The application of human periodontal ligament stem cells and biomimetic silk scaffold for in situ tendon regeneration

Abstract Background With the development of tissue engineering, enhanced tendon regeneration could be achieved by exploiting suitable cell types and biomaterials. The accessibility, robust cell amplification ability, superior tendon differentiation potential, and immunomodulatory effects of human pe...

Full description

Bibliographic Details
Main Authors: Jialin Chen, Qingyun Mo, Renwang Sheng, Aijing Zhu, Chen Ling, Yifan Luo, Aini Zhang, Zhixuan Chen, Qingqiang Yao, Zhuoying Cai, Wei Zhang
Format: Article
Language:English
Published: BMC 2021-12-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-021-02661-7
_version_ 1818574531289153536
author Jialin Chen
Qingyun Mo
Renwang Sheng
Aijing Zhu
Chen Ling
Yifan Luo
Aini Zhang
Zhixuan Chen
Qingqiang Yao
Zhuoying Cai
Wei Zhang
author_facet Jialin Chen
Qingyun Mo
Renwang Sheng
Aijing Zhu
Chen Ling
Yifan Luo
Aini Zhang
Zhixuan Chen
Qingqiang Yao
Zhuoying Cai
Wei Zhang
author_sort Jialin Chen
collection DOAJ
description Abstract Background With the development of tissue engineering, enhanced tendon regeneration could be achieved by exploiting suitable cell types and biomaterials. The accessibility, robust cell amplification ability, superior tendon differentiation potential, and immunomodulatory effects of human periodontal ligament stem cells (hPDLSCs) indicate their potential as ideal seed cells for tendon tissue engineering. Nevertheless, there are currently no reports of using PDLSCs as seed cells. Previous studies have confirmed the potential of silk scaffold for tendon tissue engineering. However, the biomimetic silk scaffold with tendon extracellular matrix (ECM)-like structure has not been systematically studied for in situ tendon regeneration. Therefore, this study aims to evaluate the effects of hPDLSCs and biomimetic silk scaffold on in situ tendon regeneration. Methods Human PDLSCs were isolated from extracted wisdom teeth. The differentiation potential of hPDLSCs towards osteo-, chondro-, and adipo-lineage was examined by cultured in different inducing media. Aligned and random silk scaffolds were fabricated by the controlled directional freezing technique. Scaffolds were characterized including surface structure, water contact angle, swelling ratio, degradation speed and mechanical properties. The biocompatibility of silk scaffolds was evaluated by live/dead staining, SEM observation, cell proliferation determination and immunofluorescent staining of deposited collagen type I. Subsequently, hPDLSCs were seeded on the aligned silk scaffold and transplanted into the ruptured rat Achilles tendon. Scaffolds without cells served as control groups. After 4 weeks, histology evaluation was carried out and macrophage polarization was examined to check the repair effects and immunomodulatory effects. Results Human PDLSCs were successfully isolated, and their multi-differentiation potential was confirmed. Compared with random scaffold, aligned silk scaffold had more elongated and aligned pores and promoted the proliferation and ordered arrangement of hPDLSCs. After implantation into rat Achilles tendon defect, hPDLSCs seeded aligned silk scaffold enhanced tendon repair with more tendon-like tissue formation after 4 weeks, as compared to the scaffold-only groups. Higher expression of CD206 and lower expression of iNOS, IL-1β and TNF-α were found in the hPDLSCs seeded aligned silk scaffold group, which revealed its modulation effect of macrophage polarization from M1 to M2 phenotype. Conclusions In summary, this study demonstrates the efficacy of hPDLSCs as seed cells and aligned silk scaffold as a tendon-mimetic scaffold for enhanced tendon tissue engineering, which may have broad implications for future tendon tissue engineering and regenerative medicine researches.
first_indexed 2024-12-15T00:27:52Z
format Article
id doaj.art-89966c7f2bae4ec495c47a4040e848d1
institution Directory Open Access Journal
issn 1757-6512
language English
last_indexed 2024-12-15T00:27:52Z
publishDate 2021-12-01
publisher BMC
record_format Article
series Stem Cell Research & Therapy
spelling doaj.art-89966c7f2bae4ec495c47a4040e848d12022-12-21T22:42:07ZengBMCStem Cell Research & Therapy1757-65122021-12-0112111510.1186/s13287-021-02661-7The application of human periodontal ligament stem cells and biomimetic silk scaffold for in situ tendon regenerationJialin Chen0Qingyun Mo1Renwang Sheng2Aijing Zhu3Chen Ling4Yifan Luo5Aini Zhang6Zhixuan Chen7Qingqiang Yao8Zhuoying Cai9Wei Zhang10School of Medicine, Southeast UniversitySchool of Medicine, Southeast UniversitySchool of Medicine, Southeast UniversitySchool of Medicine, Southeast UniversityDepartment of Orthopaedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical UniversitySchool of Medicine, Southeast UniversitySchool of Medicine, Southeast UniversitySchool of Medicine, Southeast UniversityChina Orthopedic Regenerative Medicine Group (CORMed)Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Zhejiang UniversitySchool of Medicine, Southeast UniversityAbstract Background With the development of tissue engineering, enhanced tendon regeneration could be achieved by exploiting suitable cell types and biomaterials. The accessibility, robust cell amplification ability, superior tendon differentiation potential, and immunomodulatory effects of human periodontal ligament stem cells (hPDLSCs) indicate