Chemical and mechanical characterization of hyaluronic acid hydrogel cross-linked with polyethylen glycol and its use in dermatology.

Hydrogels based on hyaluronic acid are used to restore volume, hydration, and skin tone, as well as to correct scars, asymmetries or defects of the soft tissue. Hyaluronic acid is often chemically crosslinked with different crosslinking agents in order to improve its mechanical and biological properties. Here we focused on defining the chemical and mechanical characterization of a new hydrogel with specific characteristics: hyaluronic acid polyethylene glycol (PEG)-crosslinked with a high concentration of hyaluronic acid (28 mg/mL), manufactured by MatexLab Spa, via Carlo Urbani 2, ang Via Enrico Fermi, Brindisi, Italy. We made a quantitative and qualitative analysis of the content of sodium hyaluronate in the hydrogel after polymerization and sterilization processes and also evaluated histologically the bio integration of these hydrogels in the cutaneous soft tissues. The results suggest that hyaluronic acid hydrogel PEG-crosslinked have great bio integration, great chemical and mechanical properties, compared with other products available on the market, that are cross-linked with different cross-linking agents. The nontoxicity and nonimmunogenicity of PEG guarantee the lack of allergic and immunological reactions. The PEG-crosslinking technology guarantees a high duration time of the implanted hydrogel because of more resistant physiological degradation.

Chemical Characterization of Hydrogels Crosslinked with Polyethylene Glycol for Soft Tissue Augmentation.

BACKGROUND: Hyaluronic acid (HA) based hydrogels for esthetic applications found widespread use. HA should be crosslinked for this application to achieve the correct viscoelastic properties and avoid fast degradation by the hyaluronidase enzyme naturally present in the skin: these properties are controlled by the amount of crosslinker and the fraction that is effectively crosslinked (i.e. that binds two HA chains). AIM: Crosslinking by polyethylene glycol diglycidyl ether (PEGDE) has been more recently introduced and showed attractive features in terms of viscoelastic properties and reduced biodegradation. Aim of this paper is to define a method for the determination of the crosslinking properties of these recently introduced fillers, method that is lacking at the moment. MATERIAL AND METHOD: The percentage of crosslinker and the fraction that is effectively crosslinked were determined by proton Nuclear Magnetic Resonance (1H NMR) and by 13C NMR, respectively. The filler were preliminarily washed with acetonitrile to remove residual PEG and then digested by hyaluronidase to obtain a sample that can be analysed by NMR. RESULTS: The crosslinking parameters were determined in four samples of NEAUVIA PEG-crosslinked dermal fillers (produced by MatexLab S.p.A., Italy). The percentage of crosslinker was between 2.8% and 6.2% of HA, whereas the effective crosslinker ratios were between 0.07 and 0.16 (ratio between the moles of effectively crosslinked PEG and total moles of PEG). Moreover, a digestion procedure alternative to enzymatic digestion, based on acidic hydrolysis, was successfully tested for the determination of crosslinker percentage. CONCLUSIONS: The proposed method successfully determined the two crosslinking parameters in PEG-crosslinked dermal fillers. The estimated percentage of crosslinker is similar to previously reported data for other crosslinkers, whereas the effective crosslinker ratio is lower for PEG crosslinked hydrogels.

In Vitro Evaluation of the Sensitivity of a Hyaluronic Acid PEG Cross-Linked to Bovine Testes Hyaluronidase.

Neauvia Intense is biocompatible, injectable hyaluronic acid (HA) filler PEG cross-linked for facial soft-tissue augmentation that provides volume to tissues. The aim of the present study is to evaluate the sensitivity of Neauvia Intense in hyaluronidase from bovine testes in a time-course analysis. The test is based on the colourimetric determination of the N-acetyl - D - glucosamine (NAG) released by the hyaluronidase in standardised conditions. The in vitro conditions involve the treatment of Neauvia Intense with a known concentration of the enzyme (6080U/ml). The NAG content was determined at different times to assess the kinetics of the degradation (1h, 3h, 6h, 24h, 48h, 72h, 120h, and 168h); the Ehrlich's reagent was used for the colourimetric quantification, by the method described by Reissing and colleagues. The intensity of the violet colour developed after the chemical reaction was proportional to the NAG present in each sample. A microplate reader at 585 nm read the absorbance. The amount of NAG released by the product was proportional to the time of incubation with bovine hyaluronidase, reaching a plateau after 168 hours.

Study of polymer particles suspensions for electrophoretic deposition.

Recently a great interest has been expressed in electrophoretic deposition (EPD) of polymers, both as particles and as chains. It is generally accepted that also for polymer particles, the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory is valid, therefore, in principle, polymer suspensions suitable for EPD could be easily obtained by dispersing polymer particles in an aqueous or nonaqueous medium. Nevertheless, this work demonstrated that in order to obtain good quality deposits based on poly(ether ether ketone) (PEEK) and poly(tetrafluoroethylene) (PTFE), some additives have to be used. In the case of PEEK, a dispersant providing citrate anions was successfully used, whereas for PTFE a steric suspension stabilization was reached by adding polyvinylpyrrolidone (PVP). In such a way, codeposition of PEEK and PTFE was achieved. The efficiency of the EPD process was demonstrated by means of differential scanning calorimetry (DSC) measurements. A thermal program consisting of heat/cool/heat cycles at a low rate was used in order to evaluate the crystalline amount of each polymer in the deposits. In order to explain the obtained results, it needed to also consider the dimension and structural characteristic of the polymer particles.