Tissue Reactions to Engineered Cartilage Based on Poly-L-Lactic Acid Scaffolds

Abstract

Tissue reactions against poly-L-lactic acid (PLLA) in engineered cartilage may influence the size or maturity of regenerative tissue. To understand the biological events in these reactions, we subcutaneously transplanted engineered constructs of PLLA scaffolds with or without human chondrocytes or atelocollagen in nude mice and evaluated neovascularization and macrophage activation, which can be assessed even in nude mice. Although not showing cartilage regeneration, PLLA alone demonstrated dense localization of macrophages and blood vessels, as well as a high level of interleukin-1 beta and tissue hemoglobin at 2 and 8 weeks. Otherwise, constructs with PLLA and chondrocytes with or without atelocollagen (PLLA/cell/gel or PLLA/cell) formed mature cartilage by 8 weeks, which was more prominent in PLLA/cell/gel. Although accumulation of macrophages and blood vessels in PLLA/cell/gel and PLLA/cell was comparable with that in PLLA at 2 weeks, that in PLLA/cell/gel markedly decreased by 8 weeks, with blood vessels and macrophages excluded into non-cartilage areas. Macrophage migration inhibitory factor could be involved in these suppressed tissue reactions, because it was expressed in chondrocytes of engineered cartilage. Intense tissue reactions inevitably occurred in biopolymers alone, but it is possible that maturation of engineered cartilage suppressed these reactions, which may contribute to circumventing deformity or malformation of engineered tissues.