Role for Interleukin 1α in the Inhibition of Chondrogenesis in Autologous Implants Using Polyglycolic Acid–Polylactic Acid Scaffolds

Abstract

Significant challenges remain in generating tissue-engineered cartilage in immunocompetent animals. Scaffold materials such as polyglycolic acid lead to significant inflammatory reactions, inhibiting homogeneous matrix synthesis. This study examined the generation of tissue-engineered cartilage, using a polyglycolic acid-polylactic acid copolymer (Ethisorb; Ethicon, Norderstedt, Germany) in an autologous immunocompetent pig model. The goals of this study were to determine the role of interleukin 1alpha (IL-1alpha) in this system and to assess the effect of serum treatment on tissue generation. Porcine auricular chondrocytes were seeded onto Ethisorb disks cultured for 1 week in medium supplemented with either fetal bovine serum or serum-free insulin-transferrin-selenium supplement. Specimens were implanted autogenously in pigs with unseeded scaffolds as controls. After 1, 4, or 8 weeks, six specimens from each group were explanted and analyzed histologically (hematoxylin and eosin, safranin O, trichrome, and Verhoeff's staining) and biochemically (glycosaminoglycan content). The presence and distribution of IL-1alpha were assessed by immunohistochemistry. Histology revealed acute inflammation surrounding degrading scaffold. Cartilage formation was observed as early as 1 week after implantation and continued to increase with time; however, homogeneous matrix synthesis was not present in any of the specimens. Strong IL-1alpha expression was detected in chondrocytes at the implant periphery and in cells in the vicinity of degrading polymer. Histologically there was no significant difference between the experimental groups with respect to the amount of matrix synthesis or inflammatory infiltration. The glycosaminoglycan content was significantly higher in the serum-free group. These results suggest that inflammatory reactions against scaffold materials and serum components lead to the production of cytokines such as IL-1alpha that may inhibit cartilage tissue formation in autologous transplant models.

Influence of the Molecular Weight of Poly(Lactide-Co-Glycolide) on theIn VivoCartilage Repair by a Construct of Poly(Lactide-Co-Glycolide)/Fibrin Gel/Mesenchymal Stem Cells/Transforming Growth Factor-β1

“…49 All these reactions will result in local inflammation after implantation, 50 and thereby impair the chondrogenesis and the consequent cartilage restoration. 51 It is found in this study that the PLGA with the highest initial Mw (177 kDa) degrades fastest at the initial stage (Fig. 2), generating more acidic olimeric compounds and thereby creating a lower pH environment upon implantation.…”

Cellulose-based scaffold materials for cartilage tissue engineering

“…It has to provide adequate elasticity and controllable degradation and resorption rates which match neo-tissue formation rates. In cartilage tissue engineering, polymeric materials already in use like polylactic acid (PLA), and polyglycolic acid-polylactic acid (PGLA) copolymer are problematic due to their mechanical stiffness, hydrophobicity and local inflammatory tissue and non-specific foreign body reactions [3][4][5]. Other materials like polyglactin [6], polyglactin-polydioxanon [7], and hyaluronic acid [8] support chondrogenic differentiation.…”

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

“…Inflammatory response or graft rejections by the host are among the major challenges for any implanted material. [1][2][3][4] In cartilage tissue engineering, several strategies have been tested to overcome these problems. 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.…”

“…31,32 Specifically, a partially reduced cerium oxide has oxygen vacancies or defects in the lattice structure, which are associated with the loss of oxygen in the reaction [Eq. (1)]. However, the nonstoichiometric oxide CeO 2 -d is readily reoxidized back to CeO 2 by oxygen.…”