BMTBiomaterials TranslationalTBA2096-112XBiomaterials Translational10.12336/biomatertransl.2024.01.007Research ArticleMeticulously engineered three-dimensional-printed scaffold with microarchitecture and controlled peptide release for enhanced bone regenerationhttps://artdesignp.com/journal/BMT/5/1/10.12336/biomatertransl.2024.01.007YangJin,FatimaKanwal,ZhouXiaojun,HeChuanglong2024512024-03-28The repair of large load-bearing bone defects requires superior mechanical strength,  a feat that a single hydrogel scaffold cannot achieve. The objective is to seamlessly  integrate optimal microarchitecture, mechanical robustness, vascularisation, and  osteoinductive biological responses to effectively address these critical load-bearing  bone defects. To confront this challenge, three-dimensional (3D) printing technology  was employed to prepare a polycaprolactone (PCL)-based integrated scaffold. Within  the voids of 3D printed PCL scaffold, a methacrylate gelatin (GelMA)/methacrylated  silk fibroin (SFMA) composite hydrogel incorporated with parathyroid hormone  (PTH) peptide-loaded mesoporous silica nanoparticles (PTH@MSNs) was embedded,  evolving into a porous PTH@MSNs/GelMA/SFMA/PCL (PM@GS/PCL) scaffold.  The feasibility of fabricating this functional scaffold with a customised hierarchical  structure was confirmed through meticulous chemical and physical characterisation.  Compression testing unveiled an impressive strength of 17.81 ± 0.83 MPa for the  composite scaffold. Additionally, in vitro angiogenesis potential of PM@GS/PCL  scaffold was evaluated through Transwell and tube formation assays using human  umbilical vein endothelium, revealing the superior cell migration and tube network  formation. The alizarin red and alkaline phosphatase staining assays using bone  marrow-derived mesenchymal stem cells clearly illustrated robust osteogenic  differentiation properties within this scaffold. Furthermore, the bone repair potential  of the scaffold was investigated on a rat femoral defect model using micro-computed  tomography and histological examination, demonstrating enhanced osteogenic and  angiogenic performance. This study presents a promising strategy for fabricating a  microenvironment-matched composite scaffold for bone tissue engineering, providing  a potential solution for effective bone defect repair.angiogenesis; bone regeneration; methacrylated gelatin; methacrylated silk fibroin; osteogenesis; PTH

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