3D-printed cell-free PCL-MECM scaffold with biomimetic micro-structure and micro-environment to enhance in situ meniscus regeneration

Despite intensive effort was made to regenerate injured meniscus by cell-free strategies through recruiting endogenous stem/progenitor cells,meniscus regeneration remains a great challenge in clinic.In this study,we found decellularized meniscal extracellular matrix(MECM)preserved native meniscal collagen and glycosaminoglycans which could be a good endogenous regeneration guider for stem cells.Moreover,MECM significantly promoted meniscal fibrochondrocytes viability and proliferation,increased the expression of type II collagen and proteoglycans in vitro.Meanwhile,we designed 3D-printed polycaprolactone(PCL)scaffolds which mimic the circumferential and radial collagen orientation in native meniscus.Taken these two advantages together,a micro-structure and micro-environment dually biomimetic cell-free scaffold was manipulated.This cell-free PCL-MECM scaffold displayed superior biocompatibility and yielded favorable biomechanical capacities closely to native meniscus.Strikingly,neo-menisci were regenerated within PCL-MECM scaffolds which were transplanted into knee joints underwent medial meniscectomy in rabbits and sheep models.Histological staining confirmed neo-menisci showed meniscus-like heterogeneous staining.Mankin scores showed PCL-MECM scaffold could protect articular cartilage well,and knee X-ray examination revealed same results.Knee magnetic resonance imaging(MRI)scanning also showed some neo-menisci in PCL-MECM scaffold group.In conclusion,PCL-MECM scaffold appears to optimize meniscus regeneration.This could represent a promising approach worthy of further investigation in preclinical applications.