New Dimension in Senescence: Unraveling Cellular Senescence in Three-Dimensional Scaffolds

Abstract

Aging is a ubiquitous process that results in the progressive and irreversible loss of function. It is induced by accumulating damage caused by a variety of stressors, both internal and external. Although the advancement of modern medicine has enhanced human health and significantly extended life expectancy, with the aging of society, various age-associated chronic diseases have gradually become the primary cause of disability and death. The world’s population of people aged 60 years and older is growing rapidly, meaning people worldwide live longer. Thus, a segment of the population considered an outlier and excluded from drug screening and disease-based studies has now become the primary focus of research. The aging process starts at the cellular level, and cellular senescence is a major contributing factor. Traditionally, cellular senescence has been studied using conventional two-dimensional (2D) cell culture systems, which do not recapitulate the complex three-dimensional (3D) microenvironment of the soft human tissues. On the other hand, animal models suffer from various limitations, such as high cost, ethical concerns, and physiological differences between species. These challenges underscore the need for engineering organotypic models to investigate senescence and screen anti-aging drugs. The work lays the groundwork for developing more complex 3D scaffolds to decipher the aging process by utilizing conventional fabrication methods such as electrospinning and salt leaching with modern state-of-the-art 3D printing. Furthermore, the fabricated model systems can be used as drug-testing platforms for senolytic and senostatic drugs