Differences in Interleukin-1 Response Between Engineered and Native Cartilage

Abstract

Unlike native cartilage explants that are used in autologous tissue transfer procedures, engineered cartilage constructs are typically highly fragile when first formed and must rely on cellular activity to develop over time. However, inflammatory cytokines such as interleukin-1alpha (IL-1alpha) are often present in target joints and may interfere with this development process. Herein we examine to what extent nascent engineered tissue is susceptible to chemical perturbations by IL-1alpha (10 ng/mL), especially when compared to native explants, and whether in vitro preconditioning may promote sufficient integrity to lessen this impact. The studies were carried out using a chemically defined medium supplemented with or without the antiinflammatory steroid dexamethasone. We find that engineered tissue (bovine chondrocytes in agarose hydrogel) at early time points (days 0 and 14) does not grow when exposed to the cytokine even temporarily, but both bovine explants and more developed engineered tissue (day 28) are able to withstand the same exposure without degradation of properties. We argue therefore that some in vitro preconditioning may be necessary to promote both sufficient mechanical integrity and the chemical fortitude without which insufficiently developed engineered constructs will not survive the harsh mechanochemical environment within the joint.

Bioactive Glass 13-93 as a Subchondral Substrate for Tissue-engineered Osteochondral Constructs: A Pilot Study

“…7D). The peak construct values achieved in this study were E Y , 743 kPa; GAG, 7.6%ww, G*, 2.8 MPa; and collagen, 6.2%ww, which compare favorably with native bovine wrist cartilage [30]. Histology showed a homogeneous extracellular matrix distribution (GAG and collagen) for constructs exposed to BG 13-93 on Days 28 to 42 (Fig.…”

“…In Study 1, at Day 42, BG 13-93-containing constructs had a mean concentration of GAG in the chondrocyte-seeded agarose gel layer of 6.29%ww, which is comparable to native bovine cartilage [30] (Fig. 4A).…”

Beneficial Effects of Cerium Oxide Nanoparticles in Development of Chondrocyte-Seeded Hydrogel Constructs and Cellular Response to Interleukin Insults

“…For instance, it has been shown that cultivating partially or fully mature engineered cartilage in vitro allows implanted tissue to withstand the harsh catabolic environment better than a freshly seeded or underdeveloped construct. 5,6 Other strategies include delivery of steroids, such as dexamethasone, or exogenous crosslinking factors. [6][7][8] However, biocompatible substances that sustainably scavenge radicals and protect de novo cartilage from an inflammatory response are more advantageous.…”

“…5,6 Other strategies include delivery of steroids, such as dexamethasone, or exogenous crosslinking factors. [6][7][8] However, biocompatible substances that sustainably scavenge radicals and protect de novo cartilage from an inflammatory response are more advantageous. In this study, we investigated the effect of cerum oxide nanoparticles in culture to act as a protectant for engineered cartilage against cytokine exposure.…”

“…We selected the IL-1a isoform for our study, because it has been shown to inhibit engineered cartilage growth and to damage developed tissue. 6,8,34 To test these hypotheses, we cultured juvenile bovine chondrocytes in an agarose hydrogel scaffold with various concentrations of nanoceria and IL-1a. We measured their mechanical and biochemical properties at certain time intervals.…”