A Bone Marrow-Mimetic Hydrogel Enables Dual-Phase Hemostasis and Vascularized Osteogenesis for Cranial Defects

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Critical-sized cranial defects pose challenges in hemostasis and bone regeneration.
• Existing implants inadequately address these sequential demands.
• Native bone marrow's complex microenvironment is key for healing.

Purpose of the Study:

• To engineer a bone marrow-mimetic composite hydrogel (FE-PDA@Fib/Gel-TG) for cranial defect repair.
• To achieve immediate hemostasis and long-term vascularized bone regeneration.
• To recapitulate bone marrow's biochemical and biomechanical properties.

Main Methods:

• Fabrication of a composite hydrogel integrating gelatin, polydopamine-coated hydroxyapatite/poly(L-lactic acid) fibers, and fat extract.
• Assessment of hemostatic properties via mechanical sealing and catechol-assisted clot stabilization.
• Evaluation of pro-regenerative effects, cell recruitment, osteogenesis, and angiogenesis in vitro and in vivo.
• Transcriptomic analysis to elucidate underlying signaling pathways (VEGF/VEGFR-PI3K-AKT).
• In vivo testing in a critical-sized calvarial defect model.

Main Results:

• The hydrogel achieved immediate hemostasis and promoted a pro-regenerative microenvironment.
• Enhanced cell recruitment, endothelial network formation, and osteogenic differentiation were observed.
• Successful vascular-bone coupling was driven by VEGF/VEGFR-PI3K-AKT signaling.
• The hydrogel steered macrophage polarization toward an anti-inflammatory phenotype.
• Robust regeneration of mature, vascularized bone tissue in calvarial defects.

Conclusions:

• The FE-PDA@Fib/Gel-TG hydrogel effectively mimics bone marrow for cranial defect repair.
• It successfully couples rapid hemostasis with programmed osteo-angiogenesis.
• This multifunctional biomimetic platform offers a translatable solution for cranial defect regeneration.