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Peer-reviewedCC BY 4.0Biomolecules

Periodontal Regeneration Using a Mineralizing Hydrogel Loaded with a Synthetic CEMP1-Derived Peptide

  • Yu Wang1
  • Guangzhao Guan2
  • Li Mei3
  • Huiwen Zheng1
  • Xianghui Xing1
  • Weibin Sun4
4 affiliations
  1. 1Department of Pediatric Dentistry, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing 210008, China
  2. 2Department of Oral Diagnostic and Surgical Sciences, Faculty of Dentistry, University of Otago, Dunedin 9016, New Zealand
  3. 3Department of Oral Sciences, Faculty of Dentistry, University of Otago, Dunedin 9016, New Zealand
  4. 4Department of Periodontology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing 210008, China
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Abstract

Background: Periodontal regeneration requires the coordinated reconstruction of mineralized and non-mineralized tissues. P35 polypeptide derived from Cementum protein-1(CEMP1) has been demonstrated to induce bio-mineralization in vitro, although in vivo applications still need to be further validated. In this study, we developed a novel mineralizing hydrogel system (P35/ACP@PEG Hy) to facilitate periodontal regeneration by encapsulating P35-loaded amorphous calcium phosphate nanoparticles (P35/ACP-NPs) within a four-arm polyethylene glycol (PEG) hydrogel. Methods: In vitro assays were performed to characterize the physicochemical properties, sustained-release behavior, osteogenic/cementogenic effects of P35/ACP-NPs on hPDLCs, together with the mechanical performance and biocompatibility of the PEG hydrogel. The regenerative capacity of the hydrogel was further assessed in a rat periodontal defect model using micro-CT and histological staining. The regenerative efficacy was evaluated in a rat periodontal defect model via micro-CT and histological staining, while transcriptome sequencing (RNA-seq) and immune-blotting were further performed to confirm the molecular mechanisms. Results: P35/ACP@PEG exhibited favorable physicochemical properties, featuring an initial burst release followed by a sustained gradual release profile, along with the excellent biocompatibility. In vitro, P35/ACP-NPs markedly promoted osteogenic and cementogenic differentiation of hPDLCs. Correspondingly, the P35/ACP@PEG hydrogel significantly accelerated periodontal tissue regeneration in the rat model with periodontal defect. And RNA-seq analysis and immune-blotting further revealed that these effects are highly linked to activation of the TGF-β/Smad2/3/LOX signaling pathway. Conclusions: P35/ACP@PEG Hy platform can promote periodontal regeneration via activation of TGF-β/Smad2/3/LOX signaling pathway in vivo. Its sustained bioactivity, favorable biocompatibility and robust regenerative efficacy highlight a potential of P35 polypeptide for periodontal tissue repair.

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Cite

BibTeXRIS
BibTeX
@article{wang2026periodontal,
  title = {{Periodontal Regeneration Using a Mineralizing Hydrogel Loaded with a Synthetic CEMP1-Derived Peptide}},
  author = {Yu Wang and Guangzhao Guan and Li Mei and Huiwen Zheng and Xianghui Xing and Weibin Sun},
  journal = {Biomolecules},
  year = {2026},
  month = oct,
  doi = {10.3390/biom16101444},
  url = {https://www.mdpi.com/2218-273X/16/10/1444},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Periodontal Regeneration Using a Mineralizing Hydrogel Loaded with a Synthetic CEMP1-Derived Peptide
AU  - Yu Wang
AU  - Guangzhao Guan
AU  - Li Mei
AU  - Huiwen Zheng
AU  - Xianghui Xing
AU  - Weibin Sun
PY  - 2026
DA  - 2026/10/01
JO  - Biomolecules
DO  - 10.3390/biom16101444
UR  - https://www.mdpi.com/2218-273X/16/10/1444
AB  - Background: Periodontal regeneration requires the coordinated reconstruction of mineralized and non-mineralized tissues. P35 polypeptide derived from Cementum protein-1(CEMP1) has been demonstrated to induce bio-mineralization in vitro, although in vivo applications still need to be further validated. In this study, we developed a novel mineralizing hydrogel system (P35/ACP@PEG Hy) to facilitate periodontal regeneration by encapsulating P35-loaded amorphous calcium phosphate nanoparticles (P35/ACP-NPs) within a four-arm polyethylene glycol (PEG) hydrogel. Methods: In vitro assays were performed to characterize the physicochemical properties, sustained-release behavior, osteogenic/cementogenic effects of P35/ACP-NPs on hPDLCs, together with the mechanical performance and biocompatibility of the PEG hydrogel. The regenerative capacity of the hydrogel was further assessed in a rat periodontal defect model using micro-CT and histological staining. The regenerative efficacy was evaluated in a rat periodontal defect model via micro-CT and histological staining, while transcriptome sequencing (RNA-seq) and immune-blotting were further performed to confirm the molecular mechanisms. Results: P35/ACP@PEG exhibited favorable physicochemical properties, featuring an initial burst release followed by a sustained gradual release profile, along with the excellent biocompatibility. In vitro, P35/ACP-NPs markedly promoted osteogenic and cementogenic differentiation of hPDLCs. Correspondingly, the P35/ACP@PEG hydrogel significantly accelerated periodontal tissue regeneration in the rat model with periodontal defect. And RNA-seq analysis and immune-blotting further revealed that these effects are highly linked to activation of the TGF-β/Smad2/3/LOX signaling pathway. Conclusions: P35/ACP@PEG Hy platform can promote periodontal regeneration via activation of TGF-β/Smad2/3/LOX signaling pathway in vivo. Its sustained bioactivity, favorable biocompatibility and robust regenerative efficacy highlight a potential of P35 polypeptide for periodontal tissue repair.
SN  - 2218-273X
ER  -