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

Abstract

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.

Are Bacterial Growth and/or Chemotaxis Increased by Filler Injections? Implications for the Pathogenesis and Treatment of Filler-Related Granulomas

“…In spite of that, antibiotics are used as a treatment of this kind of medical complications though the role of antibiotics either as anti-inflammatory or bactericidal drugs is disputable. Although we were not able to demonstrate their anti-inflammatory effect in two previous in vitro studies [21,22], other authors obtained different results. Webster et al [34], in an elegant study, showed that tetracyclines and ciprofloxacin dose-dependently inhibited granuloma formation in vitro.…”

“…Our data partially agree with our clinical series, wherein bacteria were recovered in a few cases, and the response to antibiotics was unfavorable [10,16,18]. In other experiments, we did not find increased lymphokine production, except for mainly IFN-γ and IL-2, when human peripheral blood mononuclear cells were cultured with biomaterials in combination with bacterial lipopolysaccharide [21,22]. …”

“…There is no doubt that biomaterials may provoke local or systemic chronic granulomatous immune-mediated reactions in some individuals [1,7,8,9,12,16,18,19,20,21,22]. The exact cause of these adverse effects is elusive.…”

“…Blood samples were taken from 110 patients of this cohort. Thereafter, peripheral blood mononuclear cells were obtained according to standard procedures to perform different other studies apart from those mentioned above [11,18,19,20,21,22]. …”

Probable biofilm formation in the cheek as a complication of soft tissue filler resulting from improper endodontic treatment of tooth 16

“…12 With regard to the effect of hyaluronic acid on inflammatory mediators, immune cells, and oxidative stress, it has been observed that hyaluronic acid produces a low-grade inflammatory response when it stimulates peripheral blood mononuclear cells. 13 The same study also showed a slight increase in the production of interferon-γ and higher expression of CD25, CD69, and CD71 in phytohemagglutininstimulated peripheral blood mononuclear cells from patients who underwent hyaluronic acid filler injections and displayed adverse effects.…”