Bone/cartilage organoid on-chip:Construction strategy and application

The necessity of disease models for bone/cartilage related disorders is well-recognized,but the barrier between ex-vivo cell culture,animal models and the real human body has been pending for decades.The organoid-on-a-chip technique showed opportunity to revolutionize basic research and drug screening for diseases like osteoporosis and arthritis.The bone/cartilage organoid on-chip(BCoC)system is a novel platform of multi-tissue which faithfully emulate the essential elements,biologic functions and pathophysiological response under real circumstances.In this review,we propose the concept of BCoC platform,summarize the basic modules and current efforts to orchestrate them on a single microfluidic system.Current disease models,unsolved problems and future challenging are also discussed,the aim should be a deeper understanding of diseases,and ultimate realization of generic ex-vivo tools for further therapeutic strategies of pathological conditions.

M2 macrophage-derived exosomes promote diabetic fracture healing by acting as an immunomodulator

Diabetes mellitus is a chronically inflamed disease that predisposes to delayed fracture healing.Macrophages play a key role in the process of fracture healing by undergoing polarization into either M1 or M2 subtypes,which respectively exhibit pro-inflammatory or anti-inflammatory functions.Therefore,modulation of macrophage polarization to the M2 subtype is beneficial for fracture healing.Exosomes perform an important role in improving the osteoimmune microenvironment due to their extremely low immunogenicity and high bioactivity.In this study,we extracted the M2-exosomes and used them to intervene the bone repair in diabetic fractures.The results showed that M2-exosomes significantly modulate the osteoimmune microenvironment by decreasing the proportion of M1 macrophages,thereby accelerating diabetic fracture healing.We further confirmed that M2-exosomes induced the conversion of M1 macrophages into M2 macrophages by stimulating the PI3K/AKT pathway.Our study offers a fresh perspective and a potential therapeutic approach for M2-exosomes to improve diabetic fracture healing.

Smart Hydrogels for Bone Reconstruction via Modulating the Microenvironment

Rapid and effective repair of injured or diseased bone defects remains a major challenge due to shortages of implants.Smart hydrogels that respond to internal and external stimuli to achieve therapeutic actions in a spatially and temporally controlled manner have recently attracted much attention for bone therapy and regeneration.These hydrogels can be modified by introducing responsive moieties or embedding nanoparticles to increase their capacity for bone repair.Under specific stimuli,smart hydrogels can achieve variable,programmable,and controllable changes on demand to modulate the microenvironment for promoting bone healing.In this review,we highlight the advantages of smart hydrogels and summarize their materials,gelation methods,and properties.Then,we overview the recent advances in developing hydrogels that respond to biochemical signals,electromagnetic energy,and physical stimuli,including single,dual,and multiple types of stimuli,to enable physiological and pathological bone repair by modulating the microenvironment.Then,we discuss the current challenges and future perspectives regarding the clinical translation of smart hydrogels.