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Exogenous stromal derived factor-1 releasing silk scaffold combined with intra-articular injection of progenitor cells promotes bone-ligament-bone regeneration.
Journal article

Exogenous stromal derived factor-1 releasing silk scaffold combined with intra-articular injection of progenitor cells promotes bone-ligament-bone regeneration.

  • Hu Y Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, China; Department of Sports Medicine, School of Medicine, Zhejiang University, China.
  • Ran J Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China; Orthopaedics Research Institute of Zhejiang University, China.
  • Zheng Z Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China.
  • Jin Z Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, China.
  • Chen X Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, China; Department of Sports Medicine, School of Medicine, Zhejiang University, China; China Orthopaedic Regenerative Medicine (CORMed), Hangzhou, China.
  • Yin Z Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, China; Department of Sports Medicine, School of Medicine, Zhejiang University, China.
  • Tang C Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China.
  • Chen Y Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China.
  • Huang J Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China.
  • Le H Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China.
  • Yan R Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China.
  • Zhu T Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China.
  • Wang J Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, China.
  • Lin J Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, China.
  • Xu K Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China.
  • Zhou Y Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 310003 Hangzhou, China.
  • Zhang W Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China; Orthopaedics Research Institute of Zhejiang University, China.
  • Cai Y Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, China.
  • Dominique P Laboratory of Biomechanical Orthopedics, EPFL, Lausanne, Switzerland.
  • Heng BC Department of Endodontology, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong; Department of Biological Sciences, Faculty of Science and Technology, Sunway University, Bandar Sunway, Selangor Darul Ehsan, Malaysia.
  • Chen W Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China; Orthopaedics Research Institute of Zhejiang University, China.
  • Shen W Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, China; Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China; Orthopaedics Research Institute of Zhejiang University, China; Department of Sports Medicine, School of Medicine, Zhejiang University, China; China Orthopaedic Regenerative Medicine (CORMed), Hangzhou, China. Electronic address: wlshen@zju.edu.cn.
  • Ouyang HW Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, China; Department of Sports Medicine, School of Medicine, Zhejiang University, China; China Orthopaedic Regenerative Medicine (CORMed), Hangzhou, China. Electronic address: hwoy@zju.edu.cn.
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  • 2018-03-11
Published in:
  • Acta biomaterialia. - 2018
Anterior cruciate ligament
Ligament derived stem cells
Regeneration
SDF-1 releasing silk scaffold
Tissue engineering
Animals
Anterior Cruciate Ligament
Bone Regeneration
Chemokine CXCL12
Disease Models, Animal
Fibroins
Osteoarthritis, Knee
Rabbits
Stem Cell Transplantation
Tissue Scaffolds
English Anterior cruciate ligament (ACL) is one of the most difficult tissues to heal once injured. Ligament regeneration and tendon-bone junction healing are two major goals of ACL reconstruction. This study aimed to investigate the synergistic therapeutic effects of Stromal cell-derived factor 1 (SDF-1)-releasing collagen-silk (CSF) scaffold combined with intra-articular injection of ligament-derived stem/progenitor cells (LSPCs) for ACL regeneration and the amelioration in the long-term complication of osteoarthritis (OA). The stem cell recruitment ability of CSF scaffold and the multipotency, particularly the tendon forming ability of LSPCs from rabbits were characterized in vitro, while the synergistic effect of the CSF scaffold and LSPCs for ACL regeneration and OA amelioration were investigated in vivo at 1, 3, and 6 months with a rabbit ACL reconstruction model. The CSF scaffold was used as a substitute for the ACL, and LSPCs were injected into the joint cavity after 7 days of the ACL reconstruction. CSF scaffold displayed a controlled release pattern for the encapsulated protein for up to 7 days with an increased stiffness in the mechanical property. LSPCs, which exhibited highly I Collagen and CXCR4 expression, were attracted by SDF-1 and successfully relocated into the CSF scaffold at 1 month in vivo. At 3 and 6 months post-treatment, the CSF scaffold combined with LSPCs (CSFL group) enhanced the regeneration of ACL tissue, and promoted bone tunnel healing. Furthermore, the OA progression was impeded efficiently. Our findings here provided a new strategy that using stem cell recruiting CSF scaffold with tissue-specific stem cells, could be a promising solution for ACL regeneration.


STATEMENT OF SIGNIFICANCE
In this study, we developed a silk scaffold with increased stiffness and SDF-1 controlled release capacity for ligament repair. This advanced scaffold transplantation combined with intra-articular injection of LSPCs (which was isolated from rabbit ligament for the first time in this study) promoted the regeneration of both the tendinous and bone tunnel portion of ACL. This therapeutic strategy also ameliorated cartilage degeneration and reduced the severity of arthrofibrosis. Hence, combining LSPCs injection with SDF-1-releasing silk scaffold is demonstrated as a therapeutic strategy for ACL regeneration and OA treatment in the clinic.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/99576
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