3D-printed conductive hydrogel scaffolds for bone regeneration: Electromechanical coupling, neurovascular integration, and immunomodulatory strategies

Sep 16, 2025Biomaterials advances

3D-printed conductive hydrogel scaffolds for bone healing: electrical and mechanical effects, nerve and blood vessel growth, and immune response control

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

3D-printed conductive hydrogel scaffolds could enhance bone regeneration while supporting nerve repair and blood vessel formation.

These scaffolds combine electrical conductivity with properties similar to the natural extracellular matrix, potentially improving tissue repair.
They promote bone formation by activating signaling pathways that increase osteogenic factors, which are essential for bone growth.
The scaffolds guide nerve cell development and support axon growth, aiding in nerve repair through their conductive and textured surfaces.
Embedded conductive networks within the scaffolds can stimulate the release of factors that encourage new blood vessel formation.
They may influence the immune response by encouraging a healing-promoting macrophage type, helping to create a better environment for recovery.
Current challenges include ensuring long-term compatibility, maintaining bioactivity during fabrication, and optimizing stimulation techniques.

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Bone defect repair remains a formidable clinical challenge due to the limitations of traditional grafts and scaffolds, such as insufficient mechanical compatibility, minimal bioactivity, and poor biomimicry of bone's complex architecture. Emerging 3D-printed conductive hydrogel scaffolds offer a promising solution by combining the electroactive functionality of conductive materials with the cell-friendly, extracellular matrix-like properties of hydrogels. When fabricated into specific architectures via advanced 3D printing techniques, these composite scaffolds provide active biochemical and biophysical cues that enhance tissue regeneration. They can promote osteogenesis by activating key signaling pathways such as integrin-FAK-ERK and Piezo1/2-mediated calcium influx that upregulates osteogenic transcription factors. Simultaneously, they support neurogenesis and angiogenesis: the scaffold's conductivity and micro-topography guide neural differentiation and axon growth for nerve repair, while electrical stimulation and embedded conductive networks trigger the release of angiogenic factors to foster vascular network formation. These scaffolds also modulate the immune response, for example by polarizing macrophages toward a pro-regenerative M2 phenotype, thereby creating a more favorable healing microenvironment. As a result, 3D-printed conductive hydrogels can orchestrate bone regeneration in concert with vascularization and innervation, transcending the single-functionality of conventional scaffolds. Remaining challenges include ensuring long-term biocompatibility, achieving high-resolution microfabrication without compromising bioactivity, and optimizing electrical stimulation parameters for maximal regenerative benefit. Ongoing research is focused on developing bio-safe conductive composites, refining 3D printing methods, and employing dynamic stimulation strategies to address these challenges and accelerate the translation of conductive hydrogel scaffolds into clinical use.

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3D-printed conductive hydrogel scaffolds for bone regeneration: Electromechanical coupling, neurovascular integration, and immunomodulatory strategies

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