Sequential intervention of anti-inflammatory and osteogenesis with silk fibroin coated polyethylene terephthalate artificial ligaments for anterior cruciate ligament reconstruction.

Graft-host integration after the anterior cruciate ligament (ACL) reconstruction sequentially follows the prognosis from the inflammation period to the regeneration period. However, due to insufficient bioactivity, polyethylene terephthalate (PET) artificial ligaments often require a long period for graft-host integration. To improve graft-host integration, sequential therapy targeting multifactor is widely advocated. In this study, a multilayer regenerated silk fibroin (RSF) coating loaded with heparin and bone morphogenetic protein binding peptide (BBP) for differentiated release was introduced on the surface of the PET artificial ligament by a stepwise deposition method. The drug release profiles of heparin and BBP on the coated PET artificial ligament indicated the features of differential drug release, i.e. , with heparin in the outermost layer releasing a significant amount (more than 60%) during the first 5 days while BBP in the inner layer only releasing a small amount ( ca. 30%) within 1 week without burst release. Based on the isometric ACL reconstruction model of rabbits, such drug-loaded RSF coating was verified to be able to modulate the early inflammatory response and promote the maturation of the graft in the articular cavity, meanwhile, it provided a continuous and stable signal of osteogenic induction to improve graft-bone integration. Thus, sequential intervention with heparin and BBP proved to be a reliable combination, and multifunctional RSF-coated PET artificial ligaments hold great potential for improving the clinical efficacy of ACL reconstruction.