A Guide for Using Mechanical Stimulation to Enhance Tissue-Engineered Articular Cartilage Properties

Abstract

The use of tissue-engineered articular cartilage (TEAC) constructs has the potential to become a powerful treatment option for cartilage lesions resulting from trauma or early stages of pathology. Although fundamental tissue-engineering strategies based on the use of scaffolds, cells, and signals have been developed, techniques that lead to biomimetic AC constructs that can be translated to in vivo use are yet to be fully confirmed. Mechanical stimulation during tissue culture can be an effective strategy to enhance the mechanical, structural, and cellular properties of tissue-engineered constructs toward mimicking those of native AC. This review focuses on the use of mechanical stimulation to attain and enhance the properties of AC constructs needed to translate these implants to the clinic. In vivo, mechanical loading at maximal and supramaximal physiological levels has been shown to be detrimental to AC through the development of degenerative changes. In contrast, multiple studies have revealed that during culture, mechanical stimulation within narrow ranges of magnitude and duration can produce anisotropic, mechanically robust AC constructs with high cellular viability. Significant progress has been made in evaluating a variety of mechanical stimulation techniques on TEAC, either alone or in combination with other stimuli. These advancements include determining and optimizing efficacious loading parameters (e.g., duration and frequency) to yield improvements in construct design criteria, such as collagen II content, compressive stiffness, cell viability, and fiber organization. With the advancement of mechanical stimulation as a potent strategy in AC tissue engineering, a compendium detailing the results achievable by various stimulus regimens would be of great use for researchers in academia and industry. The objective is to list the qualitative and quantitative effects that can be attained when direct compression, hydrostatic pressure, shear, and tensile loading are used to tissue-engineer AC. Our goal is to provide a practical guide to their use and optimization of loading parameters. For each loading condition, we will also present and discuss benefits and limitations of bioreactor configurations that have been used. The intent is for this review to serve as a reference for including mechanical stimulation strategies as part of AC construct culture regimens.

Extruded Bioreactor Perfusion Culture Supports the Chondrogenic Differentiation of Human Mesenchymal Stem/Stromal Cells in 3D Porous Poly(ɛ‐Caprolactone) Scaffolds

“…The role of mechanical signals in the regulation of MSC fate has been demonstrated and explored for a broad range of tissue engineering strategies . In CTE, mechanical stimuli such as fluid flow‐induced shear stress, compression, tension, and hydrostatic pressure have been applied alone or combined using bioreactor systems and demonstrated to promote the chondrogenic potential of MSC . However, the molecular mechanisms involved in the MSC mechanotransduction signaling are not fully understood .…”

“…Flow perfusion has been applied for the production of both MSC‐based tissue‐engineered bone and cartilage . Different magnitudes of shear stress generated by fluid perfusion have been reported to result in distinct engineered cartilage phenotypes . Therefore, more studies on the effects of fluid perfusion on MSC chondrogenic differentiation are needed to deepen our understanding of the underlying molecular signaling involved and to define boundary stimulation conditions for magnitudes and regimes envisaging improved protocols for CTE approaches.…”

“…MSC differentiation fate regulation through perfusion has also been predicted to be dependent on the flow rate magnitudes involved . While there are studies reporting the positive effect of fluid perfusion in MSC chondrogenic differentiation on tissue engineering scaffolds, others have demonstrated detrimental effects such as tissue hypertrophy, reduced GAG production, and lower cell viabilities .…”

Bioreactor for mobilization of mesenchymal stem/stromal cells into scaffolds under mechanical stimulation: Preliminary results

“…The elastic rings ( Fig 2D) were made following the instructions of the manufacturer (Silicone Rubber high elasticity, Glorex AG, Füllinsdorf, Switzerland). Then, the silicone was cast in a (4) is placed over them, which is held in place by the elastic ring (3) and a mesh above it (5). The mesh is kept in place by a ring anchored to the construction using screws (6).…”

“…In an avascular tissue where nutrients and cytokines are mainly distributed by diffusion, joint motion assists to the transport rate of solutes [3]. Mechanical activity in joints supports the proper functionality of chondrocytes, improves ECM content, promotes glycosaminoglycan synthesis, and fiber organization [4,5]. Furthermore, mechanical stimulation contributes to the synthesis of ECM components by chondrocytes even if isolated from patients with osteoarthritis [6].…”