Richard A. Berg

Crosslinked hyaluronic acid dermal fillers : a comparison of rheological properties

Temporary dermal fillers composed of crosslinked hyaluronic acid (XLHA) are space filling gels that are readily available in the United States and Europe. Several families of dermal fillers based on XLHA are now available and here we compare the physical and rheological properties of these fillers to the clinical effectiveness. The XLHA fillers are prepared with different crosslinkers, using HA isolated from different sources, have different particle sizes, and differ substantially in rheological properties. For these fillers, the magnitude of the complex viscosity, |eta*|, varies by a factor of 20, the magnitude of the complex rigidity modulus, |G*|, and the magnitude of the complex compliance, |J*| vary by a factor of 10, the percent elasticity varies from 58% to 89.9%, and the tan delta varies from 0.11 to 0.70. The available clinical data cannot be correlated with either the oscillatory dynamic or steady flow rotational rheological properties of the various fillers. However, the clinical data appear to correlate strongly with the total concentration of XLHA in the products and to a lesser extent with percent elasticity. Hence, our data suggest the following correlation: dermal filler persistence = [polymer] x [% elasticity] and the clinical persistence of a dermal filler composed of XLHA is dominated by the mass and elasticity of the material implanted. This work predicts that the development of future XLHA dermal filler formulations should focus on increasing the polymer concentration and elasticity to improve the clinical persistence.

Reduction of epidural fibrosis in lumbar surgery with Oxiplex adhesion barriers of carboxymethylcellulose and polyethylene oxide.

BACKGROUND CONTEXT Postsurgical epidural adhesions and fibrosis after surgery for lumbar disc herniation are a consequence of normal wound healing. The presence of fibrosis renders reoperations risky, and in some patients fibrosis may lead to nerve root tethering. PURPOSE One approach to minimizing the risk of developing epidural adhesions is to provide a barrier between the dural membrane and the healing connective tissues. The purpose of these studies was to evaluate such a barrier device. STUDY DESIGN/SETTING In vivo investigation in an animal model at a university laboratory. PATIENT SAMPLE Rabbit. OUTCOME MEASURES Gross and histomorphic evaluation. METHODS Barriers comprised of carboxymethylcellulose (CMC) and polyethylene oxide (PEO) (Oxiplex; FzioMed, Inc., San Luis Obispo, CA) were studied as devices to reduce epidural adhesion formation in rabbit laminotomy and laminectomy models. The barriers tested were either a gel alone (gel) or a gel covered with a film (gel/film combination). Two laminotomy or laminectomy sites (depending on the surgical method) were created in each rabbit at L4 and L6. One site was treated with a CMC/PEO gel, or CMC/PEO gel/film combination, and the other site served as a surgical control. Two surgical models that differed in the extent of adhesion formation at untreated injury sites and the method of injury generation were used. RESULTS Model A, which did not incorporate dural abrasion, resulted in up to 40% adhesion-free laminectomy sites in controls. Model B, which did incorporate abrasion of the dural membrane, resulted in less than 10% adhesion-free laminotomy sites in controls. Compositions of CMC/PEO gels (2.5% to 10% PEO) and films (22.5% PEO) were tested in both models. Efficacy parameters included measuring the number of sites free of epidural fibrosis and reduction in the severity of fibrosis (adhesions). Both gels and gel/film combinations consistently reduced the frequency and the extent of epidural fibrosis in both models. Gels of CMC/PEO containing a higher content of PEO (10%) and a higher molecular weight of PEO (4.4 mD) were most effective in Model B and resulted in up to 84% laminotomy sites with minimal or no epidural fibrosis, whereas controls exhibited over 90% of the sites with epidural fibrosis. Histological evaluation of the surgical sites indicated that the reduction of epidural fibrosis was accompanied by normal bone healing. In addition, these experiments demonstrated that the gel/film combination provided no additional benefit to that obtained by the gel alone. CONCLUSIONS Gels of CMC/PEO reduced epidural fibrosis and did not impair normal heal ing.

Temporary Polysaccharide Dermal Fillers: A Model for Persistence Based on Physical Properties

BACKGROUND The physical and chemical properties that control the clinical persistence of temporary dermal fillers are not well understood. Discovering the relationship between the clinical performance and physical properties of temporary fillers may stimulate the design of future, high‐performance fillers. OBJECTIVE Described here is the rheology of polysaccharide dermal fillers composed of cross‐linked hyaluronic acid (XLHA) or un‐cross‐linked sodium carboxymethylcellulose (CMC) and polyethylene oxide (PEO). Using measured rheology data and published clinical study data, we have developed a predictive model for the persistence of polysaccharide‐containing dermal fillers. METHODS AND MATERIALS The XLHA dermal fillers were obtained from commercial sources. The CMC/PEO dermal filler formulation was prepared in house. The rheologic properties of the polysaccharide fillers were measured and related to comparative clinical persistence data available from controlled clinical studies. RESULTS The clinical persistence of the polysaccharide dermal fillers correlates linearly with the concentration of polymer in the formulation divided by the tan δ (G″/G′). SUMMARY The work described here has shown that a model relating the concentration of the polysaccharide and the tan δ of the formulation can predict the comparative clinical persistence of XLHA and CMC/PEO dermal fillers. Both authors are employees of FzioMed, which supported this study.