MgAl layered double hydroxide/chitosan porous scaffolds loaded with PFTα to promote bone regeneration

Poor bone formation remains a key risk factor associated with acellular scaffolds that occurs in some bone defects, particularly in patients with metabolic bone disorders and local osteoporosis. We herein fabricated for the first time layered double hydroxide-chitosan porous scaffolds loaded with PFTα (LDH-CS-PFTα scaffolds) as therapeutic bone scaffolds for the controlled release of PFTα to enhance stem cell osteogenic differentiation and bone regeneration. The LDH-CS scaffolds had three-dimensional interconnected macropores, and plate-like LDH nanoparticles were uniformly dispersed within or on the CS films. The LDH-CS scaffolds exhibited appropriate PFTα drug delivery due to hydrogen bonding among LDH, CS and PFTα. In vitro functional studies demonstrated that the PFTα molecules exhibited potent ability to induce osteogenesis of hBMSCs via the GSK3β/β-catenin pathway, and the LDH-CS-PFTα scaffolds significantly enhanced the osteogenic differentiation of hBMSCs. In vivo studies revealed significantly increased repair and regeneration of bone tissue in cranial defect model rats compared to control rats at 12 weeks post-implantation. In conclusion, the LDH-CS-PFTα scaffolds exhibited excellent osteogenic differentiation and bone regeneration capability and hold great potential for applications in defined local bone regeneration.