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

Materials Today Bio

Qing Cai¹  Xiaotong Wang¹  Zuoying Yuan²  Jianyong Huang²  Yuanyuan Wang³  Chunyang Xiong³  Lihong Ge⁴  Zhuo Wan⁴  Shi Yu⁵  Xiaojing Yuan⁶  Jianmin Han⁶  Yuming Zhao⁷ 

[1] Beijing Key Laboratory of Digital Stomatology, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China;;National Center of Stomatology &;National Clinical Research Center for Oral Diseases &;National Engineering Laboratory for Digital and Material Technology of Stomatology &Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, 100871, China;;Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology &State Key Laboratory of Organic-Inorganic Composites;

关键词: Pulp regeneration;    Stem cells from human exfoliated deciduous teeth;    Simvastatin;    Controlled delivery;    Cryogel microspheres;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown