Notch Signaling Hydrogels Enable Rapid Vascularization and Promote Dental Pulp Tissue Regeneration

Author:

Zhang Siyuan1,Yu Mei1,Li Maojiao2,He Min1,Xie Li1,Huo Fangjun1ORCID,Tian Weidong2

Affiliation:

1. State Key Laboratory of Oral Diseases National Clinical Research Center for Oral Diseases National Engineering Laboratory for Oral Regenerative Medicine Engineering Research Center of Oral Translational Medicine Ministry of Education West China Hospital of Stomatology Sichuan University Chengdu 610041 P. R. China

2. State Key Laboratory of Oral Diseases National Clinical Research Center for Oral Diseases National Engineering Laboratory for Oral Regenerative Medicine Engineering Research Center of Oral Translational Medicine Ministry of Education Department of Oral and Maxillofacial Surgery West China Hospital of Stomatology Sichuan University Chengdu 610041 P. R. China

Abstract

AbstractSuccessful dental pulp regeneration is closely associated with rapid revascularization and angiogenesis, processes driven by the Jagged1(JAG1)/Notch signaling pathway. However, soluble Notch ligands have proven ineffective in activating this pathway. To overcome this limitation, a Notch signaling hydrogel is developed by indirectly immobilizing JAG1, aimed at precisely directing the regeneration of vascularized pulp tissue. This hydrogel displays favorable mechanical properties and biocompatibility. Cultivating dental pulp stem cells (DPSCs) and endothelial cells (ECs) on this hydrogel significantly upregulate Notch target genes and key proangiogenic markers expression. Three‐dimensional (3D) culture assays demonstrate Notch signaling hydrogels improve effectiveness by facilitating encapsulated cell differentiation, enhancing their paracrine functions, and promoting capillary lumen formation. Furthermore, it effectively communicates with the Wnt signaling pathway, creating an odontoinductive microenvironment for pulp‐dentin complex formation. In vivo studies show that short‐term transplantation of the Notch signaling hydrogel accelerates angiogenesis, stabilizes capillary‐like structures, and improves cell survival. Long‐term transplantation further confirms its capability to promote the formation of pulp‐like tissues rich in blood vessels and peripheral nerve‐like structures. In conclusion, this study introduces a feasible and effective hydrogel tailored to specifically regulate the JAG1/Notch signaling pathway, showing potential in advancing regenerative strategies for dental pulp tissue.

Funder

National Basic Research Program of China

National Natural Science Foundation of China

West China Hospital, Sichuan University

Sichuan Province Science and Technology Support Program

Publisher

Wiley

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3