The Intersection of Mechanotransduction and Regenerative Osteogenic Materials

Mechanical signals play a central role in cell fate determination and differentiation in both physiologic and pathologic circumstances. Such signals may be delivered using materials to generate discrete microenvironments for the purposes of tissue regeneration and have garnered increasing attention in recent years. Unlike the addition of progenitor cells or growth factors, delivery of a microenvironment is particularly attractive in that it may reduce the known untoward consequences of the former two strategies, such as excessive proliferation and potential malignant transformation. Additionally, the ability to spatially modulate the fabrication of materials allows for the creation of multiple microenvironments, particularly attractive for regenerating complex tissues. While many regenerative materials have been developed and tested for augmentation of specific cellular responses, the intersection between cell biology and material interactions have been difficult to dissect due to the complexity of both physical and chemical interactions. Specifically, modulating materials to target individual signaling pathways is an avenue of interdisciplinary research that may lead to a more effective method of optimizing regenerative materials. In this work, the aim is to summarize the major mechanotransduction pathways for osteogenic differentiation and to consolidate the known materials and material properties that activate such pathways. One of the frontiers in the development of regenerative materials is the interdisciplinary efforts in understanding how specific alterations in material properties may effect intracellular signaling pathways and cellular responses. This review summarizes the major mechanotransduction pathways, the intersection between mechanotransduction and osteogenic signaling, and consolidates the known skeletal regenerative materials and material properties that activate such cascades.