3D‐Printed Biomimetic Vascular Scaffold Crosslinked with Heparan Sulfate for Sustained Release of PDGFB‐LG4 Fusion Protein Promotes Bone Regeneration

Abstract A central focus of bone tissue engineering is the construction of vascular systems, which provide nutrients for cell survival, remove metabolic waste, and accelerate tissue regeneration. Platelet‐derived growth factor‐BB (PDGFB) has the ability to stimulate both vascularization and bone regeneration; however, its clinical application has been hindered by side effects and low efficacy due to suboptimal delivery systems. In this study, a biomimetic vascular scaffold crosslinked with heparan sulfate (HS) is developed to enable sustained delivery of the PDGFB‐LG4 fusion protein, targeting the regeneration of critically sized bone defects. The scaffold is designed with a vascular‐like hierarchical structure, incorporating a customized 3D framework, multibranched microchannels, and permeable porous walls, which facilitates mass exchange and cell infiltration. PDGFB‐LG4 exhibits superior osteoinductive and angiogenic activity compared to PDGFB. In a calvarial defect model, the composite scaffold (PCLHS‐PDGFB‐LG4) significantly enhances both vascularization and bone regeneration, demonstrating improved efficacy at lower doses compared to PDGFB. This approach may be applicable to other growth factors and gelatin‐based materials, offering the potential for a wide range of applications in regenerative medicine.