Inflammatory signals in the development of tissue-engineered soft tissue

Scaffolds with 400 μm pores constructed from hyaluronan modified by benzyl esterification of the carboxylic acid groups (HYAFF-11) and viscous gels created from dodecyl-amidation of hyaluronan (HYADD-3) were implanted subcutaneously into rats for periods of up to 26 and 12 weeks, respectively. Tissue explants were infiltrated with methacrylate resin, sectioned and stained with a broad panel of inflammatory markers in addition to conventional histological stains. Both gels and sponges became rapidly infiltrated by cells that, in the case of HYAFF sponges, did not differentiate, whilst mature adipocytes were only observed at the margins of the sponges. This was combined with sustained inflammatory antigen expression. Conversely, in the HYADD gels, only moderate inflammatory staining was observed at 4 weeks which had diminished completely by 8 weeks. Mature and maturing adipocytes were observed deep within the gels. It is hypothesised that the gels present an excellent inflammatory cytokine profile which induces macrophage infiltration, proliferation then differentiation into adipocytes and is responsible for the generation of neoadipogenesis.