Zaotang-inspired pull-folding approach to fabricate oriented multifunctional scaffolds for bone repair

Bone defects caused by trauma, tumors, or infections impose significant clinical challenges due to donor scarcity and complications in traditional grafting. Current scaffold fabrication techniques like electrospinning and 3D printing face limitations in mechanical strength, process complexity, and production costs. Herein, we developed a cost-effective, solvent-free fabrication method inspired by traditional Chinese "Zaotang" candy-pulling techniques. By blending polycaprolactone (PCL) and collagen under controlled heating, a malleable composite was formed, which then mimicked Zaotang's honeycomb-forming process, repetitive pulling and folding of the semi-solid mixture induced structural orientation and porosity without solvents or specialized equipment. Subsequent in situ mineralization with strontium-apatite (SrAP) further augments bioactivity, leveraging Sr²⁺ ions' dual role in angiogenesis and osteogenesis. Systematic characterization confirmed the SrAP mineralization homogeneity and interfacial stability. In vitro studies demonstrated 1.37-fold enhanced osteoblast migration versus the PCL-collagen scaffold and 1.15-fold/121.26-fold upregulated VEGFA/Runx2 expression, respectively. Rat calvarial defect models revealed 50.85 % bone regeneration at 6 weeks, with micro-CT/histology showing mature vascularized bone formation. This Zaotang-inspired strategy established a scalable paradigm for functional bone scaffolds, merging cultural heritage with regenerative engineering to demonstrate significant translational potential for bone defect reconstruction.