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Transforming Growth Factor-β3/Recombinant Human-like Collagen/Chitosan Freeze-Dried Sponge Primed With Human Periodontal Ligament Stem Cells Promotes Bone Regeneration in Calvarial Defect Rats

Patients with a skull defect are at risk of developing cerebrospinal fluid leakage and ascending bacterial meningitis at >10% per year. However, treatment with stem cells has brought great hope to large-area cranial defects. Having found that transforming growth factor (TGF)-β3 can promote the os...

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Autores principales: Huang, Shiyi, Yu, Fenglin, Cheng, Yating, Li, Yangfan, Chen, Yini, Tang, Jianzhong, Bei, Yu, Tang, Qingxia, Zhao, Yueping, Huang, Yadong, Xiang, Qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103166/
https://www.ncbi.nlm.nih.gov/pubmed/33967817
http://dx.doi.org/10.3389/fphar.2021.678322
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author Huang, Shiyi
Yu, Fenglin
Cheng, Yating
Li, Yangfan
Chen, Yini
Tang, Jianzhong
Bei, Yu
Tang, Qingxia
Zhao, Yueping
Huang, Yadong
Xiang, Qi
author_facet Huang, Shiyi
Yu, Fenglin
Cheng, Yating
Li, Yangfan
Chen, Yini
Tang, Jianzhong
Bei, Yu
Tang, Qingxia
Zhao, Yueping
Huang, Yadong
Xiang, Qi
author_sort Huang, Shiyi
collection PubMed
description Patients with a skull defect are at risk of developing cerebrospinal fluid leakage and ascending bacterial meningitis at >10% per year. However, treatment with stem cells has brought great hope to large-area cranial defects. Having found that transforming growth factor (TGF)-β3 can promote the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), we designed a hybrid TGF-β3/recombinant human-like collagen recombinant human collagen/chitosan (CS) freeze-dried sponge (TRFS) loading hPDLSCs (TRFS-h) to repair skull defects in rats. CFS with 2% CS was selected based on the swelling degree, water absorption, and moisture retention. The CS freeze-dried sponge (CFS) formed a porous three-dimensional structure, as observed by scanning electron microscopy. In addition, cytotoxicity experiments and calcein-AM/PI staining showed that TRFS had a good cellular compatibility and could be degraded completely at 90 days in the implantation site. Furthermore, bone healing was evaluated using micro-computed tomography in rat skull defect models. The bone volume and bone volume fraction were higher in TRFS loaded with hPDLSCs (TRFS-h) group than in the controls (p < 0.01, vs. CFS or TRFS alone). The immunohistochemical results indicated that the expression of Runx2, BMP-2, and collagen-1 (COL Ⅰ) in cells surrounding bone defects in the experimental group was higher than those in the other groups (p < 0.01, vs. CFS or TRFS alone). Taken together, hPDLSCs could proliferate and undergo osteogenic differentiation in TRFS (p < 0.05), and TRFS-h accelerated bone repair in calvarial defect rats. Our research revealed that hPDLSCs could function as seeded cells for skull injury, and their osteogenic differentiation could be accelerated by TGF-β3. This represents an effective therapeutic strategy for restoring traumatic defects of the skull.