their potential as ideal seed cells for tendon tissue engineering. Nevertheless, there are currently no reports of using PDLSCs as seed cells. Previous studies have confirmed the potential of silk scaffold for tendon tissue engineering. However, the biomimetic silk scaffold with tendon extracellular matrix (ECM)-like structure has not been systematically studied for in situ tendon regeneration. Therefore, this study aims to evaluate the effects of hPDLSCs and biomimetic silk scaffold on in situ tendon regeneration. Methods Human PDLSCs were isolated from extracted wisdom teeth. The differentiation potential of hPDLSCs towards osteo-, chondro-, and adipo-lineage was examined by cultured in different inducing media. Aligned and random silk scaffolds were fabricated by the controlled directional freezing technique. Scaffolds were characterized including surface structure, water contact angle, swelling ratio, degradation speed and mechanical properties. The biocompatibility of silk scaffolds was evaluated by live/dead staining, SEM observation, cell proliferation determination and immunofluorescent staining of deposited collagen type I. Subsequently, hPDLSCs were seeded on the aligned silk scaffold and transplanted into the ruptured rat Achilles tendon. Scaffolds without cells served as control groups. After 4 weeks, histology evaluation was carried out and macrophage polarization was examined to check the repair effects and immunomodulatory effects. Results Human PDLSCs were successfully isolated, and their multi-differentiation potential was confirmed. Compared with random scaffold, aligned silk scaffold had more elongated and aligned pores and promoted the proliferation and ordered arrangement of hPDLSCs. After implantation into rat Achilles tendon defect, hPDLSCs seeded aligned silk scaffold enhanced tendon repair with more tendon-like tissue formation after 4 weeks, as compared to the scaffold-only groups. Higher expression of CD206 and lower expression of iNOS, IL-1β and TNF-α were found in the hPDLSCs seeded aligned silk scaffold group, which revealed its modulation effect of macrophage polarization from M1 to M2 phenotype. Conclusions In summary, this study demonstrates the efficacy of hPDLSCs as seed cells and aligned silk scaffold as a tendon-mimetic scaffold for enhanced tendon tissue engineering, which may have broad implications for future tendon tissue engineering and regenerative medicine researches.https://doi.org/10.1186/s13287-021-02661-7PDLSCsSilkBiomimetic scaffoldTendon repairTissue regeneration
spellingShingle Jialin Chen
Qingyun Mo
Renwang Sheng
Aijing Zhu
Chen Ling
Yifan Luo
Aini Zhang
Zhixuan Chen
Qingqiang Yao
Zhuoying Cai
Wei Zhang
The application of human periodontal ligament stem cells and biomimetic silk scaffold for in situ tendon regeneration
Stem Cell Research & Therapy
PDLSCs
Silk
Biomimetic scaffold
Tendon repair
Tissue regeneration
title The application of human periodontal ligament stem cells and biomimetic silk scaffold for in situ tendon regeneration
title_full The application of human periodontal ligament stem cells and biomimetic silk scaffold for in situ tendon regeneration
title_fullStr The application of human periodontal ligament stem cells and biomimetic silk scaffold for in situ tendon regeneration
title_full_unstemmed The application of human periodontal ligament stem cells and biomimetic silk scaffold for in situ tendon regeneration
title_short The application of human periodontal ligament stem cells and biomimetic silk scaffold for in situ tendon regeneration
title_sort application of human periodontal ligament stem cells and biomimetic silk scaffold for in situ tendon regeneration
topic PDLSCs
Silk
Biomimetic scaffold
Tendon repair
Tissue regeneration
url https://doi.org/10.1186/s13287-021-02661-7
work_keys_str_mv AT jialinchen theapplicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT qingyunmo theapplicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT renwangsheng theapplicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT aijingzhu theapplicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT chenling theapplicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT yifanluo theapplicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT ainizhang theapplicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT zhixuanchen theapplicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT qingqiangyao theapplicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT zhuoyingcai theapplicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT weizhang theapplicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT jialinchen applicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT qingyunmo applicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT renwangsheng applicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT aijingzhu applicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT chenling applicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT yifanluo applicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT ainizhang applicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT zhixuanchen applicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT qingqiangyao applicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT zhuoyingcai applicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration
AT weizhang applicationofhumanperiodontalligamentstemcellsandbiomimeticsilkscaffoldforinsitutendonregeneration