Bioengineered hyaluronic acid elicited a nonantigenic T cell activation: implications from cosmetic medicine and surgery to nanomedicine.

Hyaluronan is known to act as a filling material of extracellular matrices and as an adhesive substrate for cellular migration. Consequently, it is widely used in aesthetic medicine and surgery, and it would be expected to be used in nanomedicine. Previous clinical case reports associated hyaluronic acid implants to delayed immune-mediated adverse effects. A series of experiments to evaluate immune cell activation supported by this dermal filler and nanomedical biomaterial were performed. The study comprised a total of 12 individuals. Four healthy individuals, none with cosmetically injected dermal filler, were considered as control. Five individuals carried injections of hyaluronic acid dermal filler. Three individuals carried injections of hyaluronic acid dermal filler and presented delayed adverse effects related to the dermal filler. Hyaluronic acid-stimulated peripheral blood mononuclear cells (PBMC) produced low levels of pro-inflammatory cytokines. Phytohemagglutinine (PHA)-stimulated PBMC from patients with hyaluronic implants presenting adverse effects showed a slight increase in the production of interferon (IFN)-gamma and higher expression of CD25, CD69, or CD71. In conclusion, hyaluronic acid administration elicited a laboratory evidence of immune cell activation. Production of low levels of proinflammatory cytokines in vitro could be an observation for low-grade inflammation in vivo resulting in T cell activation.