Scaffold-guided bone defect regeneration: Effect of chronological ageing

• Applicant: Su Ping Patrina Poh, Ph.D.
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 435204959

Ageing is associated with impaired endogenous bone healing capacity, which substantially increased the challenge for the regeneration of large bone defect. Recently, the general possibility of using cell- and growth factor-free scaffolds with optimised mechanobiological properties and architecture, respectively, as a guiding frame to support endogenous bone regeneration have been demonstrated by our group in young animals. Nevertheless, the understanding of how chronological ageing affects the underlying biological mechanisms of the scaffold-aided bone defect regeneration is widely missing. A more mechanistic understanding of the age-associated alterations in bone regeneration in relation to the scaffolds’ mechanobiological and architecture is crucial for the development of an age-matched structure to enhance bone defect regeneration even in advanced ages. The objective of this project is to systematically evaluate the underlying age-related mechanistic differences in scaffold-aided bone defect regeneration in relation to the mechanobiological principle and scaffolds’ architecture. This project will leverage on additive manufacturing (AM) technology for the realisation of biodegradable scaffolds with controlled mechanobiological properties and architecture. Firstly, in vivo study will be performed to deduce if the mechanobiological principle of scaffold-guided bone regeneration holds true in a chronologically aged individual, which is known to have compromised sensitivity to mechanical stimuli. Subsequently, proof-of-concept in vitro and in vivo study will be performed to investigate the possibility of enhancing bone defect regeneration in the aged individual by coupling of mechanobiological principles and guided tissue formation by modulating scaffolds’ architecture. The mechanistic differences in scaffold-aided bone defect regeneration between young and aged will be compared at the gene (by RT-qPCR), protein (by multiplex ELISA array) and morphological (by µCT, histology) levels. Such understanding is crucial from both a basic mechanistic understanding as well as from a translational perspective to guide the development of optimized AM scaffolds to support endogenous bone regeneration. Ultimately, such a mechanistic understanding would shift the trial-and-error paradigm towards data-driven additive design, engineering and manufacturing of personalised scaffolds intended for bone regeneration.

• DFG Programme: Research Grants