Non-crosslinked Hyaluronic Acid Research Articles

Bipolar Radiofrequency and Non-Crosslinked Hyaluronic Acid Plus Calcium Hydroxyapatite in the Treatment of Stress Urinary Incontinence.

Stress urinary incontinence (SUI) causes both physical and psychological problems to women and their partners. Recently, vaginal radiofrequency (RF) application, as well as the administration of non-crosslinked hyaluronic acid (NCLHA) together with calcium hydroxyapatite (CaHA), has attracted attention for SUI treatment. The current, comparative study evaluated the efficacy and safety of these technologies acting separately and in a combined treatment. Sixty women with mild to moderate SUI, aged between 46 and 76 years (mean age 63.2) were divided into three groups intended for different treatments: group I, RF vaginal treatment only, group II, NCLHA plus CaHA periurethral injection only, group III, combined treatment including a single periurethral injection of NCLHA plus CaHA followed by four vaginal applications of RF at intervals of 3-5 days. The clinical effects of the treatments were evaluated by ICIQ-LUTSqol (Polish version) and UDI-6. The obtained results suggest that the symptoms of SUI and the quality of life of the patients improved significantly in each group after the therapies compared to the pre-treatment levels and were more persistent in the third HA + RF group compared to the HA or the RF group.

Combined Bipolar Radiofrequency and Non-Crosslinked Hyaluronic Acid Mesotherapy Protocol to Improve Skin Appearance and Epidermal Barrier Function: A Pilot Study.

Age-associated changes in epidermal hydration, pigmentation, thickness and cell renewal influence skin appearance and can lead to laxity, dryness and poor skin tone. The aim of this pilot study was to assess the synergistic effects of a new bipolar radiofrequency plus non-crosslinked hyaluronic acid (HA) mesotherapy protocol compared with radiofrequency alone on skin appearance and markers of epidermal function. This prospective, single-center, split-face pilot study recruited women aged 25-65 years with dryness and laxity of the facial skin defined by a trans-epidermal water loss (TEWL) value of ≥26 g/m2/h. Subjects were treated with a bipolar radiofrequency device on both sides of the face. This was immediately followed by needle hyaluronic acid (HA) treatment on one side of the face with 2.5 mL of a non-crosslinked HA. Photographic documentation, analysis of epidermal barrier function parameters, and high frequency (HF) ultrasound analysis were performed prior to treatment and at 28 days. Twenty female subjects with a mean age of 46 (range 29 to 54) years and dry and lax facial skin were included. TEWL was reduced and skin hydration improved to a greater extent with the combined radiofrequency plus mesotherapy protocol compared with radiofrequency alone (-5.8% vs. +3.9% and +23.1% vs. +1.0%, respectively). The combined protocol was also associated with greater improvements in melanin (-7.5% vs. -1.5%) and erythema values (-7.2% vs. +3.0%), respectively. Ultrasound measures of epidermal thickness and epidermal density were greater after the combined protocol compared with radiofrequency alone (12.0% vs. 5.6% and 57.7% vs. 7.1%, respectively). Both treatments were well-tolerated. The combined bipolar radiofrequency and HA mesotherapy protocol provided greater improvements in skin hydration, firmness and tone compared with radiofrequency alone. The combination treatment was also associated with greater epidermal thickness and density and increased keratinocyte differentiation suggesting a synergistic effect of both treatments on epidermal homeostasis and barrier function. Both treatments were well-tolerated and led to improvements in facial appearance.

Histopathologic analysis of hyaluronic acid composite solution following intravascular injection: Variability and safety.

