composite films with high dielectric constant (ε), low dielectric loss, high-temperature resistance and outstanding mechanical properties by in situ polymerization. In addition to the partial carboxyl groups located at the edges, the ample hydroxyl and epoxy groups bonded on the basal plane of graphene sheets were exploited to covalently bond to the amines. GO was modified by oxalic acid to obtain carboxyl-functionalized GO (CFGO) before amidation. NH₂-functionalized CFGO (PPD–CFGO), dispersing well in dimethylacetamide (DMAc), was the initial platform for polymer grafting to improve the CFGO dispersion in the polymer matrix. Partially reduced graphene nanosheets are formed during the imidization process. The PPD–CFGO/PI composite films exhibit high tensile strength (up to 848 MPa) and Young's modulus (18.5 GPa). The thermogravimetric analysis results indicate that the PPD–CFGO/PI composites have good thermal stability below 500 °C. The dielectric constant increases up to 36.9 with an increasing amount of PPD–CFGO, higher than that of the pure PI polymer by a factor of 12.5, while the dielectric loss is only 0.0075 and the breakdown strength still remains at a high level (132.5 ± 9.3 MV m⁻¹).