Dilutional rheology of Radiesse: Implications for regeneration and vascular safety.

BACKGROUND: Calcium hydroxylapatite-carboxymethylcellulose (CaHA-CMC) injectables have emerged as dual-purpose fillers with bioregenerative and direct filling capabilities. AIMS: This study investigates the rheological properties of CaHA-CMC and its CMC carrier gel at various dilutions. METHODS: The storage modulus (G'), loss modulus (G″), complex viscosity (η*), loss factor (tan δ), cohesivity, and extrusion force were evaluated for a range of CaHA-CMC aqueous dilutions with an oscillatory rheometer, drop weight testing, and force analysis, respectively. RESULTS: Results revealed a significant decrease in G', η*, and increase in tan(δ) with increasing dilution, indicating a decline in the product's direct filling capabilities. Cohesivity decreased dramatically with dilution, potentially enhancing tissue biointegration and the product's biostimulatory effects. The CMC gel carrier displayed inelastic and non-resilient properties, with rheological changes differing from CaHA-CMC. Dilutional rheology was also correlated with previously published dilution-dependent biostimulatory data where hyperdiluted CaHA-CMC (>1:2) demonstrated a regenerative profile and diluted or hypodiluted mixtures retained meaningful filling properties and increased regeneration. CONCLUSIONS: These findings offer a continuum for tailoring the product's rheological profile to match specific tissue requirements. Customizable rheology allows CaHA-CMC to be tuned for either filling and contouring or optimal regenerative effects. Importantly, safety implications related to vascular occlusion suggest that dilutional rheomodulation decreases the risk of vascular events. In conclusion, this study highlights the significant impact of aqueous dilution on the rheological properties of CaHA-CMC and its carrier gel. The findings support the clinical application of tailored dilutions to achieve desired outcomes, providing versatility and safety for aesthetic applications.

Comparison of Physicochemical Characteristics and Biostimulatory Functions in Two Calcium Hydroxyapatite-Based Dermal Fillers.

BACKGROUND:   Dermal fillers containing calcium hydroxyapatite (CaHA) are categorized as biostimulatory. However, differences in CaHA biomaterial likely affect the resultant induction of collagen synthesis, and variability in microsphere shape and size likely influences a patient’s immune response. This study compares 2 CaHA based fillers: one suspended in carboxymethylcellulose (denoted "CaHA/CMC"), and one crosslinked with 1,4-butanediol diglycidyl ether to hyaluronic acid (denoted "CaHA/HA"). OBJECTIVE: To characterize CaHA/CMC and CaHA/HA fillers to stimulate in vitro collagen biosynthesis. METHODS: Physicochemical evaluations included G′ and extrusion force. Scanning electron microscopy (SEM) was used to characterize isolated CaHA microspheres and freeze-dried formulations. Collagen I and III expression were evaluated using immunofluorescence. RESULTS: CaHA/CMC showed higher G′ (P<0.001) and lower extrusion force (P=0.0003), with uniform polymeric-matrix interactions, compared with CaHA/HA. On SEM, isolated microspheres and freeze-dried CaHA/CMC showed round and smooth surfaced microspheres of similar size. Isolated microspheres and freeze-dried CaHA/HA showed nonhomogeneous, broken microspheres, of various sizes, with fragments embedded in the polymer matrix. Although both fillers induced collagen III expression, only CaHA/CMC induced longer-lasting collagen I expression, with increases of 123% (P=0.007) and 164% (P<0.0001) at 2 and 5 mg/mL, respectively, compared with control. CaHA/CMC also increased collagen I expression at equivalent CaHA microsphere concentrations at 2 (P=0.0052) and 5 mg/mL (P<0.0001), compared with CaHA/HA. CONCLUSION: The physicochemical characteristics selected for evaluation were more favorable for CaHA/CMC than CaHA/HA. When compared with CaHA/HA, the smooth, homogeneous microsphere composition of CaHA/CMC promoted significantly more collagen I biosynthesis, an essential process for tissue augmentation and long-lasting aesthetic improvement. Citation: Kunzler C, Hartmann C, Nowag B, et al. Comparison of physicochemical characteristics and biostimulatory functions in two calcium hydroxyapatite-based dermal fillers. J Drugs Dermatol. 2023;22(9):910-916. doi:10.36849/JDD.7684.

Development of emulsification resistant heavier-than-water tamponades using high molecular weight silicone oil polymers.

PURPOSE: Developing new blends of heavier-than-water silicone oil tamponade agents containing high molecular weight polydimethylsiloxane polymer for use in vitreoretinal surgery. MATERIALS AND METHODS: The viscoelastic properties of heavier-than-water silicone oil blends (30.5% F6H8 + 69.5% polydimethylsiloxane) containing high molecular weight polymer additive at increasing concentrations were measured using a controlled-stress rheometer (TA Instruments Rheolyst AR 1000 N). Emulsification of the blends was induced using a sonication device and a pluronic surfactant as a strong emulsifier. The percentage emulsion area was photographed and measured using ImageJ software. In a second in vitro emulsification assessment, silicone oil blends were dispersed using a high shear homogenizer and the oil-in-water droplets were counted using a coulter counter particle analyser. RESULTS: The addition of the high molecular weight polymer increased shear viscosity and viscoelasticity of the oil blends, which were measureable and to some extent predictable. The in vitro emulsification models produced contradictory results. This demonstrates the difficulty of designing and using in vitro models to evaluate the emulsification tendency of tamponade agents in vivo. CONCLUSION: Addition of a high molecular weight polymer to heavy silicone oil can increase the viscoelasticity. These findings might contribute to the development of emulsification resistant heavy silicone oils.

