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Our results suggested an ideal scaffold with a 0.3 mm pore size and 60% porosity, enabling MG63 cell proliferation and osteogenesis. HSPGs help modulate FGF signaling during MG63 cell differentiation, motivating further studies on the microenvironment involved in neo-bone formation. We used 3D-printed PLA scaffolds coated with HSPG2 to create an osteoconductive environment. Advanced quantitative tests, computed tomography, and confocal microscopy confirmed the efficacy of the scaffold in reducing cranial bone-gap distances. Customized PLA scaffolds repaired diverse bone defects and regulated FGF delivery via HSPG2\/FGF signaling, consequently promoting cranial bone regeneration. 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