Adhesion after tendon injury,which can result in limb movement disorders,is a common clinical complication;however,effective treatment methods are lacking.Hyaluronic acid hydrogels are a new biomedical material used t...Adhesion after tendon injury,which can result in limb movement disorders,is a common clinical complication;however,effective treatment methods are lacking.Hyaluronic acid hydrogels are a new biomedical material used to prevent tendon adhesion owing to their good biocompatibility.In addition,potential drugs that inhibit adhesion formation have gradually been discovered.The anti-adhesion effects of a combination of loaded drugs into hydrogels have become an emerging trend.However,current drug delivery systems usually lack specific regulation of drug release,and the effectiveness of drugs for treating tendon adhesions is mostly flawed.In this study,we identified a new drug,imatinib mesylate(IM),that prevents tendon adhesion and explored its related molecular pathways.In addition,we designed a pH-responsive sustained-release hydrogel for delivery.Using the metal-organic framework ZIF-8 as a drug carrier,we achieved controlled drug release to increase the effective drug dose at the peak of adhesion formation to achieve better therapeutic effects.The results showed that IM blocked the formation of peritendon adhesions by inhibiting the PDGFRβ/ERK/STAT3/CLDN1 pathway.Furthermore,the hydrogel with ZIF-8 exhibited better physical properties and drug release curves than the hydrogel loaded only with drugs,showing better prevention and treatment effects on tendon adhesion.展开更多
基金supported by the National Natural Science Foundation of China(No.81902234,82172408 and 81772314)Principle Investigator Innovation Team of Both Shanghai Sixth People’s Hospital and Shanghai Institute of Nutrition and Health,Shanghai Jiao Tong University Medical College“Two-hundred Talent”Program(No.20191829)+3 种基金The Second Three-Year Action Plan for Promoting Clinical Skills and Clinical Innovation in Municipal Hospitals of Shanghai Shenkang(No.SHDC2020CR4032)Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration(No.20DZ2254100)Original Exploration project(22ZR1480300)Outstanding Academic Leaders(Youth)project(21XD1422900)of Shanghai Science and Technology Innovation Action Plan.We are also grateful to Professor Jun Qin(Shanghai Institute of Nutrition and Health,Chinese Academy of Sciences)for his technical assistance.
文摘Adhesion after tendon injury,which can result in limb movement disorders,is a common clinical complication;however,effective treatment methods are lacking.Hyaluronic acid hydrogels are a new biomedical material used to prevent tendon adhesion owing to their good biocompatibility.In addition,potential drugs that inhibit adhesion formation have gradually been discovered.The anti-adhesion effects of a combination of loaded drugs into hydrogels have become an emerging trend.However,current drug delivery systems usually lack specific regulation of drug release,and the effectiveness of drugs for treating tendon adhesions is mostly flawed.In this study,we identified a new drug,imatinib mesylate(IM),that prevents tendon adhesion and explored its related molecular pathways.In addition,we designed a pH-responsive sustained-release hydrogel for delivery.Using the metal-organic framework ZIF-8 as a drug carrier,we achieved controlled drug release to increase the effective drug dose at the peak of adhesion formation to achieve better therapeutic effects.The results showed that IM blocked the formation of peritendon adhesions by inhibiting the PDGFRβ/ERK/STAT3/CLDN1 pathway.Furthermore,the hydrogel with ZIF-8 exhibited better physical properties and drug release curves than the hydrogel loaded only with drugs,showing better prevention and treatment effects on tendon adhesion.
