Wnt-activated osteocyte-driven 3D-bioprinted scaffolds orchestrate bone remodeling, angiogenesis, and innervation to accelerate critical bone defect repair
Year: 2026
Type: article
Abstract: Effective repair of critical bone defects necessitates biomaterials that simultaneously couple bone remodelling (osteogenesis-osteoclastogenesis) with neurovascularisation. However, existing multifunctional systems face bottlenecks, including co-culture instability and unpredictable release, due to their reliance on multiple cell types or growth factors. To address this, we developed a 3D-bioprinted scaffold by co-encapsulating SKL2001 (S24)-treated osteocyte osteogenic microenvironment (SOOME) and BMSCs in a GelMA hydrogel within a polycaprolactone (PCL) framework, which is referred to as the SOOME/BMSC@PCL scaffold. In a murine critical-sized calvarial defect model, the SOOME achieved 52.3% bone area fill at 8 weeks, a 5.1-fold increase over the BMSC-only control. It also significantly stimulated osteoclast recruitment, accompanied by elevated bone formation, induced abundant H-type vascularisation, and promoted neural infiltration. Transcriptomic analysis identified Vgf as a differentially expressed gene that partially contributed to the multifunctional integration of SOOME. This research establishes a simpler and more controllable strategy for synergistic regulation of osteogenic, osteoclastic, vascular, and neural functions within a SOOME-centered material system, providing new insights into the functional selection of seed cells and opening avenues for clinical translation of bioactive bone grafts.
Source: Regenerative Biomaterials
DOI: 10.1093/rb/rbag124
Authors: Yangxi Liu, Jian Huang, Shan Li, Xiaolin Tu
Institution: Chongqing Medical University
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $1,820
OpenAlex ID: W7164887478
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