Physical Stimulation of Chondrogenic Cells In Vitro: A Review

Abstract

Background Mechanical stimuli are of crucial importance for the development and maintenance of articular cartilage. For conditioning of cartilaginous tissues, various bioreactor systems have been developed that have mainly aimed to produce cartilaginous grafts for tissue engineering applications. Emphasis has been on in vitro preconditioning, whereas the same devices could be used to attempt to predict the response of the cells in vivo or as a prescreening method before animal studies. As a result of the complexity of the load and motion patterns within an articulating joint, no bioreactor can completely recreate the in vivo situation. Questions/purposes This article aims to classify the various loading bioreactors into logical categories, highlight the response of mesenchymal stem cells and chondrocytes to the various stimuli applied, and determine which data could be used within a clinical setting. Methods We performed a Medline search using specific search terms, then selectively reviewed relevant research relating to physical stimulation of chondrogenic cells in vitro, focusing on cellular responses to the specific load applied.

Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures

“…The requirement of a well-defined movement pattern during in vivo joint and articular cartilage formation in murine and avian embryos has also been known [38,39]. To investigate the effects of external mechanical stimuli on skeletal tissues, many different research groups have designed and developed bioreactors that can apply compressive forces (both constant and intermittent), hydrostatic pressure, tensile strain and shear stress (reviewed by Grad and colleagues [40]). The main advantage of the custom-made bioreactor applied in this study is that it exerts biomechanical stimuli that are combined in nature (hydrostatic pressure and shear stress) and thus more closely models the biomechanical environment articular chondrocytes encounter during locomotion.…”

New perspectives for articular cartilage repair treatment through tissue engineering: A contemporary review

“…Advantages of this procedure are a more uniform cell distribution, avoidance of periosteal harvest and implantation, and increased technical ease without the need for suturing to adjacent articular cartilage. These scaffold-less platforms develop a robust ECM framework of their own and permit longterm maintenance of phenotype, at least in long-term in include hydrogels made from poly(ethylene glycol) diacrylate (PEGDA) [7,[11][12][13]41,42] , collagen [43] , fibrin [44,45] , agarose, and synthetic peptides [46,47] ; sponge-like scaffolds manufactured from materials such as collagen, polyglycolic acid, polylactic acid [48] , and polyurethane [49] ; materials with a naturally-occurring porous structure, such as coral, devitalized articular cartilage [50] , and hyaluronan based scaffolds [51] . The three-dimensional scaffold provides the structural support for cell contact and matrix deposition Musumeci G et vitro culture, and can improve biophysical properties by mechanical loading.…”

Tissue Engineering for Tissue and Organ Regeneration

“…Such engineered tissues can potentially be utilized for tissue replacement strategies, for pharmacological screening of agents for therapeutic or toxic effects, or to gain insight into tissue developmental processes. Cartilage tissue, engineered using this triad of components often exhibit hyaline cartilage morphology, but the tissue has inferior mechanical properties when compared to native joint cartilage (Grad et al, 2011;. A fourth component of tissue engineering, namely mechanical stimulation has been added to the classical triad in order to better replicate the in vivo environment of joint cartilage (Grad et al, 2011;.…”

“…Cartilage tissue, engineered using this triad of components often exhibit hyaline cartilage morphology, but the tissue has inferior mechanical properties when compared to native joint cartilage (Grad et al, 2011;. A fourth component of tissue engineering, namely mechanical stimulation has been added to the classical triad in order to better replicate the in vivo environment of joint cartilage (Grad et al, 2011;. Using this "quartet" of tissue engineering (cells, scaffolds, cytokines, and mechanical stimuli), cartilage with better mechanical properties has been produced.…”

“…When compared to static cultures, bioreactors offer a number of advantages such as uniformed distribution and increased mass transfer, control of pH, temperature, gas supply (O 2 and CO 2 ), nutrients, waste product removal, and the opportunity to incorporate mechanical stimuli. Detailed reviews on the general concepts of bioreactors for tissue engineering and the application of bioreactors for the purpose of cartilage engineering are available (Godara et al, 2008;Portner et al, 2009;Haasper et al, 2008;Huang et al, 2010b;Concaro et al, 2009;Grad et al, 2011). Selected physical outcome parameters used in cartilage engineering in defined and described in Text Box 1.…”