Dual-engineered cartilage-targeting extracellular vesicles derived from mesenchymal stem cells enhance osteoarthritis treatment via miR-223/NLRP3/pyroptosis axis:Toward a precision therapy

Osteoarthritis(OA)is the most common disabling joint disease with no effective disease modifying drugs.Extracellular vesicles released by several types of mesenchymal stem cells could promote cartilage repair and ameliorate OA pathology in animal models,representing a novel therapeutic strategy.In this study,we demonstrated that extracellular vesicles derived from human umbilical cord mesenchymal stem cells(hUC-EVs)could maintain chondrocyte homeostasis and alleviate OA,and further revealed a novel molecular mechanism of this therapeutic effect.miR-223,which could directly bind with the 3′UTR of NLRP3 mRNA,was found to be a key miRNA for hUC-EVs to exert beneficial effects on inflammation inhibiting and cartilage protecting.For enhancing the effect on mitigating osteoarthritis,exogenous miR-223 was loaded into hUC-EVs by electroporation,and a collagen II-targeting peptide(WYRGRL)was modified onto the surface of hUC-EVs by genetic engineering to achieve a more targeted and efficient RNA delivery to the cartilage.The dual-engineered EVs showed a maximal effect on inhibiting the NLRP3 inflammasome activation and chondrocyte pyroptosis,and offered excellent results for the treatment of OA.This study provides a novel theoretical basis and a promising therapeutic strategy for the application of engineered extracellular vesicles in OA treatment.

Chemical Modification of Silk Proteins: Current Status and Future Prospects

Silk extracted from the cocoon of silkworm has been used as textile materials for thousands of years.Recently,silk has been redefined as a protein-based biomaterial with great potential in biomedical applications owing to its excellent mechanical properties,biocompatibility,and biodegradability.With the advances in silk processing technologies,a broad range of intriguing silk-based functional biomaterials have been made and applied for various biomedical uses.However,most of these materials are based on natural silk proteins without chemical modification,leading to limited control of properties and functions(e.g.,biodegradability and bioactivity).A chemical toolbox for modifying the silk proteins is required to achieve versatile silk-based materials with precisely designed properties or functions for different applications.Furthermore,inspired by the traditional fine chemical industry based on synthetic chemistry,developing silk-based fine chemicals with special functions can significantly extend the applications of silk materials,particularly in biomedical fields.This review summarizes the recent progress on chemical modification of silk proteins,focusing on the methodologies and applications.We also discuss the challenges and opportunities of these chemically modified silk proteins.