Vascularized pulp regeneration via injecting simvastatin functionalized GelMA cryogel microspheres loaded with stem cells from human exfoliated deciduous teeth

Xiaojing Yuan; Zuoying Yuan; Yuanyuan Wang; Zhuo Wan; Xiaotong Wang; Shi Yu; Jianmin Han; Jianyong Huang; Chunyang Xiong; Lihong Ge; Qing Cai; Yuming Zhao

Materials Today Bio (Jan 2022)

Vascularized pulp regeneration via injecting simvastatin functionalized GelMA cryogel microspheres loaded with stem cells from human exfoliated deciduous teeth

Xiaojing Yuan,
Zuoying Yuan,
Yuanyuan Wang,
Zhuo Wan,
Xiaotong Wang,
Shi Yu,
Jianmin Han,
Jianyong Huang,
Chunyang Xiong,
Lihong Ge,
Qing Cai,
Yuming Zhao

Affiliations

Xiaojing Yuan: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China
Zuoying Yuan: Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, 100871, China
Yuanyuan Wang: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China
Zhuo Wan: State Key Laboratory of Organic-Inorganic Composites; Beijing Laboratory of Biomedical Materials; Beijing University of Chemical Technology, Beijing, 100029, China
Xiaotong Wang: Department of Emergency, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China
Shi Yu: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China
Jianmin Han: Dental Medical Devices Testing Center, Dental Materials Laboratory, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China
Jianyong Huang: Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, 100871, China
Chunyang Xiong: Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, 100871, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China; Corresponding author. Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, 100871, China.
Lihong Ge: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China; Corresponding author. Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China.
Qing Cai: State Key Laboratory of Organic-Inorganic Composites; Beijing Laboratory of Biomedical Materials; Beijing University of Chemical Technology, Beijing, 100029, China
Yuming Zhao: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China; Corresponding author. Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China.

Journal volume & issue: Vol. 13
p. 100209

Abstract

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Dental pulp necrosis are serious pathologic entities that causes tooth nutrition deficiency and abnormal root development, while regeneration of functional pulp tissue is of paramount importance to regain tooth vitality. However, existing clinical treatments, which focus on replacing the necrotic pulp tissue with inactive filling materials, fail to restore pulp vitality and functions, thus resulting in a devitalized and weakened tooth. Currently, dental pulp regeneration via stem cell-based therapy for pulpless teeth has raised enormous attention to restore the functional pulp. Here, a novel design of injectable simvastatin (SIM) functionalized gelatin methacrylate (GelMA) cryogel microspheres (SMS) loaded with stem cells from human exfoliated deciduous teeth (SHEDs) was established to refine SHEDs biological behaviors and promote in vivo vascularized pulp-like tissue regeneration. In this system, SIM encapsulated poly (lactide-co-glycolide) (PLGA) nanoparticles were incorporated into GelMA cryogel microspheres via cryogelation and O1/W/O2 emulsion method. SMS with sustained release of SIM promoted SHEDs adhesion, proliferation and exhibited cell protection properties during the injection process. Furthermore, SMS enhanced SHEDs odontogenic differentiation and angiogenic potential, and SHEDs loaded SMS (SHEDs/SMS) are beneficial for human umbilical vein endothelial cells (HUVECs) migration and angiogenesis, demonstrating their potential for use in promoting vascularized tissue regeneration. SHEDs/SMS complexes were injected into cleaned human tooth root segments for subcutaneous implantation in nude mice. Our results demonstrated that SHEDs/SMS could induce vessel-rich pulp-like tissue regeneration in vivo and that such an injectable nano-in-micro multistage system for the controlled delivery of bioactive reagents would be suitable for clinical application in endodontic regenerative dentistry.

Published in Materials Today Bio

ISSN: 2590-0064 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: https://www.journals.elsevier.com/materials-today-bio

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