Shear bioreactors stimulating chondrocyte regeneration, a systematic review

Abstract

It is commonly accepted that the mechanical stimuli are important factors in the maintenance of normal structure and function of the articular cartilage. Despite extensive efforts, the cellular mechanisms underlying the responses of articular chondrocytes to mechanical stresses are not well understood. In the present review, different types of shear bioreactor and potential mechanisms that mediate and regulate the effect of shear on chondrocyte are discussed. For this review, the search of the literature was done in the PubMed, Scopus, Web of sciences databases to identify papers reporting data about shear on chondrocyte. Keywords “shear, chondrocyte, cartilage, bioreactor” were used. Studies published until the first of March 2018 were considered in this paper. The review focused on the experimental studies conducted the effect of shear stress on cartilage tissue in vivo and in vitro. In this review, both experimental studies referring to human and animal tissues were taken into account. The following articles were excluded: reviews, meta-analysis, duplicate records, letters, and papers that did not add significant information. Mechanism of shear stress on chondrocyte, briefly can be hypothesized as (1) altered expression of aggrecan and collagen type II, (2) altered cartilage oligomeric matrix protein (COMP) serum levels, consequently, organizing the arrangement binding of glycosaminoglycans, integrins, and collagen, (3) induction of apoptosis signals, (4) altered expression of integrin.

Microfluidic Biofabrication of 3D Multicellular Spheroids by Modulation of Non-geometrical Parameters

“…Alcian blue staining showed that, regardless of the flow rate, the pellet region in direct contact with culture medium was characterized by a higher amount of GAGs. This result is in accordance with several studies showing that AC metabolism is directly modulated by shear forces in a wide range of intensity (i.e., 0.01-1 Pa) acting on the cells through mechanotransduction processes and inducing the upregulation of cartilage-specific ECM components, such as GAG and other proteoglycans, as recently reviewed (Sharifi and Gharravi, 2019). It must be noted that the ACs used in this study were derived from osteoarthritic donor, albeit only macroscopically non-fibrillated regions of cartilage were harvested for cell isolation.…”

“…However, our experience with osteoarthritic chondrocytes indicates that, when cultured in the presence of suitable growth factors combinations, these cells are able to redifferentiate and produce cartilage-specific matrix, in line with literature reports that indicate this cell source as suitable for cartilage tissue-engineering applications (Stoop et al, 2007;Hsieh-Bonassera et al, 2009;Lopa et al, 2013). Based on the similar effects induced by fluid flow on ACs derived from the most diverse sources (Sharifi and Gharravi, 2019), we can reasonably speculate that although absolute amounts of GAG produced by healthy and osteoarthritic chondrocytes may differ, a similar outcome can be expected in cell response to biophysical stimulation. The observed results may either depend on a direct effect of flow rate on GAG production or be the result of a combination of biophysical and biochemical stimuli.…”

“…Finally, our results demonstrated that fluid dynamic stimulation plays a very important role also after spheroid formation influencing GAG deposition. These results are not unexpected, since in several studies, biophysical cues have been applied to stimulate 3D constructs through micro-and macro-scale systems, demonstrating their effects on chondrocyte phenotype (Raimondi et al, 2011;Mayer et al, 2016;Salinas et al, 2018;Occhetta et al, 2019;Sharifi and Gharravi, 2019). Alcian blue staining showed that, regardless of the flow rate, the pellet region in direct contact with culture medium was characterized by a higher amount of GAGs.…”

Articular Repair/Regeneration in Healthy and Inflammatory Conditions: From Advanced In Vitro to In Vivo Models

“…[50] Also, a recent systematic review discusses the different types of shear bioreactors and the mechanisms regulating the effect of shear on chondrocytes. [51] One important issue, particularly to develop strategies for drug delivery into the joints, is the introduction of hydrodynamic stimuli in in vitro models, ideally combining them with mechanical loading forces. In the last year, an osteochondral ex vivo model was established with human biopsies cultured in a CellecBiotek perfusion bioreactor to provide specifictissue nutrient media and bidirectional perfusion of signaling molecules, resembling the physiological microenvironment.…”

“…[ 50 ] Also, a recent systematic review discusses the different types of shear bioreactors and the mechanisms regulating the effect of shear on chondrocytes. [ 51 ]…”