Genipin modified lyophilized platelet-rich fibrin scaffold for sustained release of growth factors to promote bone regeneration
Lyophilized platelet-rich fibrin (L-PRF) was shown to further activate resident platelets in platelet-rich fibrin causing a higher amount of growth factors release. However, it still required further experimental studies to resolve the uncontrolled degradation and burst release problem. In this stud...
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Frontiers Media S.A.
2022-09-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.1007692/full |
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author | Xiaoyao Liu Xiaoyao Liu Mingjing Yin Mingjing Yin Ying Li Jianqun Wang Junlong Da Zhongshuang Liu Kai Zhang Lixue Liu Wenxuan Zhang Peijun Wang Han Jin Bin Zhang Bin Zhang |
author_facet | Xiaoyao Liu Xiaoyao Liu Mingjing Yin Mingjing Yin Ying Li Jianqun Wang Junlong Da Zhongshuang Liu Kai Zhang Lixue Liu Wenxuan Zhang Peijun Wang Han Jin Bin Zhang Bin Zhang |
author_sort | Xiaoyao Liu |
collection | DOAJ |
description | Lyophilized platelet-rich fibrin (L-PRF) was shown to further activate resident platelets in platelet-rich fibrin causing a higher amount of growth factors release. However, it still required further experimental studies to resolve the uncontrolled degradation and burst release problem. In this study, the nature crosslinker genipin is introduced to improve the performance of L-PRF scaffold. We used a series of gradient concentration genipin solutions to react with L-PRF. The crosslinking degree, micro morphology, mean pore size, water absorption and mechanical properties of the crosslinked scaffold were evaluated. In order to study the effect of genipin modification on the release kinetics of growth factors from L-PRF, we detected the release of platelet-derived growth factor, vascular endothelial growth factor and transforming growth factor in vitro by ELISA. To investigate the biodegradability of the crosslinked L-PRF in vivo, the scaffolds were transplanted subcutaneously into backs of rats, and the materials were recovered at 1, 2 and 4 weeks after implantation. The biodegradation, inflammatory reaction and biocompatibility of the scaffolds were examined by histological staining. Finally, the genipin crosslinked/uncrosslinked L- Platelet-rich fibrin scaffolds were implanted with freshly prepared SHED cell sheets into rat critical size calvarial defects and the skull samples were recovered to examine the treatment efficacy of genipin crosslinked L-PRF by histologic and radiographic approaches. Results of this study indicated that genipin can be used to modify L-PRF at room temperature at a very low concentration. Genipin-modified L-PRF shows better biomechanical performance, slower biodegradation, good bioavailable and sustained release of growth factors. The 0.01% w/v and 0.1% w/v genipin crosslinked L-PRF have good porous structure and significantly promote cell proliferation and enhance the expression of key genes in osteogenesis in vitro, and work best in promoting bone regeneration in vivo. |
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spelling | doaj.art-4e1fb09a8d884cbbb6902e5d8cdc9dc52022-12-22T03:23:42ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-09-011310.3389/fphys.2022.10076921007692Genipin modified lyophilized platelet-rich fibrin scaffold for sustained release of growth factors to promote bone regenerationXiaoyao Liu0Xiaoyao Liu1Mingjing Yin2Mingjing Yin3Ying Li4Jianqun Wang5Junlong Da6Zhongshuang Liu7Kai Zhang8Lixue Liu9Wenxuan Zhang10Peijun Wang11Han Jin12Bin Zhang13Bin Zhang14Heilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Stomatology, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaHeilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Stomatology, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaHeilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaHeilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaHeilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Stomatology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, ChinaHeilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaHeilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaHeilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Stomatology, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaHeilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaHeilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaHeilongjiang Academy of Medical Sciences, Harbin, ChinaLyophilized platelet-rich fibrin (L-PRF) was shown to further activate resident platelets in platelet-rich fibrin causing a higher amount of growth factors release. However, it still required further experimental studies to resolve the uncontrolled degradation and burst release problem. In this study, the nature crosslinker genipin is introduced to improve the performance of L-PRF scaffold. We used a series of gradient concentration genipin solutions to react with L-PRF. The crosslinking degree, micro morphology, mean pore size, water absorption and mechanical properties of the crosslinked scaffold were evaluated. In order to study the effect of genipin modification on the release kinetics of growth factors from L-PRF, we detected the release of platelet-derived growth factor, vascular endothelial growth factor and transforming growth factor in vitro by ELISA. To investigate the biodegradability of the crosslinked L-PRF in vivo, the scaffolds were transplanted subcutaneously into backs of rats, and the materials were recovered at 1, 2 and 4 weeks after implantation. The biodegradation, inflammatory reaction and biocompatibility of the scaffolds were examined by histological staining. Finally, the genipin crosslinked/uncrosslinked L- Platelet-rich fibrin scaffolds were implanted with freshly prepared SHED cell sheets into rat critical size calvarial defects and the skull samples were recovered to examine the treatment efficacy of genipin crosslinked L-PRF by histologic and radiographic approaches. Results of this study indicated that genipin can be used to modify L-PRF at room temperature at a very low concentration. Genipin-modified L-PRF shows better biomechanical performance, slower biodegradation, good bioavailable and sustained release of growth factors. The 0.01% w/v and 0.1% w/v genipin crosslinked L-PRF have good porous structure and significantly promote cell proliferation and enhance the expression of key genes in osteogenesis in vitro, and work best in promoting bone regeneration in vivo.https://www.frontiersin.org/articles/10.3389/fphys.2022.1007692/fulllyophilized PRFgenipinsustained releasegrowth factorbone tissue engineering |
spellingShingle | Xiaoyao Liu Xiaoyao Liu Mingjing Yin Mingjing Yin Ying Li Jianqun Wang Junlong Da Zhongshuang Liu Kai Zhang Lixue Liu Wenxuan Zhang Peijun Wang Han Jin Bin Zhang Bin Zhang Genipin modified lyophilized platelet-rich fibrin scaffold for sustained release of growth factors to promote bone regeneration Frontiers in Physiology lyophilized PRF genipin sustained release growth factor bone tissue engineering |
title | Genipin modified lyophilized platelet-rich fibrin scaffold for sustained release of growth factors to promote bone regeneration |
title_full | Genipin modified lyophilized platelet-rich fibrin scaffold for sustained release of growth factors to promote bone regeneration |
title_fullStr | Genipin modified lyophilized platelet-rich fibrin scaffold for sustained release of growth factors to promote bone regeneration |
title_full_unstemmed | Genipin modified lyophilized platelet-rich fibrin scaffold for sustained release of growth factors to promote bone regeneration |
title_short | Genipin modified lyophilized platelet-rich fibrin scaffold for sustained release of growth factors to promote bone regeneration |
title_sort | genipin modified lyophilized platelet rich fibrin scaffold for sustained release of growth factors to promote bone regeneration |
topic | lyophilized PRF genipin sustained release growth factor bone tissue engineering |
url | https://www.frontiersin.org/articles/10.3389/fphys.2022.1007692/full |
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