A bilayer hydrogel mimicking the periosteum-bone structure for innervated bone regeneration

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Nerves in the periosteum are crucial for bone defect repair, yet current bone tissue engineering often neglects nerve network reconstruction.
• Developing biomaterials that support both neurogenesis and osteogenesis is essential for effective bone regeneration.

Purpose of the Study:

• To create a bilayer hydrogel system simulating periosteum-bone structure to induce innervated bone regeneration.
• To investigate the role of controlled magnesium ion release and nano-hydroxyapatite incorporation in promoting nerve and bone healing.

Main Methods:

• Fabrication of a bilayer hydrogel: a 'bone' layer (GelMA/PEGDA/nHA) and a 'periosteum' layer (GelMA/SA/MgCl2).
• Tuning mechanical properties for specific cellular responses (neurogenesis and osteogenesis).
• In vitro studies using rat dorsal root ganglion (DRG) neurons and bone-derived mesenchymal stem cells (BMSCs).
• In vivo evaluation in rat calvarial bone defect models.

Main Results:

• The bilayer hydrogel (GS@Mg/GP@nHA) successfully promoted neurite outgrowth and calcitonin gene-related peptide (CGRP) expression in DRG neurons.
• Enhanced osteogenesis of BMSCs was observed.
• In vivo studies demonstrated efficient nerve network reconstruction and significant bone regeneration in calvarial defects.

Conclusions:

• The developed bilayer hydrogel effectively promotes innervated bone regeneration by supporting both nerve and bone healing.
• This biomaterial design offers a novel strategy for bone tissue engineering, addressing the critical need for nerve integration.
• Controlled release of magnesium ions and incorporation of nano-hydroxyapatite are key factors in achieving synergistic regenerative outcomes.