Rheologic and Physicochemical Characteristics of Hyaluronic Acid Fillers: Overview and Relationship to Product Performance.

Injections with hyaluronic acid (HA) fillers for facial rejuvenation and soft-tissue augmentation are among the most popular aesthetic procedures worldwide. Many HA fillers are available with unique manufacturing processes and distinct in vitro physicochemical and rheologic properties, which result in important differences in the fillers' clinical performance. The aim of this paper is to provide an overview of the properties most widely used to characterize HA fillers and to report their rheologic and physicochemical values obtained using standardized methodology to allow scientifically based comparisons. Understanding rheologic and physicochemical properties will guide clinicians in aligning HA characteristics to the facial area being treated for optimal clinical performance.

Evaluation of Physicochemical Properties Following Syringe-to-Syringe Mixing of Hyaluronic Acid Dermal Fillers.

BACKGROUND: Historically, soft-tissue hyaluronic acid (HA) fillers have been mixed with agents to reduce pain or alter physicochemical properties. OBJECTIVE: Evaluate the impact of dilution and mixing on HA filler physicochemical properties. MATERIALS AND METHODS: Crosslinked HA filler (VYC-20L, 20 mg/mL) was diluted to 15 mg/mL using saline through 5 or 10 passes between 2 syringes connected using a luer connector. Extrusion force, rheological properties, and microscopic appearance were assessed. Undiluted VYC-15L (15 mg/mL) served as the control. RESULTS: Average extrusion force was higher for diluted VYC-20L versus the control, with an increase in slope for gel diluted using 5 passes (0.65) and 10 passes (0.52) versus the control (<0.1). For diluted samples mixed with 5 or 10 passes, the rheological profile was different between the 2 halves of the syringe, with the second half more elastic than the first half, compared with the consistent profile of undiluted samples. Microscopically, diluted VYC-20L samples seemed more liquid near the luer and more particulate near the piston compared with the control, which was smooth throughout. CONCLUSION: In addition to potentially introducing contamination, diluting or mixing soft-tissue HA fillers yields a heterogeneous product with physicochemical characteristics that vary substantially throughout the syringe.

Basics of dermal filler rheology.

BACKGROUND: Hyaluronic acid injectable fillers are the most widely used dermal fillers to treat facial volume deficits, providing long-term facial aesthetic enhancement outcomes for the signs of aging and/or facial contouring. OBJECTIVES: The purpose of this article was to explain how rheology, the study of the flow of matter, can be used to help physicians differentiate between dermal fillers targeted to certain areas of the face. METHODS: This article describes how rheological properties affect performance when filler is used in various parts of the face and exposed to mechanical stress (shear deformation and compression/stretching forces) associated with daily facial animation and other commonly occurring external forces. RESULTS: Improving facial volume deficits with filler is linked mainly to gel viscoelasticity and cohesivity. These 2 properties set the level of resistance to lateral and vertical deformations of the filler and influence filler tissue integration through control of gel spreading. CONCLUSION: Selection of dermal filler with the right rheological properties is a key factor in achieving a natural-looking long-lasting desired aesthetic outcome.

Rheological Properties and In Vivo Performance Characteristics of Soft Tissue Fillers.

BACKGROUND: Physicochemical properties and performance in nonclinical animal models can provide insights into soft tissue filler performance. OBJECTIVE: To evaluate the in vivo performance of fillers with different compositions and physicochemical properties. MATERIALS AND METHODS: Physicochemical properties were measured in vitro. Rat models were developed and used to compare lift capacity, resistance to deformation, and tissue integration. Four homogeneous hyaluronic acid (HA) fillers, 2 nonanimal stabilized HA (NASHA) fillers, and 1 calcium hydroxylapatite/carboxymethyl cellulose (CaHA/CMC) filler were evaluated. RESULTS: Filler lift capacity correlated better with filler composition/type (homogeneous > NASHA > CaHA/CMC) than with specific rheological properties. The CaHA/CMC filler had high initial resistance to deformation relative to other groups; all HA fillers exhibited lower initial resistance to deformation, which increased over time. Homogeneous HA fillers were integrated with surrounding tissue, whereas integration within particle-based fillers (NASHA and CaHA/CMC) was variable, with some areas void of tissue. CONCLUSION: The animal models provide a platform to make comparative evaluations among fillers. The results indicated that biological interaction plays an important role in how the filler performs. Rheology alone was not sufficient to understand filler performance but was most useful when comparing within fillers of similar composition.

Preventing biofilm formation and associated occlusion by biomimetic glycocalyxlike polymer in central venous catheters.