Development and initial experience with a colored perfluorocarbon liquid for intraocular tamponade in vitreoretinal surgery.

PURPOSE: To present the development and initial experience of a novel colored perfluorocarbon liquid (PFCL) in vitreoretinal surgery. METHODS: This was an experimental laboratory study and prospective human interventional study. F6H8 (Fluoron GmbH) was colored by adding 0.3 g/L blue anthraquinone dye. Subsequently, 20% colored F6H8 was prepared by mixing with perfluorooctane or perfluorodecalin (Fluoron GmbH). The novel product is not yet FDA approved for human application. In the laboratory, the colored PFCL was covered with 1) uncolored PFCL, 2) BSS, and 3) silicone oil. Cell toxicity was evaluated in L929 mouse fibroblasts using a growth inhibition assay. Porcine ex vivo eyes were evaluated after vitrectomy followed by intravitreal and subretinal colored PFCL infusion. A pilot, prospective, noncomparative interventional study was conducted in patients with retinal detachment with proliferative vitreoretinopathy (PVR). RESULTS: The density of the colored PFLC mixture was 1.664 g/cm for perfluorooctane and 1.802 g/cm for perfluorodecalin. There was no relevant cell growth inhibition with any concentration of colored PFCL tested. Experiments in pigs revealed that infusion of the colored PFCL caused neither staining of the internal limiting membrane nor intravitreal residual droplets. In the prospective study, 9 eyes (75%) underwent surgery for rhegmatogenous retinal detachment with at least grade C PVR. The colored PFCL enabled retinal break examination and detection of residual intravitreal droplets in all surgeries. There was no case of separation or leakage of the dye from the PFCL solution that could have caused unwanted staining of the vitreous or epiretinal surface. CONCLUSION: The colored PFCL enabled intraoperative maneuvers such as endolaser use. In addition, removal of the colored PFCL was easily achieved at the end of surgery.

Colored perfluorocarbon liquids as novel intraoperative tools.

BACKGROUND: Perfluorocarbon liquids (PFCLs) are used as intraoperative tools to stabilize the retina during vitreoretinal surgeries. Their use would be much facilitated if PFCLs were colored and not transparent. We describe the development of a colored PFCL for vitreoretinal surgeries. METHODS: Perfluorohexyloctan (F6H8) was colored by adding a blue, biocompatible anthraquinone dye, and then mixed with perfluorodecalin (PFD) or perfluorooctane (PFO) at different volume percentages. The thus-obtained colored PFCLs were incubated with lens, lens capsule, vitreous body, and retina of enucleated porcine eyes for staining purpose and analyzed microscopically. To analyze possible interactions between colored PFCLs and silicone oil, colored PFCLs were exchanged to BSS and silicone oil respectively in enucleated pig eyes. RESULTS: By mixing different volume% of colored F6H8 with perfluorodecalin (PFD) or perfluorooctane (PFO), colored PFCLs of different density and staining intensity were obtained. Cornea, lens, lens capsule, vitreous, and retina showed no signs of staining after incubation with colored PFCLs for 10 min. Colored PFCLs were transparent despite intense coloring, thus allowing a clear visibility of the underlying tissue. Immediately after instillation of silicone oil, the colored PFCL bubble was well-defined, and colored PFCL was easily aspirated. After 5 minutes reaction time, considerable diffusion of the dye from the PFCL bubble into the silicone oil was observed. CONCLUSIONS: The staining intensity can be varied according to the volume% of the colored F6H8 phase. Colored PFCL is clearly visible when installed in the vitreous cavity of a pig eye, and can easily be removed. It does not stain the intraocular tissues in pig eyes. Colored PFCL can be exchanged with silicone oil. But a time-dependent diffusion of the dye into the silicone oil was observed in pig eyes, indicating that the contact should be limited.

Development of emulsification-resistant silicone oils: can we go beyond 2000 mPas silicone oil?

PURPOSE: To develop new blends of emulsification-resistant silicone oil based on high molecular weight (HMW) silicone oil for use as an endotamponade in vitreoretinal surgery. METHODS: Viscosity and elasticity of various silicone oil blends (Siluron 1000, Siluron 2000, Siluron 5000, 7% HMW + Siluron 1000, 10% HMW + Siluron 1000, and 15% HMW + Siluron 1000; Fluoron GmbH, Ulm, Germany) were measured using a piezoelectric axial vibrator. Emulsification was induced using a sonication device. Pluronic 10%, plasma, and serum were used as emulsifiers. The emulsion area was photographed and measured using ImageJ software (developed by Wayne Rasband, National Institutes of Health, Bethesda, MD; available at http://rsb.info.nih.gov/ij/index.html). RESULTS: Viscosity increased proportionally to HMW concentrations. Fluid elasticity was optimum using 10% HMW. Emulsification was at a minimum when using 10% or 15% HMW blends. CONCLUSIONS: A new silicone oil-based tamponade was developed with a viscosity similar to Siluron 5000 (at 37°C) but with significantly less emulsification tendency than Siluron 5000 or Siluron 2000. HMW concentration increases the fluid elasticity, thereby reducing the emulsification tendency.