Enhancing the efficiency of bone tissue regeneration by using a 3D printed scaffold optimized with heparan sulfate proteoglycan 2

Craniofacial bone deficiencies caused by trauma or disease pose clinical challenges as the shape of the damaged area varies between people. Although bone grafts are effective, they face issues such as poor drug retention and potential immune responses. PLA scaffolds possess therapeutic potential owing to their size, mechanical properties, stability, and biocompatibility. However, PLA scaffolds inherently lack bioactive molecules necessary to promote osteogenesis. HSPG2, also known as perlecan (Pln), are a basement membrane-specific GAG-containing core protein. Pln is a reservoir for heparin-binding growth factors, such as FGF, through GAG chains in domain I. For these reasons, we designed an HSPG2-coated PLA scaffold to enhance FGF delivery and promote cranial bone regeneration. 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. This study demonstrated promising applications for the treatment of cranial bone defects.