- Babaniamansour, Parto; Jacho, Diego; Teow, Ashley; Rabino, Agustin; Garcia-Mata, Rafael; Yildirim-Ayan, Eda
- Mechano-rehabilitation, also known as mechanotherapy, represents the forefront of noninvasive treatment for musculoskeletal tissue (MSK) disorders, encompassing conditions affecting tendons, cartilage, ligaments, and muscles. Recent emphasis has underscored the significance of macrophage presence in the healing of MSK tissues. However, a considerable gap still exists in comprehending how mechanical strains associated with mechanotherapy impact both the naïve and pro-inflammatory macrophage phenotypes within the 3D tissue matrix, as well as whether the shift in macrophage phenotype is contingent upon the mechanical strains inherent to mechanotherapy. In this study, we delineated alterations in mechanoadaptation and polarization of both naïve and M1 macrophages within 3D matrices, elucidating their response to varying degrees of mechanical strain exposure (3%, 6%, and 12%). To evaluate macrophage mechanoadaptation and mechanosensitivity within 3D collagen matrices under mechanical loading, we employed structural techniques (SEM, histology), quantitative morphological measures for phenotypic assessment, and genotypic methods such as quantitative real-time PCR (qRT-PCR). Our data reveal that the response of macrophages to mechanical loading is not only contingent upon their specific sub-phenotype but also varies with the amplitude of mechanical strain. Notably, while supra-mechanical loading (12% strain) was requisite to induce a phenotypic shift in naïve (M0) macrophages, as little as 3% mechanical strain proved sufficient to prompt phenotypic alterations in pro-inflammatory (M1) macrophages. These findings pave the way for leveraging the macrophage mechanome in customized and targeted applications of mechanical strain within the mechanotherapeutic framework. Considering the prevalence of MSK tissue injuries and their profound societal and economic implications, the development of well-informed and effective clinical mechanotherapy modalities for MSK tissue healing becomes an imperative endeavor.
- Tissue engineering. Part A Journal