Scaffold structure and fabrication method affect proinflammatory milieu in three‐dimensional‐cultured chondrocytes

Abstract

Cartilage tissue engineering has emerged as an attractive therapeutic option for repairing damaged cartilage tissue in the arthritic joint. High levels of pro-inflammatory cytokines present at arthritic joints can cause cartilage destruction and instability of the engineered cartilage tissue, and thus it is critical to engineer strong and stable cartilage that is resistant to the inflammatory environment. In the present study, we demonstrate that scaffolding materials with different pore sizes and fabrication methods influence the microenvironment of chondrocytes and the response of these cells to pro-inflammatory cytokines, IL-1β and TNFα. Silk scaffolds prepared using the organic solvent hexafluoroisopropanol (HFIP) as compared to an aqueous-based method, as well as those with larger pore sizes, supported the deposition of higher cartilage matrix levels and lower expression of cartilage matrix degradation-related genes, as well as lower expression of endogenous pro-inflammatory cytokines IL-1β in articular chondrocytes. These biochemical properties could be related to the physical properties of the scaffolds such as the water uptake and the tendency to leach or adsorb pro-inflammatory cytokines. Thus, scaffold structure may influence the behavior of chondrocytes by influencing the microenvironment under inflammatory conditions, and should be considered as an important component for bioengineering stable cartilage tissues.

Bombyx mori derived scaffolds and their use in cartilage regeneration: a systematic review

“…The Chondrocyte response towards scaffolds induced with pro-inflammatory cytokines [interleukins (IL-1b) and tumor necrosis factor (TNFa)] studied by Kwon suggests that silk can be a better source regarding adaptability with the microenvironment, as chondrocytes seeded on silk were still able to produce enough ECM in a traumatic condition as compared to polylactic acid (PLA) 59 . Similar conditions (IL-1b and TNFa) were applied in another study conducted by Kwon, where different pore size of silk hexafluoroisopropanol (HFIP) sponges revealed that the scaffolds with larger pore size supported high ECM production and low expression of cartilage matrix degradation genes 60 . Conversely, in some cases, cells seeded on scaffolds were supplemented with growth factors in order to enhance the ECM production 61e65 .…”

Hydrogels for Cartilage Regeneration, from Polysaccharides to Hybrids

“…However, these hydrogels, implanted alone into cartilage defects, are insufficient to generate a homogenously hyaline cartilage repair tissue. Kwon H. et al [ 168 ] demonstrated that scaffolds, with different pore size and fabrication methods, influence the microenvironment of chondrocytes and their response to proinflammatory substances. Having high levels of proinflammatory cytokines can cause cartilage destruction and instability of the engineered cartilage tissue.…”

3D in vitro modeling of the central nervous system

“…Regenerative medicine, according to the National Institute of Health (NIH), is a broad field which involves “intervention to improve the self-healing capacity of the human body by use of either scaffolding materials, biologically active molecules and cellular components”, or some combination of these components. There are many approaches within regenerative medicine, including, but not limited to: genetic engineering and subsequent implantation of cells (Lee et al, 2012), bottom-up design and synthesis of tissue constructs (Kwon et al, 2014), construction of native decellularized extracellular matrix (ECM) (Wagner et al, 2014), and regenerative methods (Klar et al, 2014), Figure 1 . Tissue engineering is a large subfield of regenerative medicine which refers to a combinatorial approach of the aforementioned components into a functional tissue or “unit” of tissue in vitro.…”