Scaffold configuration and micromechanics regulating macrophage-driven biomaterial degradation through mechanosensing

Abstract text (incl. figure legends and references)

Question: Biodegradable synthetic scaffolds present a flexible and auspicious category of biomaterials with high application potential in tissue engineering, such as cardiac function restoration.1 The regeneration of functional tissue in situ highly relies on the equilibrium between scaffold degradation and neo-tissue formation. Macrophages play a crucial role in both these processes. This study mainly aimed to investigate the influence of scaffold configuration and micromechanical properties on mechano-sensation and –transduction in macrophages, as well as the degradation behavior of the scaffold driven by macrophages.

Methods: Polyesteretherurethane (PEEU), which has been proved to promote angiogenesis2, was prepared either as fiber meshes or as bulk films. The degradation behavior was examined by analyzing morphological and mechanical changes using scanning electron microscopy (SEM), tensile testing, and atomic force microscopy (AFM). The cell recruitment, morphology and reactive oxygen species (ROS) production of macrophages were assessed by SEM, confocal microscopy and ELISA.

Results: The promoted oxidative degradation was observed on PEEU mesh with surface elasticity of 1.1 MPa, compared to PEEU film of 187 MPa. As a major trigger of oxidative degradation, ROS was produced to a higher level by macrophages growing on mesh, presenting a 1.5-fold change compared to the film group. Blockage and activation experiment confirmed that ROS secretion and macrophage-driven degradation were mediated by mechano-sensation and –transduction process, including cytoskeleton assembly and Piezo stimulation.

Conclusion: The understanding of the mechanosensing process may guide us for future scaffold development.

Tung, W. T., et al. Adv Funct Mater 2022, 32 (31). Sun, X. L., et al. Clin Hemorheol Micro 2020, 74 (4), 405-415.