Rotator cuff(RC)attaches to humerus across a triphasic yet continuous tissue zones(bone-fibrocartilage-tendon),termed“enthesis”.Regrettably,rapid and functional enthesis regeneration is challenging after RC tear.The...Rotator cuff(RC)attaches to humerus across a triphasic yet continuous tissue zones(bone-fibrocartilage-tendon),termed“enthesis”.Regrettably,rapid and functional enthesis regeneration is challenging after RC tear.The existing grafts bioengineered for RC repair are insufficient,as they were engineered by a scaffold that did not mimic normal enthesis in morphology,composition,and tensile property,meanwhile cannot simultaneously stimulate the formation of bone-fibrocartilage-tendon tissues.Herein,an optimized decellularization approach based on a vacuum aspiration device(VAD)was developed to fabricate a book-shaped decellularized enthesis matrix(O-BDEM).Then,three recombinant growth factors(CBP-GFs)capable of binding collagen were synthesized by fusing a collagen-binding peptide(CBP)into the N-terminal of BMP-2,TGF-β3,or GDF-7,and zone-specifically tethered to the collagen of O-BDEM to fabricate a novel scaffold(CBP-GFs/O-BDEM)satisfying the above-mentioned requirements.After ensuring the low immunogenicity of CBP-GFs/O-BDEM by a novel single-cell mass cytometry in a mouse model,we interleaved urine-derived stem cell-sheets into this CBP-GFs/O-BDEM to bioengineer an enthesis-like graft.Its high-performance on regenerating enthesis was determined in a canine model.These findings indicate this CBP-GFs/O-BDEM may be an excellent scaffold for constructing enthesis-like graft to patch large/massive RC tears,and provide breakthroughs in fabricating graded interfacial tissue.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81902192 and 81730068)the Science and Technology Major Project of Changsha(No.kh2003015)+1 种基金the Postdoctoral Science Foundation of China(No.2019M652809)Additionally,we thank the staffs at BL01B station of National Facility for Protein Science Shanghai and the BL15U1 station of the Shanghai Synchrotron Radiation Facility,Shanghai,China,for their kind assistance during the experiments.
文摘Rotator cuff(RC)attaches to humerus across a triphasic yet continuous tissue zones(bone-fibrocartilage-tendon),termed“enthesis”.Regrettably,rapid and functional enthesis regeneration is challenging after RC tear.The existing grafts bioengineered for RC repair are insufficient,as they were engineered by a scaffold that did not mimic normal enthesis in morphology,composition,and tensile property,meanwhile cannot simultaneously stimulate the formation of bone-fibrocartilage-tendon tissues.Herein,an optimized decellularization approach based on a vacuum aspiration device(VAD)was developed to fabricate a book-shaped decellularized enthesis matrix(O-BDEM).Then,three recombinant growth factors(CBP-GFs)capable of binding collagen were synthesized by fusing a collagen-binding peptide(CBP)into the N-terminal of BMP-2,TGF-β3,or GDF-7,and zone-specifically tethered to the collagen of O-BDEM to fabricate a novel scaffold(CBP-GFs/O-BDEM)satisfying the above-mentioned requirements.After ensuring the low immunogenicity of CBP-GFs/O-BDEM by a novel single-cell mass cytometry in a mouse model,we interleaved urine-derived stem cell-sheets into this CBP-GFs/O-BDEM to bioengineer an enthesis-like graft.Its high-performance on regenerating enthesis was determined in a canine model.These findings indicate this CBP-GFs/O-BDEM may be an excellent scaffold for constructing enthesis-like graft to patch large/massive RC tears,and provide breakthroughs in fabricating graded interfacial tissue.
