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

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.