In vitro bone growth responds to local mechanical strain in three-dimensional polymer scaffolds.

Abstract

Mechanical stimulation plays a key role in healing and remodelling of bone tissue in vivo, and is used in bone tissue regeneration strategies in vitro. Although macroscopic compression of three-dimensional (3-D) seeded constructs can increase bone formation, it is not yet reported how this response is related to differences in local mechanical strains inside the scaffolds. In this study, we experimentally test the hypothesis that differences in local average of heterogeneous strains in a polymer scaffold will correlate with induced differences in the local biological response. Twenty-four poly(L-lactic acid) porous scaffolds seeded with rat bone cells were cultured first for 2 and 3 weeks under static conditions, respectively. Then for 1 week, half of the scaffolds were cyclically compressed (1.5%, 1 Hz), 1 h daily, with continuous perfusion (0.1 ml/min). The remaining half was kept under static conditions. The pore-surface strains in the scaffolds at the start of culture were calculated with micro-finite element modelling based on micro-Computed Tomography (microCT) images. The locations of mineralized nodules were determined from microCT images and coupled to the calculated strains. Detectable mineralized nodules (>10(3) microm3) were only present in the loaded samples. Averages of absolute principal strains at the start of culture were significantly higher at nodule sites than at sites without a nodule. The results support the hypothesis that regenerating bone tissue in a 3-D porous scaffold responds to local mechanical strain. The methodology presented in this study can contribute design optimisation of tissue regeneration strategies relying on mechanical stimulation.