Enhanced osteogenesis of gelatin-halloysite nanocomposite scaffold mediated by loading strontium ranelate

Gelatin-halloysite nanotubes (HNTs) nanocomposite scaffold capable of sustaining the SrR release were introduced for the first time by overcoming the limitations of SrR oral and systemic administration, and also enhancing the physicomechanical, osteogenic potential, and bone forming ability of gelatin-based scaffolds. The mean pore size, porosity, and water absorption, and mechanical properties of gelatin scaffolds increased by adding HNTs, especially after SrR incorporation. As revealed by X-ray diffraction analysis, the layer spaces in HNTs crystals remain unchanged after incorporation in gelatin. Moreover, SrR interacts at the molecular level with HNTs during the scaffold processing. The release profile in the in vitro conditions indicated the control of SrR release by Fickian diffusion and continuation within 21 days. Mesenchymal stem cells (MSCs) on the scaffolds showed that SrR effectively improved proliferation of the MSCs and accelerated osteogenic differentiation as revealed by Alizarin red staining and Real Time Quantitative Reverse transcription polymerase chain reaction (qRT-PCR). In vivo studies demonstrated that the SrR releasing from the Gel/HNTs scaffolds enhanced bone formation and vascularization. Our results suggest that HNTs could control the releasing of SrR and its localized delivery at the defect site, simultaneously with enhancing physicomechanical and bone regeneration ability of gelatin scaffolds.