Revitalizing bioinert PCL: A biomimetic 3D-Printed gradient-pore scaffold with CSMA hydrogel-mediated BMP-2/QK delivery for vascularized bone regeneration.

Authors

Zekun Zhang, Chunjiao Huang, Wenbin Hu, Shikun Wu

Published in

Journal of biomaterials applications. Pages 8853282261492945. Sep 29, 2026. Epub Sep 29, 2026.

Abstract

Critical-sized bone defects exceed bone's regenerative capacity and require space-maintaining implants that support vascular and bone-tissue ingrowth. Three-dimensional (3D)-printed polycaprolactone (PCL) scaffolds are widely investigated for bone repair owing to controllable geometry, interconnected macropores, and structural stability. However, uniform-pore designs cannot recapitulate heterogeneous bone porosity, while hydrophobic PCL has limited bioactivity. Inspired by the transition from dense cortical to porous cancellous bone, we designed a stepwise gradient-pore PCL framework combining compact regions for structural support with progressively more open regions, providing multiple cell- and tissue-relevant environments. An in situ photocrosslinked methacrylated chondroitin sulfate (CSMA) hydrogel containing bone morphogenetic protein-2 (BMP-2) and the vascular endothelial growth factor-mimetic QK peptide was formed within the printed pores as a hydrated delivery phase. The scaffold retained sequential dense, intermediate, and loose regions; CSMA improved wettability; and PCL confinement slowed the release of both factors relative to hydrogel alone, with QK reaching approximately 80% cumulative release by day 14 and BMP-2 approximately 65% by day 28. Relative to PCL and PCL-CSMA, PCL-CSMA-QK-BMP enhanced endothelial responses, rat bone marrow mesenchymal stem cell proliferation and migration, and osteogenic differentiation and mineralization. Single-factor comparisons supported QK-related endothelial and BMP-2-related osteogenic effects. In rat calvarial defects, PCL-CSMA-QK-BMP increased bone volume fraction, trabecular number, bone mineral density, collagen-rich matrix deposition, and osteogenic and angiogenesis-associated marker expression at 4 and 8 weeks relative to PCL and PCL-CSMA. These findings support coupling graded macroporosity with a hydrated delivery phase for vascularized bone regeneration.

PMID:
42809636
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

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