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Related Experiment Video

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Mechanically Robust Hydrogels Facilitating Bone Regeneration through Epigenetic Modulation.

Tingting Yu1,2, Lingyun Zhang1,2, Xueyu Dou3,4

  • 1Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|September 26, 2022
PubMed
Summary
This summary is machine-generated.

This study developed a dual crosslinked hydrogel biomaterial that mimics bone extracellular matrix for enhanced bone regeneration. The novel hydrogel promotes stem cell osteogenesis via a Tet2-mediated signaling pathway.

Keywords:
bone tissue engineeringepigenetic regulationhydrogelsmesenchymal stem cellspolyhedral oligomeric silsesquioxane

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Area of Science:

  • Biomaterials Science
  • Tissue Engineering
  • Regenerative Medicine

Background:

  • Bone regeneration strategies often mimic the natural bone extracellular matrix.
  • Hydrogels are promising biomaterials but suffer from weak mechanics and inhomogeneous networks, limiting clinical use.
  • Developing advanced hydrogels with tunable properties is crucial for effective bone tissue engineering.

Purpose of the Study:

  • To develop a dual crosslinked hydrogel system with tunable architecture and mechanics for enhanced bone regeneration.
  • To investigate the osteogenic potential of the developed hydrogel in promoting periodontal ligament stem cell (PDLSC) proliferation, attachment, and differentiation.
  • To elucidate the underlying epigenetic mechanisms, specifically the role of ten-eleven translocation 2 (Tet2), in mediating the hydrogel's osteogenic effects.

Main Methods:

  • Fabrication of a dual crosslinked hydrogel using polyhedral oligomeric silsesquioxane (POSS) cores with disulfide-linked PEG shells and 2-ureido-4[1H]-pyrimidinone (UPy) groups.
  • Utilized thiol-disulfide exchange for pH-responsive chemical network formation and UPy motifs for microstructural enhancement.
  • Evaluated hydrogel biocompatibility, mechanical properties, and in vitro/in vivo osteogenic potential using PDLSCs.
  • Investigated the epigenetic regulation of WNT/β-catenin signaling pathway involving Tet2, HDAC1, and E-cadherin.

Main Results:

  • The developed hybrid hydrogel demonstrated tunable architectures and enhanced mechanical properties.
  • The hydrogel supported PDLSC proliferation, attachment, and significantly promoted osteogenesis both in vitro and in vivo.
  • Identified Tet2 as a key epigenetic regulator that enhances WNT/β-catenin signaling through the Tet2/HDAC1/E-cadherin/β-catenin cascade, thereby promoting PDLSC osteogenesis.

Conclusions:

  • The dual crosslinked hydrogel offers a promising biomaterial for bone regeneration with tunable properties and excellent biocompatibility.
  • This study reveals a novel epigenetic mechanism involving Tet2 in mediating hydrogel-induced osteogenesis.
  • The findings provide a general strategy for designing advanced biomaterials for tissue engineering and offer insights into osteogenic mechanisms.