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

Abstract

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.

Graphical Abstract

Keywords:

• Gelatin
• halloysite
• in vivo
• nanocomposite
• osteogenesis
• strontium ranelate

Acknowledgments

The authors appreciate Alexandra de Francisco, Yolanda Sierra, and María de la Jara Felipe for technical assisting.

Additional information

Funding

This work was partially funded by University of Tehran for PhD grant [No. 30109/06/16], Institute of ceramic and glass ((ICV-CSIC), Madrid, Spain), and the Community of Madrid (S2017/BMD-3867 RENIM-CM) and co-financed with Structural Funds of the European Union and Comunidad de Madrid (ADITIMAT: S2018/NMT-4411, and MERA.NET PCIN-2017-036 (MINECO, Spain). The CNIC was funded by the Ministry of Science, Innovation and Universities and the Pro CNIC Foundation, and was a Severo Ochoa Center of Excellence (SEV-2015-0505).