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

[Display omitted] 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...

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Bibliographic Details
Published in:Acta biomaterialia 2018-04, Vol.71, p.168-183
Main Authors: Hu, Yejun, Ran, Jisheng, Zheng, Zefeng, Jin, Zhangchu, Chen, Xiao, Yin, Zi, Tang, Chenqi, Chen, Yangwu, Huang, Jiayun, Le, Huihui, Yan, Ruijian, Zhu, Ting, Wang, Junjuan, Lin, Junxin, Xu, Kan, Zhou, Yiting, Zhang, Wei, Cai, Youzhi, Dominique, Pioletti, Heng, Boon Chin, Chen, Weishan, Shen, Weiliang, Ouyang, Hong-Wei
Format: Article
Language:English
Subjects:
Animals
Anterior cruciate ligament
Anterior Cruciate Ligament - metabolism
Anterior Cruciate Ligament - pathology
Biocompatibility
Biomedical materials
Bone growth
Bone healing
Bone Regeneration - drug effects
Bones
Cartilage
Cartilage diseases
Cells (biology)
Chemokine CXCL12 - pharmacology
Collagen
Controlled release
CXCR4 protein
Degeneration
Disease Models, Animal
Fibroins - chemistry
Fibroins - pharmacology
Healing
In vivo methods and tests
Injection
Ligament derived stem cells
Ligaments
Osteoarthritis
Osteoarthritis, Knee - metabolism
Osteoarthritis, Knee - pathology
Osteoarthritis, Knee - therapy
Osteoprogenitor cells
Proteins
Rabbits
Regeneration
Regeneration (physiology)
Scaffolds
SDF-1 protein
SDF-1 releasing silk scaffold
Silk
Stem Cell Transplantation
Stem cells
Stiffness
Strategy
Synergistic effect
Tissue engineering
Tissue Scaffolds - chemistry
Transplantation
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Summary:[Display omitted] 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. 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. [Display omitted]
ISSN:1742-7061
1878-7568
DOI:10.1016/j.actbio.2018.02.019