Regenerative Engineering Animal Models for Knee Osteoarthritis.

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.

The synthetic artificial stem cell (SASC): Shifting the paradigm of cell therapy in regenerative engineering.

Stem cells are of great interest in tissue regeneration due to their ability to modulate the local microenvironment by secreting bioactive factors (collectively, secretome). However, secretome delivery through conditioned media still requires time-consuming cell isolation and maintenance and also may contain factors antagonistic to targeted tissue regeneration. We have therefore engineered a synthetic artificial stem cell (SASC) system which mimics the paracrine effect of the stem cell secretome and provides tailorability of the composition for targeted tissue regeneration. We report the first of many applications of the SASC system we have formulated to treat osteoarthritis (OA). Choosing growth factors important to chondrogenesis and encapsulating respective recombinant proteins in poly (lactic-coglycolic acid) 85:15 (PLGA) we fabricated the SASC system. We compared the antiinflammatory and chondroprotective effects of SASC to that of adipose-derived stem cells (ADSCs) using in vitro interleukin 1B-induced and in vivo collagenase-induced osteoarthritis rodent models. We have designed SASC as an injectable therapy with controlled release of the formulated secretome. In vitro, SASC showed significant antiinflammatory and chondroprotective effects as seen by the up-regulation of SOX9 and reduction of nitric oxide, ADAMTS5, and PRG4 genes compared to ADSCs. In vivo, treatment with SASC and ADSCs significantly attenuated cartilage degeneration and improved the biomechanical properties of the articular cartilage in comparison to OA control. This SASC system demonstrates the feasibility of developing a completely synthetic, tailorable stem cell secretome which reinforces the possibility of developing a new therapeutic strategy that provides better control over targeted tissue engineering applications.

Selective Unique Signs of Meniscus Tears as Visualized by Magnetic Resonance Imaging.

ABSTRACT: The meniscus is an organized collection of fibrocartilaginous tissue that is located between the femoral condyles and the tibial plateau of the knee which primarily assists with load transmission. The complex composition of articulating soft-tissue structures in the knee causes the menisci to become a common source of injury, especially in the realm of athletic trauma. Magnetic resonance imaging (MRI) has become the imaging modality of choice for evaluating patients with suspected meniscal pathology because of its numerous advantages over plain radiographs. Most forms of meniscal tears have classic MRI findings and are used in correlation with physical examination findings to confirm or rule out a diagnosis. These imaging findings are referred to as signs and have been well studied, and the associated eponyms for each sign are well published throughout the literature. This article will review and describe a unique selection of meniscal pathology as visualized by MRI that is more commonly published in musculoskeletal radiology literature when compared with orthopedics and sports medicine literature.