Effect of hUCMSC-sEV-Loaded GelMA Microspheres on Pulp/Dentin Repair and Regeneration

  • Tissue Eng Regen Med. 2026 Jul;23(5):753-770. doi: 10.1007/s13770-026-00809-1.
Xinping Lu  1  2 ,  Huidan Deng  1 ,  Ruotong Mai  3  4 ,  Jingyi Kang  1 ,  Quanjie Li  1 ,  Huijia Li  1 ,  Tingting Liang  1 ,  Qiuxue Chen  1 ,  Yu Wu  5  6
Affiliations
  • 1. National Clinical Medical Research Center for Oral Diseases, Guangxi Branch, Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, Guangxi Clinical Research Center for Craniofacial Deformity, Nanning, 530021, China.
  • 2. College & Hospital of Stomatology, Guangxi Medical University, Nanning, 530021, China.
  • 3. State Key Laboratory of Oral Diseases & National Center for Stomatology &, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
  • 4. Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
  • 5. National Clinical Medical Research Center for Oral Diseases, Guangxi Branch, Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, Guangxi Clinical Research Center for Craniofacial Deformity, Nanning, 530021, China. [email protected].
  • 6. College & Hospital of Stomatology, Guangxi Medical University, Nanning, 530021, China. [email protected].
PMID: 42068522 DOI: 10.1007/s13770-026-00809-1
Abstract

Background: This study evaluated the biocompatibility of small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (hUCMSC) loaded in gelatin methacryloyl hydrogel microspheres (sEVs@GM-MS), and examined their effects on the proliferation and migration of human dental pulp stem cells (hDPSCs)/human umbilical vein endothelial cells (HUVECs), as well as their capacity to promote endothelial cell tube formation. Pulpotomy in a rat molar model was used to assess sEVs@GM-MS as a potential pulp-capping agent.

Methods: sEVs@GM-MS were prepared and physicochemically characterized. In vitro assessments included live/dead staining, Cell Counting Kit-8 (CCK-8), migration assay and tube formation assay. In vivo, 7 and 14 days after pulpotomized with sEVs@GM-MS, GM-MS, iroot BP or without any pulp capping material, rat molars were evaluated using hematoxylin and eosin (H&E), Masson's trichrome, and immunohistochemical (IHC) staining.

Results: GM-MS exhibited a porous surface via scanning electron microscopy. PKH67-labeled sEVs@GM-MS showed sustained release of sEVs. The cell proliferation, migration, tube formation in the sEVs@GM-MS group were significantly enhanced compared with those of the NC and GM-MS groups (p < 0.05). In rat pulpotomy model, sEVs@GM-MS group exhibited significant cell proliferation, angiogenesis, and reparative dentinogenesis with immunocytochemical localization of PCNA, CD31 and DMP-1 compared to NC and GM-MS groups (p < 0.05). Compared with the BP group, the sEVs@GM-MS group showed no significant difference in DMP-1 positive expression (p > 0.05).

Conclusion: sEVs@GM-MS demonstrated excellent biocompatibility, sustained hUCMSC-sEV release, and enhanced pulp/dentin repair and regenaration, highlighting their potential as a pulp-capping agent.

Keywords
Dental pulp stem cells; GelMA; Microspheres; Pulpotomy; hUCMSC; sEVs.
Products