Adipose-derived stem cell spheroid-laden microbial transglutaminase cross-linked gelatin hydrogel for treating diabetic periodontal wounds and craniofacial defects

Abstract Background Diabetes mellitus deteriorates the destruction and impairs the healing of periodontal wounds and craniofacial defects. This study is to evaluate the potential of self-assembled adipose-derived stem cell spheroids (ADsp) in microbial transglutaminase cross-linked gelatin hydrogel...

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Main Authors: Che-Chang Tu, Nai-Chen Cheng, Jiashing Yu, Yi-Xuan Pan, Wei-Chiu Tai, Yin-Chuan Chen, Po-Chun Chang
Format: Article
Language:English
Published: BMC 2023-02-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-023-03238-2
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author Che-Chang Tu
Nai-Chen Cheng
Jiashing Yu
Yi-Xuan Pan
Wei-Chiu Tai
Yin-Chuan Chen
Po-Chun Chang
author_facet Che-Chang Tu
Nai-Chen Cheng
Jiashing Yu
Yi-Xuan Pan
Wei-Chiu Tai
Yin-Chuan Chen
Po-Chun Chang
author_sort Che-Chang Tu
collection DOAJ
description Abstract Background Diabetes mellitus deteriorates the destruction and impairs the healing of periodontal wounds and craniofacial defects. This study is to evaluate the potential of self-assembled adipose-derived stem cell spheroids (ADsp) in microbial transglutaminase cross-linked gelatin hydrogel (mTG) for treating diabetic periodontal wounds and craniofacial defects. Methods Human adipose-derived stem cells (ADSCs) were isolated by lipoaspiration, pluripotent genes and trilineage differentiation were examined, and the maintenance of ADsp properties in mTG was verified. Oral mucosal wounds and calvarial osseous defects were created in diabetic rats. Gross observation, histologic evaluation, and immunohistochemistry for proliferating cells and keratinization were conducted in the mucosal wounds within 4–28 days. Micro-CT imaging, histologic evaluation, and immunohistochemistry for proliferating cells and osteogenic differentiation were conducted in the osseous defects at 7 and 28 days. Results ADSCs expressed pluripotent genes and were capable of trilineage differentiation. ADsp retained morphology and stemness in mTG. In diabetic mucosal wounds, wound closure, epithelization, and keratinization were accelerated in those with ADsp and ADsp-mTG. In diabetic osseous defects, osteogenic differentiation markers were evidently expressed, cell proliferation was promoted from day 7, and bone formation was significantly promoted at day 28 in those with osteogenically pretreated ADsp-mTG. Conclusions ADsp-mTG accelerated diabetic oral mucosal wound healing, and osteogenically pretreated ADsp-mTG promoted diabetic osseous defect regeneration, proving that ADsp-mTG facilitated diabetic periodontal wound healing and craniofacial osseous defect regeneration.
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spelling doaj.art-6a0d401cd5cc4229976a9dacd4df72bf2023-02-05T12:06:09ZengBMCStem Cell Research & Therapy1757-65122023-02-0114111410.1186/s13287-023-03238-2Adipose-derived stem cell spheroid-laden microbial transglutaminase cross-linked gelatin hydrogel for treating diabetic periodontal wounds and craniofacial defectsChe-Chang Tu0Nai-Chen Cheng1Jiashing Yu2Yi-Xuan Pan3Wei-Chiu Tai4Yin-Chuan Chen5Po-Chun Chang6Graduate Institute of Clinical Dentistry, School of Dentistry, College of Medicine, National Taiwan UniversityDepartment of Surgery, National Taiwan University Hospital and College of MedicineDepartment of Chemical Engineering, College of Engineering, National Taiwan UniversityDivision of Periodontics, Department of Dentistry, National Taiwan University HospitalGraduate Institute of Clinical Dentistry, School of Dentistry, College of Medicine, National Taiwan UniversityDepartment of Chemical Engineering, College of Engineering, National Taiwan UniversityGraduate Institute of Clinical Dentistry, School of Dentistry, College of Medicine, National Taiwan UniversityAbstract Background Diabetes mellitus deteriorates the destruction and impairs the healing of periodontal wounds and craniofacial defects. This study is to evaluate the potential of self-assembled adipose-derived stem cell spheroids (ADsp) in microbial transglutaminase cross-linked gelatin hydrogel (mTG) for treating diabetic periodontal wounds and craniofacial defects. Methods Human adipose-derived stem cells (ADSCs) were isolated by lipoaspiration, pluripotent genes and trilineage differentiation were examined, and the maintenance of ADsp properties in mTG was verified. Oral mucosal wounds and calvarial osseous defects were created in diabetic rats. Gross observation, histologic evaluation, and immunohistochemistry for proliferating cells and keratinization were conducted in the mucosal wounds within 4–28 days. Micro-CT imaging, histologic evaluation, and immunohistochemistry for proliferating cells and osteogenic differentiation were conducted in the osseous defects at 7 and 28 days. Results ADSCs expressed pluripotent genes and were capable of trilineage differentiation. ADsp retained morphology and stemness in mTG. In diabetic mucosal wounds, wound closure, epithelization, and keratinization were accelerated in those with ADsp and ADsp-mTG. In diabetic osseous defects, osteogenic differentiation markers were evidently expressed, cell proliferation was promoted from day 7, and bone formation was significantly promoted at day 28 in those with osteogenically pretreated ADsp-mTG. Conclusions ADsp-mTG accelerated diabetic oral mucosal wound healing, and osteogenically pretreated ADsp-mTG promoted diabetic osseous defect regeneration, proving that ADsp-mTG facilitated diabetic periodontal wound healing and craniofacial osseous defect regeneration.https://doi.org/10.1186/s13287-023-03238-2Mesenchymal stem cellDiabetesWound healingTissue engineeringBone regenerationHydrogels
spellingShingle Che-Chang Tu
Nai-Chen Cheng
Jiashing Yu
Yi-Xuan Pan
Wei-Chiu Tai
Yin-Chuan Chen
Po-Chun Chang
Adipose-derived stem cell spheroid-laden microbial transglutaminase cross-linked gelatin hydrogel for treating diabetic periodontal wounds and craniofacial defects
Stem Cell Research & Therapy
Mesenchymal stem cell
Diabetes
Wound healing
Tissue engineering
Bone regeneration
Hydrogels
title Adipose-derived stem cell spheroid-laden microbial transglutaminase cross-linked gelatin hydrogel for treating diabetic periodontal wounds and craniofacial defects
title_full Adipose-derived stem cell spheroid-laden microbial transglutaminase cross-linked gelatin hydrogel for treating diabetic periodontal wounds and craniofacial defects
title_fullStr Adipose-derived stem cell spheroid-laden microbial transglutaminase cross-linked gelatin hydrogel for treating diabetic periodontal wounds and craniofacial defects
title_full_unstemmed Adipose-derived stem cell spheroid-laden microbial transglutaminase cross-linked gelatin hydrogel for treating diabetic periodontal wounds and craniofacial defects
title_short Adipose-derived stem cell spheroid-laden microbial transglutaminase cross-linked gelatin hydrogel for treating diabetic periodontal wounds and craniofacial defects
title_sort adipose derived stem cell spheroid laden microbial transglutaminase cross linked gelatin hydrogel for treating diabetic periodontal wounds and craniofacial defects
topic Mesenchymal stem cell
Diabetes
Wound healing
Tissue engineering
Bone regeneration
Hydrogels
url https://doi.org/10.1186/s13287-023-03238-2
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