Functionalized hydrogel-microsphere composites stimulating neurite outgrowth for vascularized bone regeneration

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Neurovascularized bone regeneration is a significant clinical challenge.
• Biomaterials that mimic developmental microenvironments can enhance tissue regeneration.
• Current strategies often fail to adequately address the complex interplay of nerves, blood vessels, and bone tissue.

Purpose of the Study:

• To develop functionalized hydrogel-microsphere composites to create a neurovascularized microenvironment for enhanced bone regeneration.
• To investigate the role of specific peptides and nanoparticles in promoting cell proliferation, differentiation, and recruitment.
• To evaluate the efficacy of the composite in promoting bone formation, nerve infiltration, and angiogenesis in vivo.

Main Methods:

• Fabrication of hydrogel-microsphere composites functionalized with RGD, BFP-1, QK, and IK19 peptides, and mesoporous silica nanoparticles (MSNs).
• In vitro assessment of human mesenchymal stem cell (hMSC) proliferation, migration, and osteogenic differentiation.
• In vitro assessment of endothelial cell (EC) recruitment and neurite outgrowth.
• In vivo evaluation of bone regeneration, nerve infiltration, and angiogenesis in a bone defect model.

Main Results:

• The composite promoted hMSC proliferation and migration via RGD peptide and porous structure.
• MSNs delivered BFP-1 peptide, enhancing hMSC osteogenic differentiation.
• QK peptide recruited endogenous ECs, and IK19 peptide guided neurite outgrowth.
• In vivo studies demonstrated enhanced new bone formation, nerve infiltration, and angiogenesis.
• The created neurovascularized niche stimulated neurite growth via MAPK, PI3K, IL17, and TNF signaling pathways.

Conclusions:

• The developed hydrogel-microsphere composite effectively creates a neurovascularized microenvironment for bone regeneration.
• This bioengineering approach facilitates functional bone repair by promoting bone formation, vascularization, and nerve regeneration.
• The findings offer a promising strategy for developing advanced bone graft materials for clinical applications.