Although a composite solution of non-crosslinked hyaluronic acid is generally considered safe, few studies have investigated its safety after intravascular injection. Male Sprague-Dawley rats were administered 0.05 mL of a non-crosslinked hyaluronic acid composite solution via intravascular injection into bilateral inferior epigastric arteries (IEA). Artery samples were obtained at multiple time points for histopathologic analysis. Bilateral abdominal flaps supplied by the IEA were lifted and the same dose of solution was injected into the artery, and flap survival was analyzed. Histopathologic analysis showed that the non-crosslinked hyaluronic acid composite solution remained temporarily in the artery lumen following intravascular injection. With continuous blood flow, the filler gradually disintegrated and the artery became recanalized. At 24 h, no filler remained in the lumen. At 7 days after the filler was injected into the IEA feeding the flap, there was no significant difference between the experimental and control groups with respect to flap survival rate. Non-crosslinked hyaluronic acid composite solution is relatively safe when a minimal volume is administered by intravascular injection. The filler will remain in the vessel for a short time, after which the vessel recanalizes.

Safety and performance assessment of hyaluronic acid-based vitreous substitutes in patients with phthisis bulbi.

To assess the safety and performance of hyaluronic acid-based vitreous substitutes in phthitic eyes. In this retrospective interventional study a total of 21 eyes from 21 patients with phthisis bulbi were treated at the Eye Clinic Sulzbach between August 2011 and June 2021. Patients who underwent a 23G pars plana vitrectomy received a vitreous substitute composed of (I) a non-crosslinked hyaluronic acid (Healon GV), (II) a crosslinked hyaluronic acid-based hydrogel (UVHA), or (III) silicone oil (SO-5000). Main outcome measures were the intraocular pressure (IOP), the visual acuity and the structural integrity of the retina and choroid assessed by optical coherence tomography. An increase in IOP ≥ 5 mmHg was achieved with SO-5000 in 5/8 eyes (6/10 interventions, 60.0%) for 36.4 ± 39.5 days, with Healon GV in 4/8 eyes (7/11 interventions, 63.6%) for 82.6 ± 92.5 days and with UVHA in 4/5 eyes (5/6 interventions, 83.3%) for 93.6 ± 92.5 days. Visual acuity increased in 5/21 eyes (23.8%), remained constant in 12/21 eyes (57.1%) and decreased in 4/21 eyes (19.0%). No enucleations were required during the mean follow-up time of 192 ± 182 days. The OCT images indicated the preservation of retinal structures, while choroidal folds were only diminished in UVHA eyes. Hyaluronic acid-based hydrogels are biocompatible vitreous substitutes in humans and can increase and stabilize IOP in patients with phthisis bulbi for about 3 months.

Lipid, Aqueous and Mucin Tear Film Layer Stability and Permanence within 0.15% Liposome Crosslinked Hyaluronic Acid versus 0.15% Non-Crosslinked Hyaluronic Acid Measured with a Novel Non-Invasive Ocular Surface Analyzer.

To evaluate the stability and permanence of the liquid film created after the instillation of 0.15% crosslinked hyaluronic acid with liposomes and crocin versus the effect of 0.15% standard hyaluronic acid, a prospective, longitudinal, single-blind, single-center study was conducted in symptomatic populations with a novel noninvasive ocular surface analyzer. Limbal and bulbar redness classification, lipid layer thickness, tear meniscus height, and first and mean noninvasive break-up time (FNIBUT and MNIBUT) were performed before and 30 and 45 min after liposome-crosslinked hyaluronic acid (LCHA) and standard hyaluronic acid (HA) eye drop instillations. LCHA had a higher lipid layer thickness than HA (grades 2.00 ± 0.83 and 1.17 ± 0.63 on the Guillon pattern, respectively). LCHA achieved a better tear meniscus height than HA (0.23 ± 0.02 and 0.21 ± 0.02 mm, respectively). LCHA improved FNIBUT and MNIBUT more than HA (for FNIBUT, 6.30 ± 0.94 and 4.77 ± 0.89 s, respectively. For MNIBUT, 17.23 ± 5.11 and 12.41 ± 4.18 s, respectively). Crosslinking hyaluronic acid with liposomes and crocin significantly increases the permanence and stability of the lipid, aqueous, and mucin tear film layers. In a short-term period, liposome and crosslinked hyaluronic acid achieved better first and mean noninvasive break-up times than standard hyaluronic acid.

