Engineering an enthesis-like graft for rotator cuff repair: An approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducers

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 e...

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Main Authors: Can Chen, Qiang Shi, Muzhi Li, Yang Chen, Tao Zhang, Yan Xu, Yunjie Liao, Shulin Ding, Zhanwen Wang, Xing Li, Chunfeng Zhao, Lunquan Sun, Jianzhong Hu, Hongbin Lu
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2022-10-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X21005958
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author Can Chen
Qiang Shi
Muzhi Li
Yang Chen
Tao Zhang
Yan Xu
Yunjie Liao
Shulin Ding
Zhanwen Wang
Xing Li
Chunfeng Zhao
Lunquan Sun
Jianzhong Hu
Hongbin Lu
author_facet Can Chen
Qiang Shi
Muzhi Li
Yang Chen
Tao Zhang
Yan Xu
Yunjie Liao
Shulin Ding
Zhanwen Wang
Xing Li
Chunfeng Zhao
Lunquan Sun
Jianzhong Hu
Hongbin Lu
author_sort Can Chen
collection DOAJ
description 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.
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spelling doaj.art-62ce21acf4a24395ba3f71a71528391e2024-04-17T00:44:12ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2022-10-0116451471Engineering an enthesis-like graft for rotator cuff repair: An approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducersCan Chen0Qiang Shi1Muzhi Li2Yang Chen3Tao Zhang4Yan Xu5Yunjie Liao6Shulin Ding7Zhanwen Wang8Xing Li9Chunfeng Zhao10Lunquan Sun11Jianzhong Hu12Hongbin Lu13Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Rehabilitation, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, ChinaDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, 410013, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, ChinaDivision of Orthopedic Research and Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, 55905, United StatesCenter for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, 410008, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Corresponding author. Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, 410008, Hunan, China.Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Corresponding author. Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, 410008, Hunan, China.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.http://www.sciencedirect.com/science/article/pii/S2452199X21005958Acellular matrixCollagen-binding peptideStem cell differentiation inducerEnthesis regenerationRotator cuff
spellingShingle Can Chen
Qiang Shi
Muzhi Li
Yang Chen
Tao Zhang
Yan Xu
Yunjie Liao
Shulin Ding
Zhanwen Wang
Xing Li
Chunfeng Zhao
Lunquan Sun
Jianzhong Hu
Hongbin Lu
Engineering an enthesis-like graft for rotator cuff repair: An approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducers
Bioactive Materials
Acellular matrix
Collagen-binding peptide
Stem cell differentiation inducer
Enthesis regeneration
Rotator cuff
title Engineering an enthesis-like graft for rotator cuff repair: An approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducers
title_full Engineering an enthesis-like graft for rotator cuff repair: An approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducers
title_fullStr Engineering an enthesis-like graft for rotator cuff repair: An approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducers
title_full_unstemmed Engineering an enthesis-like graft for rotator cuff repair: An approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducers
title_short Engineering an enthesis-like graft for rotator cuff repair: An approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducers
title_sort engineering an enthesis like graft for rotator cuff repair an approach to fabricate highly biomimetic scaffold capable of zone specifically releasing stem cell differentiation inducers
topic Acellular matrix
Collagen-binding peptide
Stem cell differentiation inducer
Enthesis regeneration
Rotator cuff
url http://www.sciencedirect.com/science/article/pii/S2452199X21005958
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