The use of catheters and other implanted devices is constantly increasing in modern medicine. Although catheters improve patients' healthcare, the hydrophobic nature of their surface material promotes protein adsorption and cell adhesion. Catheters are therefore prone to complications, such as colonization by bacterial and fungal biofilms, associated infections, and thrombosis. Here we describe the in vivo efficacy of biologically inspired glycocalyxlike antiadhesive coatings to inhibit Staphylococcus aureus and Pseudomonas aeruginosa colonization on commercial totally implantable venous access ports (TIVAPs) in a clinically relevant rat model of biofilm infection. Although noncoated TIVAPs implanted in rats were heavily colonized by the 2 biofilm-forming pathogens with a high percentage of occlusion, coating TIVAPs reduced their initial adherence and subsequently led to 4-log reduction in biofilm formation and reduced occlusion. Our antiadhesive approach is a simple and generalizable strategy that could be used to minimize clinical complications associated with the use of implantable medical devices.

Luminescence of polyethylene glycol coated CdSeTe/ZnS and InP/ZnS nanoparticles in the presence of copper cations.

The use of click chemistry for quantum dot (QD) functionalization could be very promising for the development of bioconjugates dedicated to in vivo applications. Alkyne-azide ligation usually requires copper(I) catalysis. The luminescence response of CdSeTe/ZnS nanoparticles coated with polyethylene glycol (PEG) is studied in the presence of copper cations, and compared to that of InP/ZnS QDs coated with mercaptoundecanoic acid (MUA). The quenching mechanisms appear different. Luminescence quenching occurs without any wavelength shift in the absorption and emission spectra for the CdSeTe/ZnS/PEG nanocrystals. In this case, the presence of copper in the ZnS shell is evidenced by energy-filtered transmission electron microscopy (EF-TEM). By contrast, in the case of InP/ZnS/MUA nanocrystals, a redshift of the excitation and emission spectra, accompanied by an increase in absorbance and a decrease in photoluminescence, is observed. For CdSeTe/ZnS/PEG nanocrystals, PL quenching is enhanced for QDs with 1) smaller inorganic-core diameter, 2) thinner PEG shell, and 3) hydroxyl terminal groups. Whereas copper-induced PL quenching can be interesting for the design of sensitive cation sensors, copper-free click reactions should be used for the efficient functionalization of nanocrystals dedicated to bioapplications, in order to achieve highly luminescent QD bioconjugates.

Copper-free click chemistry for highly luminescent quantum dot conjugates: application to in vivo metabolic imaging.

Quantum dots (QD) are inorganic nanocrystals with outstanding optical properties, specially suited for biological imaging applications. Their attachment to biomolecules in mild aqueous conditions for the design of bioconjugates is therefore highly desirable. 1,3-dipolar [3 + 2] cycloaddition between azides and terminal alkynes ("click chemistry") could represent an attractive QD functionalization method. Unfortunately, the use of the popular Cu(I)-catalyzed version of this reaction is not applicable for achieving this goal, since the presence of copper dramatically alters the luminescence properties of QD dispersions. We demonstrate here that copper-free click chemistry, between strained cyclooctyne functionalized QD and azido-biomolecules, leads to highly luminescent conjugates. In addition, we show that QD-cyclooctyne can be used at previously unreported low concentration (250 nM) for imaging the incorporation of azido-modified sialic acid in cell membrane glycoproteins.

Novel water-soluble near-infrared cyanine dyes: synthesis, spectral properties, and use in the preparation of internally quenched fluorescent probes.

In this paper, we describe the synthesis and the photophysical properties of two novel near-infrared (NIR) cyanine dyes (NIR5.5-2 and NIR7.0-2) which are water soluble potential substitutes of the commercially available Cy 5.5 and Cy 7.0 fluorescent labels respectively. For each one of these cyanine dyes, the synthetic strategy relies on the postsynthetic derivatization of a cyanine precursor in order to introduce the key functionalities required for bioconjugation of these NIR fluorophores. For NIR5.5-2, a reactive amino group was acylated with an original trisulfonated linker for water solubility. For NIR7.0-2, a vinylic chlorine atom was derivatized through a SRN1 reaction for the introduction of a monoreactive carboxyl group for labeling purposes. Unexpectedly, when these two fluorophores were closely associated within a peptidic architecture, mutual fluorescence quenching between NIR5.5-2 and NIR7.0-2 was observed both at 705 (NIR5.5-2) and 798 nm (NIR7.0-2). On the basis of this property, a novel internally quenched caspase-3-sensitive NIR fluorescent probe was prepared.