Evaluating the influence of particle morphology and density on the viscosity and injectability of a novel long-acting local anesthetic suspension.

Proper pain management is well understood to be one of the fundamental aspects of a healthy postoperative recovery in conjunction with mobility and nutrition. Approximately, 10% of patients prescribed opioids after surgery continue to use opioids in the long-term and as little as 10days on opioids can result in addiction. In an effort to provide physicians with an alternative pain management technique, this work evaluates the material properties of a novel local anesthetic delivery system designed for controlled release of bupivacaine for 72 hours. The formulation utilizes solid-lipid microparticles that encapsulate the hydrophobic molecule bupivacaine in its free-base form. The lipid microparticles are suspended in a non-crosslinked hyaluronic acid hydrogel, which acts as the microparticle carrier. Two different particle manufacturing techniques, milling and hot homogenization, were evaluated in this work. The hot homogenized particles had a slower and more controlled release than the milled particles. Rheological techniques revealed that the suspension remains a viscoelastic fluid when loaded with either particle type up to 25% (w/v) particles densities. Furthermore, the shear thinning properties of the suspension media, hyaluronic acid hydrogel, were conserved when bupivacaine-loaded solid-lipid microparticles were loaded up to densities of 25% (w/v) particle loading. The force during injection was measured for suspension formulations with varying hyaluronic acid hydrogel concentrations, particle densities, particle types and particle sizes. The results indicate that the formulation viscosity is highly dependent on particle density, but hyaluronic acid hydrogel is required for lowering injection forces as well as minimizing clogging events.

In Vitro Hair Growth Promoting Effect of a Noncrosslinked Hyaluronic Acid in Human Dermal Papilla Cells.

Dermal papilla cells (DPCs) are a source of nutrients and growth factors, which support the proliferation and growth of keratinocytes as well as promoting the induction of new hair follicles and maintenance of hair growth. The protection from reactive oxygen species (ROS) and the promotion of angiogenesis are considered two of the basal mechanisms to preserve the growth of the hair follicle. In this study, a noncrosslinked hyaluronic acid (HA) filler (HYDRO DELUXE BIO, Matex Lab S.p.A.) containing several amino acids was tested with in vitro assays on human follicle dermal papilla cells (HFDPCs). The experiments were carried out to investigate the possible protection against oxidative stress and the ability to increase the vascular endothelial growth factor (VEGF) release. The results demonstrated the restoration of cell viability against UVB-induced cytotoxicity and an increase in the VEGF secretion. These data demonstrate the capability of the product to modulate human dermal papilla cells, suggesting a future use in mesotherapy, a minimally invasive local intradermal therapy (LIT), after further clinical investigations.

High-velocity pneumatic injection of non-crosslinked hyaluronic acid for skin regeneration and scar remodeling: A retrospective analysis of 115 patients.

Pneumatic-assisted high velocity jet injections are an alternative method for intradermal delivery of hyaluronic acid (HA) and demonstrated efficacy in dermal thickening and scar remodeling with minimal side effects. We aimed to investigate the clinical efficacy comparing non-crosslinked HA (NCL-HA) and crosslinked HA (CL-HA) for aesthetic skin concerns. We retrospectively analyzed charts of 115 patients treated with jet injected NCL-HA and CL-HA for skin rejuvenation, age-related laxity and rhytidosis, hypertrophic and acne scars and striae. Global Aesthetic Improvement Scale (GAIS) and the 5-grade patient satisfaction scale were used for assessment of the treatment efficacy at the 3-month follow-up. Efficacy was separately analyzed between patients receiving NCL-HA vs. CL-HA. Longevity of treatment effect was measured by the time to voluntary return for repeat treatment. An average of 2.8 treatments was completed per patient with a low incidence of side effects including bruises (7%) and temporary local edema (1%). Patients were highly-satisfied with the treatment results in all categories with the average satisfaction scores of 3.68 (NCL-HA) and 3.76 (CL-HA). An average GAIS score of 1.7 ("much improved") was calculated for neck, décolleté and perioral areas. An overall GAIS score averaged as 1.78 (NCL-HA) and 1.6 (CL-HA). Longevity of the effect averaged 13.1months for NCL-HA and 13.2months for CL-HA groups. Our retrospective data showed similar significant improvement of all aesthetic skin concerns in 115 subjects treated with either NCL-HA or CL-HA delivered intradermally by a high velocity jet-injector device with minimal downtime, pain or side-effects.

