Metastasis is a dynamic process in which cancer cells navigate the tumor microenvironment, largely guided by external chemical and mechanical cues. Our current understanding of metastatic cell migration has relied primarily on studies of single cell migration, most of which have been performed using two-dimensional (2D) cell culture techniques and, more recently, using three-dimensional (3D) scaffolds. However, the current paradigm focused on single cell movements is shifting toward the idea that collective migration is likely one of the primary modes of migration during metastasis of many solid tumors. Not surprisingly, the mechanics of collective migration differ significantly from single cell movements. As such, techniques must be developed that enable in-depth analysis of collective migration, and those for examining single cell migration should be adopted and modified to study collective migration to allow for accurate comparison of the two. In this review, we will describe engineering approaches for studying metastatic migration, both single cell and collective, and how these approaches have yielded significant insight into the mechanics governing each process.

Developing therapeutic molecules that target chondrocytes and locally produced inflammatory factors within arthritic cartilage is an active area of investigation. The extensive studies that have been conducted over the past 50 years have enabled the accurate prediction and reliable optimization of the transport of a wide variety of molecules into cartilage. In this Review, the factors that can be used to tune the transport kinetics of therapeutics are summarized. Overall, the most crucial factor when designing new therapeutic molecules is solute size. The diffusivity and partition coefficient of a solute both decrease with increasing solute size as indicated by molecular mass or by hydrodynamic radius. Surprisingly, despite having an effective pore size of ~6 nm, molecules of ~16 nm radius can diffuse through the cartilage matrix. Alteration of the shape or charge of a solute and the application of physiological loading to cartilage can be used to predictably improve solute transport kinetics, and this knowledge can be used to improve the development of therapeutic agents for osteoarthritis that target the cartilage.

The human intervertebral disc (IVD) is a complex organ composed of fibrous and cartilaginous connective tissues, and it serves as a boundary between 2 adjacent vertebrae. It provides a limited range of motion in the torso as well as stability during axial compression, rotation, and bending. Adult IVDs have poor innate healing potential due to low vascularity and cellularity. Degenerative disc disease (DDD) generally arises from the disruption of the homeostasis maintained by the structures of the IVD, and genetic and environmental factors can accelerate the progression of the disease. Impaired cell metabolism due to pH alteration and poor nutrition may lead to autophagy and disruption of the homeostasis within the IVD and thus plays a key role in DDD etiology. To develop regenerative therapies for degenerated discs, future studies must aim to restore both anatomical and biomechanical properties of the IVDs. The objective of this review is to give a detailed overview about anatomical, radiological, and biomechanical features of the IVDs as well as discuss the structural and functional changes that occur during the degeneration process.

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Introduction: Diabetes has long been implicated as a major risk factor for intervertebral disc (IVD) degeneration, interfering with molecular signaling and matrix biochemistry, which ultimately aggravates the progression of the disease. Glucose content has been previously shown to influence structural and compositional changes in engineered discs in vitro, impeding fiber formation and mechanical stability.Methods: In this study, we investigated the impact of diabetic hyperglycemia on young IVDs by assessing biochemical composition, collagen fiber architecture, and mechanical behavior of discs harvested from 3-to 4-month-old db/db mouse caudal spines.Results: We found that discs taken from diabetic mice with elevated blood glucose levels demonstrated an increase in total glycosaminoglycan and collagen content, but comparable advanced glycation end products (AGE) levels to wild-type discs. Diabetic discs also contained ill-defined boundaries between the nucleus pulposus and annulus fibrosus, with the latter showing a disorganized and unaligned collagen fiber network at this same boundary.Conclusions: These compositional and structural changes had a detrimental effect on function, as the diabetic discs were twice as stiff as their wild-type counterparts and demonstrated a significant resistance to deformation. These results indicate that diabetes may predispose the young disc to DDD later in life by altering patterns of extracellular matrix deposition, fiber formation, and motion segment mechanics independently of AGE accumulation.