Porous aligned ZnSr-doped β-TCP/silk fibroin scaffolds using ice-templating method for bone tissue engineering applications

Abstract

The bone is a complex and dynamic structure subjected to constant stress and remodeling. Due to the worldwide incidence of bone disorders, tissue scaffolds and engineered bone tissues have emerged as solutions for bone grafting, which require sophisticated scaffolding architectures while keeping high mechanical performance. However, the conjugation of a bone-like scaffold architecture with efficient mechanical properties is still a critical challenge for biomedical applications. In this sense, the present study focused on the modulating the architecture of silk fibroin (SF) scaffolds crosslinked with horseradish peroxidase and mixed with zinc (Zn) and strontium (Sr)-doped β-tricalcium phosphate (ZnSr.TCP) to mimic bone structures. The ZnSr.TCP-SF hydrogels were tuned by programmable ice-templating parameters, and further freeze-dried, in order to obtain 3D scaffolds with controlled pore orientation. The results showed interconnected channels in the ZnSr.TCP-SF scaffolds that mimic the porous network of the native subchondral bone matrix. The architecture of the scaffolds was characterized by microCT, showing tunable pore size according to freezing temperatures (−196 °C: ∼80.2 ± 20.5 µm; −80 °C: ∼73.1 ± 20.5 µm; −20 °C: ∼104.7 ± 33.7 µm). The swelling ratio, weight loss, and rheological properties were also assessed, revealing efficient scaffold integrity and morphology after aqueous immersion. Thus, the ZnSr.TCP-SF scaffolds made of aligned porous structure were developed as affordable candidates for future applications in clinical osteoregeneration and in vitro bone tissue modelling.

Graphical abstract

Keywords:

• ZnSr-doped β-tricalcium phosphate
• silk fibroin
• ice-templating
• pore alignment
• scaffolds
• bone tissue engineering

Acknowledgements

The authors acknowledge FCT for the financial support of the Hierarchitech project (M-ERA.NET/0001/2014) and for the distinctions attributed to S.P. (CEECIND/03673/2017) and C. G. (SFRH/BPD/94277/2013). R. F. Canadas is also thankful to FCT for the doctoral scholarship (SFRH/BD/92565/2013), Fundo Europeu de Desenvolvimento Regional (FEDER), and Programa Operacional Competitividade e Internacionalização (POCI) for funding the Young Researcher Contract (B-Liver Project, PTDC/EMD-EMD/29139/2017).