Combined autologous platelet‐rich plasma with microneedling versus microneedling with non‐cross‐linked hyaluronic acid in the treatment of atrophic acne scars: Split‐face study

Acne scarring causes cosmetic discomfort, depression, low self-esteem and reduced quality of life. Microneedling is an established treatment for scars. A multimodality approach to scar treatment is usually necessary to achieve the best cosmetic results. The objective of this study was to evaluate the efficacy and safety of platelet rich plasma (PRP) combined with microneedling in comparison with microneedling with non-cross-linked hyaluronic acid for the treatment of atrophic acne scars. Forty-one patients of 20-40 years of age with atrophic acne scars were included. Microneedling was performed on both halves of the face. Topical application of PRP was given on right half of the face, while the left half of the face was treated with topical application of non-cross-linked hyaluronic acid. Four treatment sessions were given at an interval of 1 month consecutively. Goodman's Qualitative scale and the quartile grading scale are used for the final evaluation of results. There was a statistically significant improvement in acne scars after treatment among the studied group. Right and left halves showed 85.4% and 82.9% improvement, So the difference of the improvement between the two modalities is statistically insignificant P > 0.05 We conclude that microneedling has efficacy in the management of atrophic acne scars. It can be combined with either PRP or noncross-linked hyaluronic acid to enhance the final clinical outcomes in comparison with microneedling alone. The difference between the two modalities is insignificant.

A pilot study on the use of a non-crosslinked hyaluronic acid with associated anti-oxidant ingredients to improve the effectiveness of Nd:YAG laser toning in the treatment of melasma in six patients.

Melasma is a common skin disorder. Nd:YAG laser toning is a popular treatment for melanin clearance. Treatment efficacy is limited by factors such as presence of reactive oxygen species, DNA damage, TEWL, and skin barrier disruption. The purpose of this pilot study is to explore the efficacy of a non-crosslinked hyaluronic acid with anti-oxidant ingredients in mitigating the above-stated factors in the treatment of melasma using Nd:YAG laser toning. In this pilot retrospective study of six cases with melasma, Nd:YAG laser toning was performed for each case until improvement of melasma has plateaued (after 4-6 sessions) and at which point treatment was paused. After injecting non-crosslinked hyaluronic acid (9-12mL) with anti-oxidant ingredients into the face with focus on the lesional skin, further sessions (4-6) of Nd:YAG laser toning was resumed. Before, interim (improvement has plateaued), and after (on completion of the remaining sessions of laser toning after hyaluronic acid injection) photos of the six cases were scored using modified MASI. ANOVA analysis was applied to the scores. All six melasma cases had further improvement in melasma clearance after hyaluronic acid injection beyond the point when improvement has plateaued. ANOVA analysis of before, interim, and after scores showed statistical significance in difference between the three groups. This pilot study of six cases suggests that the use of a non-crosslinked hyaluronic acid with anti-oxidants may improve the efficacy of Nd:YAG laser toning in the treatment of melasma.

Evaluation of safety and efficacy of booster injections of hyaluronic acid in improving the facial skin quality.

