The escalating prevalence of anterior cruciate ligament(ACL)injuries in sports necessitates innovative strategies for ACL reconstruction.In this study,we propose a multiphasic bone-ligament-bone(BLB)integrated scaffol...The escalating prevalence of anterior cruciate ligament(ACL)injuries in sports necessitates innovative strategies for ACL reconstruction.In this study,we propose a multiphasic bone-ligament-bone(BLB)integrated scaffold as a potential solution.The BLB scaffold comprised two polylactic acid(PLA)/deferoxamine(DFO)@mesoporous hydroxyapatite(MHA)thermally induced phase separation(TIPS)scaffolds bridged by silk fibroin(SF)/connective tissue growth factor(CTGF)@Poly(L-lactide-co-ε-caprolactone)(PLCL)nanofiber yarn braided scaffold.This combination mimics the native architecture of the ACL tissue.The mechanical properties of the BLB scaffolds were determined to be compatible with the human ACL.In vitro experiments demonstrated that CTGF induced the expression of ligament-related genes,while TIPS scaffolds loaded with MHA and DFO enhanced the osteogenic-related gene expression of bone marrow stem cells(BMSCs)and promoted the migration and tubular formation of human umbilical vein endothelial cells(HUVECs).In rabbit models,the BLB scaffold efficiently facilitated ligamentization and graft-bone integration processes by providing bioactive substances.The double delivery of DFO and calcium ions by the BLB scaffold synergistically promoted bone regeneration,while CTGF improved collagen formation and ligament healing.Collectively,the findings indicate that the BLB scaffold exhibits substantial promise for ACL reconstruction.Additional investigation and advancement of this scaffold may yield enhanced results in the management of ACL injuries.展开更多
基金supported by the Fundamental Research Funds for the Central Universities(2232019A3-07,2232019D3-20)the Science and Technology Commission of Shanghai Municipality(20S31900900,20DZ2254900)+8 种基金the Sino German Science Foundation Research Exchange Center(M0263)the National Natural Science Foundation of China(82102579,81871753)the Shanghai Rising-Star Program(22QC1401200)the Basic Scientific Research Project of Shanghai Sixth People’s Hospital(ynqn202101)the Opening Project of National Engineering Laboratory for Modern Silk,Soochow University(SDGC2149)the National Key Research and Development Program of China(2018YFC1106200,2018YFC1106202)the Key R&D Program of Shandong province(2019JZZY011104)the Deutsche Forschungsgemeinschaft(German Research Foundation(B.R.:RO 2511/11-1),This project was also supported by Researchers Supporting Project Number(RSP2023R65)King Saud University,Riyadh,Saudi Arabia,and the combined Sino-German Mobility Programme of the National Natural Science Foundation of China(NSFC)/Deutsche Forschungsgemeinschaft(German Research Foundation(B.R.:M0332).
文摘The escalating prevalence of anterior cruciate ligament(ACL)injuries in sports necessitates innovative strategies for ACL reconstruction.In this study,we propose a multiphasic bone-ligament-bone(BLB)integrated scaffold as a potential solution.The BLB scaffold comprised two polylactic acid(PLA)/deferoxamine(DFO)@mesoporous hydroxyapatite(MHA)thermally induced phase separation(TIPS)scaffolds bridged by silk fibroin(SF)/connective tissue growth factor(CTGF)@Poly(L-lactide-co-ε-caprolactone)(PLCL)nanofiber yarn braided scaffold.This combination mimics the native architecture of the ACL tissue.The mechanical properties of the BLB scaffolds were determined to be compatible with the human ACL.In vitro experiments demonstrated that CTGF induced the expression of ligament-related genes,while TIPS scaffolds loaded with MHA and DFO enhanced the osteogenic-related gene expression of bone marrow stem cells(BMSCs)and promoted the migration and tubular formation of human umbilical vein endothelial cells(HUVECs).In rabbit models,the BLB scaffold efficiently facilitated ligamentization and graft-bone integration processes by providing bioactive substances.The double delivery of DFO and calcium ions by the BLB scaffold synergistically promoted bone regeneration,while CTGF improved collagen formation and ligament healing.Collectively,the findings indicate that the BLB scaffold exhibits substantial promise for ACL reconstruction.Additional investigation and advancement of this scaffold may yield enhanced results in the management of ACL injuries.
