AUTHOR=Xiao Fei , Shi Jingjing , Zhang Xinhai , Hu Min , Chen Kangming , Shen Chao , Chen Xiaodong , Guo Yaping , Li Yang TITLE=Gadolinium-doped whitlockite/chitosan composite scaffolds with osteogenic activity for bone defect treatment: In vitro and in vivo evaluations JOURNAL=Frontiers in Bioengineering and Biotechnology VOLUME=Volume 11 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2023.1071692 DOI=10.3389/fbioe.2023.1071692 ISSN=2296-4185 ABSTRACT=Reducing the incidence of bone defects caused by trauma and other primary diseases is an urgent task in modern society. In the present study, we developed a gadolinium-doped whitlockite/chitosan (Gd-WH/CS) scaffold and assessed its biocompatibility, osteoinductivity, and bone regeneration capacity for the treatment of calvarial defect in an Sprague-Dawley (SD) rat model. The Gd-WH/CS scaffolds possessed a macroporous structure, with a pore size ranging 200–300 μm, which facilitated the adhesion of cells and growth of bone tissue into the scaffold. In vitro and in vivo results showed that both the WH/CS and Gd-WH/CS scaffolds were non-cytotoxic to human adipose-derived stromal cells (hADSCs) and bone tissue, which demonstrated the excellent biocompatibility of Gd-WH/CS scaffolds. The Gd3+ ions in the Gd-WH/CS scaffolds significantly improved the osteogenic activity via the GSK3β/β-catenin signaling pathway and upregulated the expression of osteogenic-related genes including osteocalcin (OCN), osterix (OSX), and collagen 1A1 (COL1A1). SD rat cranial defect models further demonstrated that Gd-WH/CS scaffolds significantly accelerated bone tissue growth due to its degradation rate and excellent osteogenic activity. This study suggests the potential utility of the Gd-WH/CS hybrid scaffolds in treating bone defect disease.