title: Role for interleukin 1alpha 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.
authors.affiliation: Center for Tissue Engineering, University of Massachusetts Medical Center, Worcester, Massachusetts, USA. nicole.rotter@hno.uni-luebeck.de
authors.forename: Nicole
authors.initials: N
authors.lastname: Rotter
authors.forename: Feodor
authors.initials: F
authors.lastname: Ung
authors.forename: Amit K
authors.initials: AK
authors.lastname: Roy
authors.forename: Martin
authors.initials: M
authors.lastname: Vacanti
authors.forename: Roland D
authors.initials: RD
authors.lastname: Eavey
authors.forename: Charles A
authors.initials: CA
authors.lastname: Vacanti
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Bonassar
mesh_terms: D020341:Absorbable Implants / Q000662:veterinary; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation; D004425:Ear Cartilage / Q000166:cytology; D020007:Implants, Experimental; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D019344:Lactic Acid / Q000494:pharmacology*; D008297:Male; D011091:Polyesters / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D013552:Swine; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods; D014182:Transplantation, Autologous
chemical_list: D001672:Biocompatible Materials; C460779:Ethisorb; D007375:Interleukin-1; D011091:Polyesters; D011108:Polymers; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)