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...
Main Authors: | , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1797203570292948992 |
---|---|
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. |
first_indexed | 2024-04-24T08:21:26Z |
format | Article |
id | doaj.art-62ce21acf4a24395ba3f71a71528391e |
institution | Directory Open Access Journal |
issn | 2452-199X |
language | English |
last_indexed | 2024-04-24T08:21:26Z |
publishDate | 2022-10-01 |
publisher | KeAi Communications Co., Ltd. |
record_format | Article |
series | Bioactive Materials |
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 |
work_keys_str_mv | AT canchen engineeringanenthesislikegraftforrotatorcuffrepairanapproachtofabricatehighlybiomimeticscaffoldcapableofzonespecificallyreleasingstemcelldifferentiationinducers AT qiangshi engineeringanenthesislikegraftforrotatorcuffrepairanapproachtofabricatehighlybiomimeticscaffoldcapableofzonespecificallyreleasingstemcelldifferentiationinducers AT muzhili engineeringanenthesislikegraftforrotatorcuffrepairanapproachtofabricatehighlybiomimeticscaffoldcapableofzonespecificallyreleasingstemcelldifferentiationinducers AT yangchen engineeringanenthesislikegraftforrotatorcuffrepairanapproachtofabricatehighlybiomimeticscaffoldcapableofzonespecificallyreleasingstemcelldifferentiationinducers AT taozhang engineeringanenthesislikegraftforrotatorcuffrepairanapproachtofabricatehighlybiomimeticscaffoldcapableofzonespecificallyreleasingstemcelldifferentiationinducers AT yanxu engineeringanenthesislikegraftforrotatorcuffrepairanapproachtofabricatehighlybiomimeticscaffoldcapableofzonespecificallyreleasingstemcelldifferentiationinducers AT yunjieliao engineeringanenthesislikegraftforrotatorcuffrepairanapproachtofabricatehighlybiomimeticscaffoldcapableofzonespecificallyreleasingstemcelldifferentiationinducers AT shulinding engineeringanenthesislikegraftforrotatorcuffrepairanapproachtofabricatehighlybiomimeticscaffoldcapableofzonespecificallyreleasingstemcelldifferentiationinducers AT zhanwenwang engineeringanenthesislikegraftforrotatorcuffrepairanapproachtofabricatehighlybiomimeticscaffoldcapableofzonespecificallyreleasingstemcelldifferentiationinducers AT xingli engineeringanenthesislikegraftforrotatorcuffrepairanapproachtofabricatehighlybiomimeticscaffoldcapableofzonespecificallyreleasingstemcelldifferentiationinducers AT chunfengzhao engineeringanenthesislikegraftforrotatorcuffrepairanapproachtofabricatehighlybiomimeticscaffoldcapableofzonespecificallyreleasingstemcelldifferentiationinducers AT lunquansun engineeringanenthesislikegraftforrotatorcuffrepairanapproachtofabricatehighlybiomimeticscaffoldcapableofzonespecificallyreleasingstemcelldifferentiationinducers AT jianzhonghu engineeringanenthesislikegraftforrotatorcuffrepairanapproachtofabricatehighlybiomimeticscaffoldcapableofzonespecificallyreleasingstemcelldifferentiationinducers AT hongbinlu engineeringanenthesislikegraftforrotatorcuffrepairanapproachtofabricatehighlybiomimeticscaffoldcapableofzonespecificallyreleasingstemcelldifferentiationinducers |