Black phosphorus-based 2D materials for bone therapy

Since their discovery,Black Phosphorus(BP)-based nanomaterials have received extensive attentions in the fields of electromechanics,optics and biomedicine,due to their remarkable properties and excellent biocompatibility.The most essential feature of BP is that it is composed of a single phosphorus element,which has a high degree of homology with the inorganic components of natural bone,therefore it has a full advantage in the treatment of bone defects.This review will first introduce the source,physicochemical properties,and degradation products of BP,then introduce the remodeling process of bone,and comprehensively summarize the progress of BP-based materials for bone therapy in the form of hydrogels,polymer membranes,microspheres,and three-dimensional(3D)printed scaffolds.Finally,we discuss the challenges and prospects of BP-based implant materials in bone immune regulation and outlook the future clinical application.

Capturing dynamic biological signals via bio-mimicking hydrogel for precise remodeling of soft tissue

Soft tissue remodeling is a sophisticated process that sequentially provides dynamic biological signals to guide cell behavior.However,capturing these signals within hydrogel and directing over time has still been unrealized owing to the poor comprehension of physiological processes.Here,a bio-mimicking hydrogel is designed via thiol-ene click reaction to capture the early physical signal triggered by inflammation,and the chemical signals provided with chemokine and natural adhesion sites,which guaranteed the precise soft tissue remodeling.This bio-mimicking hydrogel efficiently facilitated cell anchoring,migration,and invasion in the 3D matrix due to the permissive space and the interaction with integrin receptors.Besides,the covalently grafted chemokine-like peptide is optimal for colonization and functional differentiation of endothelial cells through a HIF-1αdependent signal pathway.Furthermore,the early polarization of macrophages,collagen deposition and angiogenesis in rat acute wound model,and the increased blood perfusion in mouse skin flap model have confirmed that the bio-mimicking hydrogel realized precise soft tissue remodeling and opens new avenues for the phased repair of different tissues such as nerve,myocardium,and even bone.

Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries

Central nervous system(CNS)injuries,including stroke,traumatic brain injury,and spinal cord injury,are essential causes of death and long-term disability and are difficult to cure,mainly due to the limited neuron regeneration and the glial scar formation.Herein,we apply extracellular vesicles(EVs)secreted by M2 microglia to improve the differentiation of neural stem cells(NSCs)at the injured site,and simultaneously modify them with the injured vascular targeting peptide(DA7R)and the stem cell recruiting factor(SDF-1)on their surface via copper-free click chemistry to recruit NSCs,inducing their neuronal differentiation,and serving as the nanocarriers at the injured site(Dual-EV).Results prove that the Dual-EV could target human umbilical vascular endothelial cells(HUVECs),recruit NSCs,and promote the neuronal differentiation of NSCs in vitro.Furthermore,10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis,and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs,miR30b-3p,miR-222-3p,miR-129-5p,and miR-155-5p may exert effect of inducing NSC to differentiate into neurons.In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice,potentiate NSCs recruitment,and increase neurogenesis.This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells,and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Engineered extracellular vesicles for ischemic stroke treatment

Dear Editor,Nanotechnology-based therapeutic strategies have been proven effective in diseases including cancer,infection,inflammation,etc.1 However,the application of nanotechnology is greatly restricted in the treatment of central nervous system(CNS)disorders due to physiological CNS barriers.For example,the blood-brain barrier(BBB)can be the“Maginot line”for pharmacologically active molecules,blocking them out of the CNS.