IL-4/Nanohydroxyapatite Codelivery in a Dual-Bionic Scaffold: Design and Immunomodulatory Endogenous Osteogenesis...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Bone defect repair is limited by extracellular matrix (ECM) signaling deficiency and poor biomimicry.
• Current 3D-printed polycaprolactone/nanohydroxyapatite (PCL/nHA) scaffolds lack sufficient bioactivity and osteogenic capacity.

Purpose of the Study:

• To design a dual-bionic PCL/nHA scaffold combining "soft" ECM signaling mimicry with "hard" structural support.
• To enhance endogenous bone regeneration by addressing limitations in current bone defect repair strategies.

Main Methods:

• Developed a PCL/nHA scaffold with a gyroid architecture and integrated hydrogel for controlled interleukin-4 (IL-4) release.
• Investigated the scaffold's ability to induce macrophage M2 polarization and subsequent anti-inflammatory cytokine secretion (IL-10, TGF-β).
• Analyzed the role of sustained nanohydroxyapatite (nHA) hydrolysis and Ca2+ release in activating PI3K-AKT and calcium signaling pathways.

Main Results:

• The scaffold successfully mimicked ECM signaling, enabling time-programmed IL-4 release to promote M2 macrophage polarization.
• IL-4 release led to increased secretion of IL-10 and TGF-β, initiating osteogenesis.
• Sustained nHA hydrolysis released Ca2+, which synergized with cytokines to activate signaling pathways, upregulating osteogenic and angiogenic markers.

Conclusions:

• Demonstrated a coupling mechanism between immunomodulation and osteogenic differentiation for enhanced bone regeneration.
• The dual-bionic scaffold presents a novel strategy for promoting endogenous bone repair by mimicking natural bone microenvironments.
• This approach overcomes limitations of current scaffolds by integrating bioactive signaling with structural biomimicry.