The paradigm shifts of periodontal regeneration strategy: From reparative manipulation to developmental engineering

Ideal periodontal regeneration requires the integration of alveolar bone, periodontal ligament, and cementum, along with Sharpey's fibers for occlusal force resistance. However, physiological regeneration remains rare due to its intricate structure, making clinical regeneration a challenge. Per...

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Main Authors: Guanqi Liu, Junlong Xue, Xuan Zhou, Mixiao Gui, Ruidi Xia, Yanshu Zhang, Yihua Cai, Shuhua Li, Songtao Shi, Xueli Mao, Zetao Chen
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-07-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X25001112
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author Guanqi Liu
Junlong Xue
Xuan Zhou
Mixiao Gui
Ruidi Xia
Yanshu Zhang
Yihua Cai
Shuhua Li
Songtao Shi
Xueli Mao
Zetao Chen
author_facet Guanqi Liu
Junlong Xue
Xuan Zhou
Mixiao Gui
Ruidi Xia
Yanshu Zhang
Yihua Cai
Shuhua Li
Songtao Shi
Xueli Mao
Zetao Chen
author_sort Guanqi Liu
collection DOAJ
description Ideal periodontal regeneration requires the integration of alveolar bone, periodontal ligament, and cementum, along with Sharpey's fibers for occlusal force resistance. However, physiological regeneration remains rare due to its intricate structure, making clinical regeneration a challenge. Periodontal ligament stem cells (PDLSCs), first isolated in 2004, hold the key to multi-directional differentiation into cementoblasts, fibroblasts, and osteoblasts. While traditional therapies like guided tissue regeneration (GTR) aim to activate PDLSCs, clinical outcomes are inconsistent, suggesting the need for additional strategies to enhance PDLSCs' functions. Advancements in molecular biotechnology have introduced the use of recombinant growth factors for tissue regeneration. However, maintaining their efficacy requires high doses, posing cost and safety issues. Multi-layered scaffolds combined with cell sheet technology offer new insights, but face production, ethical, and survival challenges. Immune regulation plays a crucial role in PDLSC-mediated regeneration. The concept of “coagulo-immunomodulation” has emerged, emphasizing the coupling of blood coagulation and immune responses for periodontal regeneration. Despite its potential, the clinical translation of immune-based strategies remains elusive. The “developmental engineering” approach, which mimics developmental events using embryonic-stage cells and microenvironments, shows promise. Our research group has made initial strides, indicating its potential as a viable solution for periodontal complex regeneration. However, further clinical trials and considerations are needed for successful clinical application. This review aims to summarize the strategic transitions in the development of periodontal regenerative materials and to propose prospective avenues for future development.
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spelling doaj-art-1a0aab87711f49ab906d4caffd0f8db62025-08-20T02:07:40ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-07-014941843610.1016/j.bioactmat.2025.03.009The paradigm shifts of periodontal regeneration strategy: From reparative manipulation to developmental engineeringGuanqi Liu0Junlong Xue1Xuan Zhou2Mixiao Gui3Ruidi Xia4Yanshu Zhang5Yihua Cai6Shuhua Li7Songtao Shi8Xueli Mao9Zetao Chen10Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China; Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China; Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China; Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China; Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China; Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China; Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China; Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China; Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China; South China Center of Craniofacial Stem Cell Research, Guangzhou, 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China; South China Center of Craniofacial Stem Cell Research, Guangzhou, 510055, China; Corresponding author. Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China.Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China; Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, China; Corresponding author. Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China.Ideal periodontal regeneration requires the integration of alveolar bone, periodontal ligament, and cementum, along with Sharpey's fibers for occlusal force resistance. However, physiological regeneration remains rare due to its intricate structure, making clinical regeneration a challenge. Periodontal ligament stem cells (PDLSCs), first isolated in 2004, hold the key to multi-directional differentiation into cementoblasts, fibroblasts, and osteoblasts. While traditional therapies like guided tissue regeneration (GTR) aim to activate PDLSCs, clinical outcomes are inconsistent, suggesting the need for additional strategies to enhance PDLSCs' functions. Advancements in molecular biotechnology have introduced the use of recombinant growth factors for tissue regeneration. However, maintaining their efficacy requires high doses, posing cost and safety issues. Multi-layered scaffolds combined with cell sheet technology offer new insights, but face production, ethical, and survival challenges. Immune regulation plays a crucial role in PDLSC-mediated regeneration. The concept of “coagulo-immunomodulation” has emerged, emphasizing the coupling of blood coagulation and immune responses for periodontal regeneration. Despite its potential, the clinical translation of immune-based strategies remains elusive. The “developmental engineering” approach, which mimics developmental events using embryonic-stage cells and microenvironments, shows promise. Our research group has made initial strides, indicating its potential as a viable solution for periodontal complex regeneration. However, further clinical trials and considerations are needed for successful clinical application. This review aims to summarize the strategic transitions in the development of periodontal regenerative materials and to propose prospective avenues for future development.http://www.sciencedirect.com/science/article/pii/S2452199X25001112Periodontal regenerationDevelopmental engineeringImmune microenvironmentBiomaterials
spellingShingle Guanqi Liu
Junlong Xue
Xuan Zhou
Mixiao Gui
Ruidi Xia
Yanshu Zhang
Yihua Cai
Shuhua Li
Songtao Shi
Xueli Mao
Zetao Chen
The paradigm shifts of periodontal regeneration strategy: From reparative manipulation to developmental engineering
Bioactive Materials
Periodontal regeneration
Developmental engineering
Immune microenvironment
Biomaterials
title The paradigm shifts of periodontal regeneration strategy: From reparative manipulation to developmental engineering
title_full The paradigm shifts of periodontal regeneration strategy: From reparative manipulation to developmental engineering
title_fullStr The paradigm shifts of periodontal regeneration strategy: From reparative manipulation to developmental engineering
title_full_unstemmed The paradigm shifts of periodontal regeneration strategy: From reparative manipulation to developmental engineering
title_short The paradigm shifts of periodontal regeneration strategy: From reparative manipulation to developmental engineering
title_sort paradigm shifts of periodontal regeneration strategy from reparative manipulation to developmental engineering
topic Periodontal regeneration
Developmental engineering
Immune microenvironment
Biomaterials
url http://www.sciencedirect.com/science/article/pii/S2452199X25001112
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