title: In vitro investigation of a tissue-engineered cell-tendon complex mimicking the transitional architecture at the ligament-bone interface.
abstract: Restoration of the transitional ligament-bone interface is critical for graft-bone integration. We postulated that an allogenic scaffold mimicking the fibrogenic, chondrogenic, and osteogenic transition gradients could physiologically promote ligament-bone incorporation. The aim of this study was to construct and characterize a composite tendon scaffold with a continuous and heterogeneous transition region mimicking a native ligament insertion site. Genetically modified heterogeneous cell populations were seeded within specific regions of decellularized rabbit Achilles tendons to fabricate a stratified scaffold containing three biofunctional regions supporting fibrogenesis, chondrogenesis, and osteogenesis. The observed morphology, architecture, cytocompatibility, and biomechanics of the scaffolds demonstrated their improved bio-physico-chemical properties. The formation of the transitional regions was augmented via enhanced delivery of two transcription factors, sex determining region Y-box 9 and runt-related transcription factor 2, which also triggered early up-regulated expression of cartilage- and bone-relevant markers, according to quantitative PCR and immunoblot analyses. Gradient tissue-specific matrix formation was also confirmed within the predesignated regions via histological staining and immunofluorescence assays. These results suggest that a transitional interface could be replicated on an engineered tendon through stratified tissue integration. The scaffold offers the advantages of a multitissue transition involving controlled cellular interactions and matrix heterogeneity, which can be applied for the regeneration of the ligament-bone interface.
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Xinqiao Street, Chongqing, PR China.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Xinqiao Street, Chongqing, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Changjiang Street, Chongqing, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: National & Regional United Engineering Laboratory of Tissue Engineering, Department of Biomedical Materials Science, Third Military Medical University, Gaotanyan Street, Chongqing, PR China.
authors.forename: Shiwu
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Xinqiao Street, Chongqing, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Xinqiao Street, Chongqing, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Xinqiao Street, Chongqing, PR China dpapofman@gmail.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000125:Achilles Tendon / Q000637:transplantation; D000818:Animals; D001696:Biomechanical Phenomena; D001842:Bone and Bones / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D002460:Cell Line; D020219:Chondrogenesis / Q000235:genetics / Q000502:physiology; D015870:Gene Expression; D066298:In Vitro Techniques; D008022:Ligaments / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008855:Microscopy, Electron, Scanning; D016348:Osseointegration; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology; D040081:Protein Array Analysis; D011817:Rabbits; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
keywords: Ligament-bone interface; chondrogenesis; decellularized tendon; osteogenesis; transition