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spelling pubmed-81031662021-05-08 Transforming Growth Factor-β3/Recombinant Human-like Collagen/Chitosan Freeze-Dried Sponge Primed With Human Periodontal Ligament Stem Cells Promotes Bone Regeneration in Calvarial Defect Rats Huang, Shiyi Yu, Fenglin Cheng, Yating Li, Yangfan Chen, Yini Tang, Jianzhong Bei, Yu Tang, Qingxia Zhao, Yueping Huang, Yadong Xiang, Qi Front Pharmacol Pharmacology Patients with a skull defect are at risk of developing cerebrospinal fluid leakage and ascending bacterial meningitis at >10% per year. However, treatment with stem cells has brought great hope to large-area cranial defects. Having found that transforming growth factor (TGF)-β3 can promote the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), we designed a hybrid TGF-β3/recombinant human-like collagen recombinant human collagen/chitosan (CS) freeze-dried sponge (TRFS) loading hPDLSCs (TRFS-h) to repair skull defects in rats. CFS with 2% CS was selected based on the swelling degree, water absorption, and moisture retention. The CS freeze-dried sponge (CFS) formed a porous three-dimensional structure, as observed by scanning electron microscopy. In addition, cytotoxicity experiments and calcein-AM/PI staining showed that TRFS had a good cellular compatibility and could be degraded completely at 90 days in the implantation site. Furthermore, bone healing was evaluated using micro-computed tomography in rat skull defect models. The bone volume and bone volume fraction were higher in TRFS loaded with hPDLSCs (TRFS-h) group than in the controls (p < 0.01, vs. CFS or TRFS alone). The immunohistochemical results indicated that the expression of Runx2, BMP-2, and collagen-1 (COL Ⅰ) in cells surrounding bone defects in the experimental group was higher than those in the other groups (p < 0.01, vs. CFS or TRFS alone). Taken together, hPDLSCs could proliferate and undergo osteogenic differentiation in TRFS (p < 0.05), and TRFS-h accelerated bone repair in calvarial defect rats. Our research revealed that hPDLSCs could function as seeded cells for skull injury, and their osteogenic differentiation could be accelerated by TGF-β3. This represents an effective therapeutic strategy for restoring traumatic defects of the skull. Frontiers Media S.A. 2021-04-23 /pmc/articles/PMC8103166/ /pubmed/33967817 http://dx.doi.org/10.3389/fphar.2021.678322 Text en Copyright © 2021 Huang, Yu, Cheng, Li, Chen, Tang, Bei, Tang, Zhao, Huang and Xiang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Huang, Shiyi
Yu, Fenglin
Cheng, Yating
Li, Yangfan
Chen, Yini
Tang, Jianzhong
Bei, Yu
Tang, Qingxia
Zhao, Yueping
Huang, Yadong
Xiang, Qi
Transforming Growth Factor-β3/Recombinant Human-like Collagen/Chitosan Freeze-Dried Sponge Primed With Human Periodontal Ligament Stem Cells Promotes Bone Regeneration in Calvarial Defect Rats
title Transforming Growth Factor-β3/Recombinant Human-like Collagen/Chitosan Freeze-Dried Sponge Primed With Human Periodontal Ligament Stem Cells Promotes Bone Regeneration in Calvarial Defect Rats
title_full Transforming Growth Factor-β3/Recombinant Human-like Collagen/Chitosan Freeze-Dried Sponge Primed With Human Periodontal Ligament Stem Cells Promotes Bone Regeneration in Calvarial Defect Rats
title_fullStr Transforming Growth Factor-β3/Recombinant Human-like Collagen/Chitosan Freeze-Dried Sponge Primed With Human Periodontal Ligament Stem Cells Promotes Bone Regeneration in Calvarial Defect Rats
title_full_unstemmed Transforming Growth Factor-β3/Recombinant Human-like Collagen/Chitosan Freeze-Dried Sponge Primed With Human Periodontal Ligament Stem Cells Promotes Bone Regeneration in Calvarial Defect Rats
title_short Transforming Growth Factor-β3/Recombinant Human-like Collagen/Chitosan Freeze-Dried Sponge Primed With Human Periodontal Ligament Stem Cells Promotes Bone Regeneration in Calvarial Defect Rats
title_sort transforming growth factor-β3/recombinant human-like collagen/chitosan freeze-dried sponge primed with human periodontal ligament stem cells promotes bone regeneration in calvarial defect rats
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103166/
https://www.ncbi.nlm.nih.gov/pubmed/33967817
http://dx.doi.org/10.3389/fphar.2021.678322
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