Models of Disease

Abstract

Osteochondral (OC) lesions are a major cause of chronic musculoskeletal pain and functional disability, which reduces the quality of life of the patients and entails high costs to the society. Currently, there are no effective treatments, so in vitro and in vivo disease models are critically important to obtain knowledge about the causes and to develop effective treatments for OC injuries. In vitro models are essential to clarify the causes of the disease and the subsequent design of the first barrier to test potential therapeutics. On the other hand, in vivo models are anatomically more similar to humans allowing to reproduce the pattern and progression of the lesion in a controlled scene and offering the opportunity to study the symptoms and responses to new treatments. Moreover, in vivo models are the most suitable preclinical model, being a fundamental and a mandatory step to ensure the successful transfer to clinical trials. Both in vitro and in vitro models have a number of advantages and limitation, and the choice of the most appropriate model for each study depends on many factors, such as the purpose of the study, handling or the ease to obtain, and cost, among others. In this chapter, we present the main in vitro and in vivo OC disease models that have been used over the years in the study of origin, progress, and treatment approaches of OC defects.

Three-Dimensional Cell Cultures: The Bridge between In Vitro and In Vivo Models

“…For these reasons, in vitro 3D models have become important tools in the development and testing of potential treatments and strategies to improve the regeneration process of bone, cartilage, or osteochondral interphase. On the one hand, they are useful for studying and improving the integration of the newly formed tissue with the surrounding environment [95]; on the other hand, they are considered valid 3D models for bone disease studies [96]. Indeed, 3D composite bone tissue scaffolds with both mechanical stability and drug-delivery functionality are employed to study the drug-delivery properties of statins, biocompatibility, alkaline phosphatase activity, and osteoblasts activity in vitro for the treatment of osteoporosis [97].…”

“…Osteoarthritis studies, showed complex 3D models to reproduce the osteochondral interface, involving elements of the cartilage component and the well-vascularised cartilage-to-bone transition zone [99]. These engineered constructs are multiphasic structures with a particular rigid and porous section containing osteoblasts and endothelial cells, corresponding to the subchondral bone, a hydrated and viscoelastic section containing chondrocytes to reproduce the cartilaginous region [96]. The triphasic models are the ideal system for studying the complex cellular interactions in health or disease conditions affecting this area [100,101].…”

A Roadmap of In Vitro Models in Osteoarthritis: A Focus on Their Biological Relevance in Regenerative Medicine

“…Additive manufacturing methods allowed the development of 3D biomimetic and customized scaffolds that support cell viability and functions [ 210 ]. Among 3D printing approaches, electrospinning gained considerable attention as it generates structures with the submicron resolution by reproducing specific surface topography, which is another critical aspect to consider when studying cell behavior [ 211 , 212 , 213 ]. When referring to 3D models with scaffolds, their selection covers great importance, since findings vary greatly based on their nature and architecture.…”