The rotator cuff is prone to tear under degenerative changes or mechanical injury,leading to excessive inflammation,extracellular matrix degradation,and unsatisfactory prognosis.Interleukin-4(IL-4)was used to induce m...The rotator cuff is prone to tear under degenerative changes or mechanical injury,leading to excessive inflammation,extracellular matrix degradation,and unsatisfactory prognosis.Interleukin-4(IL-4)was used to induce macrophages polarization toward M2 phenotype.By mapping IL 4-activated pathways and applying peptidome profiling,macrophage-derived peptide 1(MDP1)was identified and shown to promote the phos-phorylation of STAT3 and STAT6,thereby inducing the polarization of M0 macrophages toward the anti-inflammatory M2 phenotype.A functionally graded scaffold woven from electrospun nanofiber yarns was developed,with MDP1 and hydroxyapatite(HA)loaded onto its corresponding interfaces.During rotator cuff repair process,the scaffold functioned as an augmentation patch,with mechanical properties(Young’s modulus,ca.280 MPa)comparable to native tendons,prevented rotator cuff re-tearing in an early stage.MDP1 was incorporated into scaffolds to modulate an excessive inflammatory response,while HA was used to enhance bio-mineralization for enhanced osteointegration.Through a multidimensional collaborative repair strategy,this functionally graded scaffold not only mimicked the tendon-bone interface,but also significantly suppressed local inflammation at the interface,as evidenced by a 60.6%and 66.5%reduction in IL-6-positive areas at 2 and 4 months,respectively,compared with the control group.Furthermore,it promoted tissue regeneration in the damaged region,resulting in a 32.6%increase in Young’s modulus,thereby ultimately enhancing rotator cuff performance.The multifunctionally graded scaffold may offer an invaluable solution to promote rotator cuff tear healing and potentially other related disciplines.展开更多
基金supported by the Medical-Engineering Interdisci-plinary Collaborative Project(Grants No.2023DHYGJC-YBB04)be-tween Shanghai Tongren Hospital and Donghua UniversityFundamental Research Funds for the Central Universities(project number YG2024QNA62)+6 种基金the Program of Shanghai Municipal Commis-sion of Health(Grants No.20224Y0092)the Laboratory Open Fund of Key Technology and Materials in Minimally Invasive Spine Surgery(Grants No.2024JZWC-YBB06)supported by Sci-ence and Technology Commission of Shanghai Municipality,China(20DZ2254900)Sino German Science Foundation Research Exchange Center,China(M-0263)China Education Association for Interna-tional Exchange(2022181)supported by Ongoing Research Funding program,(ORF-2025-65)King Saud Uni-versity,Riyadh,Saudi Arabia.
文摘The rotator cuff is prone to tear under degenerative changes or mechanical injury,leading to excessive inflammation,extracellular matrix degradation,and unsatisfactory prognosis.Interleukin-4(IL-4)was used to induce macrophages polarization toward M2 phenotype.By mapping IL 4-activated pathways and applying peptidome profiling,macrophage-derived peptide 1(MDP1)was identified and shown to promote the phos-phorylation of STAT3 and STAT6,thereby inducing the polarization of M0 macrophages toward the anti-inflammatory M2 phenotype.A functionally graded scaffold woven from electrospun nanofiber yarns was developed,with MDP1 and hydroxyapatite(HA)loaded onto its corresponding interfaces.During rotator cuff repair process,the scaffold functioned as an augmentation patch,with mechanical properties(Young’s modulus,ca.280 MPa)comparable to native tendons,prevented rotator cuff re-tearing in an early stage.MDP1 was incorporated into scaffolds to modulate an excessive inflammatory response,while HA was used to enhance bio-mineralization for enhanced osteointegration.Through a multidimensional collaborative repair strategy,this functionally graded scaffold not only mimicked the tendon-bone interface,but also significantly suppressed local inflammation at the interface,as evidenced by a 60.6%and 66.5%reduction in IL-6-positive areas at 2 and 4 months,respectively,compared with the control group.Furthermore,it promoted tissue regeneration in the damaged region,resulting in a 32.6%increase in Young’s modulus,thereby ultimately enhancing rotator cuff performance.The multifunctionally graded scaffold may offer an invaluable solution to promote rotator cuff tear healing and potentially other related disciplines.
