Osteoarthritis(OA)of the knee joint is a degenerative disease initiated by mechanical stress that affects millions of individuals.The disease manifests as joint damage and synovial inflammation.Post-traumatic osteoart...Osteoarthritis(OA)of the knee joint is a degenerative disease initiated by mechanical stress that affects millions of individuals.The disease manifests as joint damage and synovial inflammation.Post-traumatic osteoarthritis(PTOA)is a specific form of OA caused by mechanical trauma to the joint.The progression of PTOA is prevented by immediate post-injury therapeutic intervention.Intra-articular injection of anti-inflammatory therapeutics(e.g.corticosteroids)is a common treatment option for OA before end-stage surgical intervention.However,the efficacy of intra-articular injection is limited due to poor drug retention time in the joint space and the variable efficacy of corticosteroids.Here,we endeavored to characterize a four-arm maleimide-functionalized polyethylene glycol(PEG-4MAL)hydrogel system as a‘mechanical pillow’to cushion the load-bearing joint,withstand repetitive loading and improve the efficacy of intra-articular injections of nanoparticles containing dexamethasone,an anti-inflammatory agent.PEG-4MAL hydrogels maintained their mechanical properties after physiologically relevant cyclic compression and released therapeutic payload in an on-demand manner under in vitro inflammatory conditions.Importantly,the on-demand hydrogels did not release nanoparticles under repetitive mechanical loading as experienced by daily walking.Although dexamethasone had minimal protective effects on OA-like pathology in our studies,the PEG-4MAL hydrogel functioned as a mechanical pillow to protect the knee joint from cartilage degradation and inhibit osteophyte formation in an in vivo load-induced OA mouse model.展开更多
基金the National Institutes of Health[R01-AI132738-01A1 awarded to A.S.,R21-AR064034 awarded to M.C.H.v.d.M.]the National Science Foundation CAREER award[DMR-1554275 awarded to A.S.]+2 种基金3M Non-Tenured Faculty Award(awarded to A.S.),Cornell CCMR[NSF DMR-1719875]Cornell Sloan and Colman Diversity Fellowships(awarded to T.A.W.)GAANN Fellowship(awarded to D.T.H.).
文摘Osteoarthritis(OA)of the knee joint is a degenerative disease initiated by mechanical stress that affects millions of individuals.The disease manifests as joint damage and synovial inflammation.Post-traumatic osteoarthritis(PTOA)is a specific form of OA caused by mechanical trauma to the joint.The progression of PTOA is prevented by immediate post-injury therapeutic intervention.Intra-articular injection of anti-inflammatory therapeutics(e.g.corticosteroids)is a common treatment option for OA before end-stage surgical intervention.However,the efficacy of intra-articular injection is limited due to poor drug retention time in the joint space and the variable efficacy of corticosteroids.Here,we endeavored to characterize a four-arm maleimide-functionalized polyethylene glycol(PEG-4MAL)hydrogel system as a‘mechanical pillow’to cushion the load-bearing joint,withstand repetitive loading and improve the efficacy of intra-articular injections of nanoparticles containing dexamethasone,an anti-inflammatory agent.PEG-4MAL hydrogels maintained their mechanical properties after physiologically relevant cyclic compression and released therapeutic payload in an on-demand manner under in vitro inflammatory conditions.Importantly,the on-demand hydrogels did not release nanoparticles under repetitive mechanical loading as experienced by daily walking.Although dexamethasone had minimal protective effects on OA-like pathology in our studies,the PEG-4MAL hydrogel functioned as a mechanical pillow to protect the knee joint from cartilage degradation and inhibit osteophyte formation in an in vivo load-induced OA mouse model.
