Regenerative Engineering Animal Models for Knee Osteoarthritis

Abstract

Osteoarthritis (OA) of the knee is the most common synovial joint disorder worldwide, with a growing incidence due to increasing rates of obesity and an aging population. A significant amount of research is currently being conducted to further our understanding of the pathophysiology of knee osteoarthritis to design less invasive and more effective treatment options once conservative management has failed. Regenerative engineering techniques have shown promising preclinical results in treating OA due to their innovative approaches and have emerged as a popular area of study. To investigate these therapeutics, animal models of OA have been used in preclinical trials. There are various mechanisms by which OA can be induced in the knee/stifle of animals that are classified by the etiology of the OA that they are designed to recapitulate. Thus, it is essential to utilize the correct animal model in studies that are investigating regenerative engineering techniques for proper translation of efficacy into clinical trials. This review discusses the various animal models of OA that may be used in preclinical regenerative engineering trials and the corresponding classification system. Lay Summary Osteoarthritis (OA) of the knee is the most common synovial joint disease worldwide, with high rates of occurrence due to an increase in obesity and an aging population. A great deal of research is currently underway to further our understanding of the causes of osteoarthritis, to design more effective treatments. The emergence of regenerative engineering has provided physicians and investigators with unique opportunities to join ideas in tackling human diseases such as OA. Once the concept is proven to work, the initial procedure for the evaluation of a treatment solution begins with an animal model. Thus, it is essential to utilize a suitable animal model that reflects the particular ailment in regenerative engineering studies for proper translation to human patients as each model has associated advantages and disadvantages. There are various ways by which OA can occur in the knee joint, which are classified according to the particular cause of the OA. This review discusses the various animal models of OA that may be used in preclinical regenerative engineering investigations and the corresponding classification system.

Osteoarthritis: Pathogenesis, Animal Models, and New Regenerative Therapies

“…In some strains of mice, such as STR/ort and C57BL/6, the genetic predisposition to developing spontaneous OA, even in very young animals (18 weeks of age), was confirmed. Other mouse strains, such as CBA, have been described as resistant to the development of OA (as a negative animal model) [39].…”

“…Genetic engineering explores gene knockouts to determine the genetic factors involved in the predisposition to OA [39] Among the major advantages of the mouse as an animal model in OA studies is the ability for the genetic modification or preparation of specific strains, particularly those susceptible or resistant to OA. In the case of knockout mice, lacking some proteases or collagen type IX alpha one gene inactivation could make them resistant to developing OA [17] STR/ort mice can be used to show a correlation between OA and chondrocyte metabolism, and Col2a1 knockout mice have a higher incidence (60-90%) of natural OA than wild-type mice [17,39].…”

“…Although genetic engineering plays a crucial role in understanding the mechanisms of OA and the impact of genetics on the development of OA, the use of these models in the development of appropriate treatment options is limited [17,39] In experiments based on animal models, the procedure's success also depends on the surgical procedure's reproducibility on all animal subjects. Some of these problems can be resolved using non-invasive models.…”

“…Recent developments in biomedical sciences have provided scientists with alternative approaches to tissue repair. Nevertheless, this branch of science requires further progress in order to achieve the most favorable strategies and solutions [39].…”

Oxygen-Generating Biomaterials for Translational Bone Regenerative Engineering

“…Although metal implants can overcome these drawbacks, they lack regeneration features and may cause osteolysis and aseptic loosening. The current strategies’ constraints signify a paradigm shift to accomplish regenerative engineering strategies. , The strategy of regenerative engineering was first introduced by our group in 2012 and has converged the technology advancements in different areas such as advanced materials science, stem cell science, and areas of developed biology toward complex tissue regeneration. − An exemplary engineered tissue graft successfully substitutes the strut platform for the regenerating milieu, sufficiently endures mechanical forces, and biodegrades in accordance with newly formed tissue. , As such, the definitive objective of utilizing engineered biomaterials in regenerative engineering is to imitate native tissue’s biophysical characteristics to evoke the innate healing response, enhance osteogenesis, and revive functionality …”