Skin boosting with small particles of hyaluronic acid (HA) is a new method of skin rejuvenation. Here, we aim to evaluate the efficacy and safety of booster injections of noncross-linked HA in improving the facial skin quality. A total of 20 men and women age 40.15±6.63years were treated with 3 injections of noncross-linked HA (1-2mL) with intervals of 3weeks. Skin hydration and elasticity parameters were evaluated before intervention and 1week and 4months later. Facial skin improvement also evaluated using physician's global assessment score (PGA). Skin hydration increased 1week and 4months after last treatment, (P>.05). Skin firmness (R0) reduced significantly at week 1 and month 4 (P-value=.01 and .00). Skin-tiring effect/fatigue (R3) showed significant decrease at week 1 and month 4 (P-value=.01 and .00, respectively). Four months after last treatment skin gross elasticity (R2) and net elasticity (R5) also increased significantly (P-value=.00). Physician's global assessment 1week and 4months after last treatment were 2.33±0.76 and 1.35±0.49 out of 4, respectively. Adverse effects were mostly transient and mild in severity. Booster therapy with HA is a safe and well-tolerated procedure, and results in improvement in skin elasticity and relative increase in skin hydration.

Comparison of the effects of polynucleotide and hyaluronic acid fillers on periocular rejuvenation: a randomized, double-blind, split-face trial

Background Filler injection has become an extremely popular method for facial skin rejuvenation, including the periorbital area. In the recent years, new polynucleotide (PN)-containing filler products have been used for esthetic purposes. Aim We aimed to investigate the efficacy and safety of PN filler injection in the periorbital area. Patients/methods A total of 27 subjects were enrolled in this randomized, pair-matched, and active-controlled study. Each subject received filler injections thrice with two-week intervals, with a PN filler injection on one side and a non-crosslinked hyaluronic acid (HA) filler injection on the contralateral side of the periorbital area. Results Improvements in the visual analog scale and global esthetic improvement scale scores were not significantly different between the PN and HA groups. The improvement rates of skin elasticity and hydration decreased over time in both groups, with the PN group showing a higher improvement rate. The improvement rates of roughness and pore volume were higher in the PN group than in the HA group. The improvement rate of dermal density was not significantly different between the groups. No serious adverse events were reported. Conclusion The PN filler injection is effective and safe for periorbital rejuvenation.

Improvements in Skin Quality Biological Markers in Skin Explants Using Hyaluronic Acid Filler VYC-12L.

Background:Hyaluronic acid (HA), both crosslinked and uncrosslinked, is used clinically to treat fine lines and provides additional improvements in skin quality attributes. The purpose of this study was to assess potential early differences in the expression of biological markers of skin quality in living human skin explants injected with uncrosslinked and crosslinked HA gels.Methods:Living human skin explants injected with VYC-12L or noncrosslinked HA with mannitol (HYD) and noninjected controls were assessed via microscopy, histology, and immunohistochemistry on days 3 and/or 8 for biological markers of elasticity (collagen density, elastin, fibrillin-1) and hydration [aquaporin-3, acidic glycosaminoglycans (GAGs), HA]. Hydration was also assessed via a corneometer probe on days 0, 1, 2, and 8.Results:On day 3 versus controls, VYC-12L moderately increased collagen density in the upper reticular dermis and clearly increased fibrillin-1 expression, with slight increases persisting on day 8. Increases with HYD were smaller and did not persist on day 8. Both VYC-12L and HYD increased aquaporin-3 expression and GAG content on days 3 and 8, but VYC-12L produced greater GAG increases in the reticular dermis. Day 8 instrument-assessed hydration increased by 49% and 22% for VYC-12L and HYD, respectively. Elastin expression in oxytalan and elaunin fibers was unchanged. Upper-dermal HA reductions suggested HA injection-induced hyaluronidase expression.Conclusion:VYC-12L produced greater, more lasting improvements in biological markers of skin quality than HYD.

The use of cellular matrix in symptomatic knee osteoarthritis.

Knee osteoarthritis is a degenerative “wear and tear” disorder affecting mainly population over 50 years old. It can also present in younger people, especially after an injury or as a part of other diseases. While many therapeutic options exist for knee osteoarthritis, none of them has the potential to cure this condition. Cellular Matrix represents a combination of natural non-crosslinked hyaluronic acid (HA), thixotropic cell separation gel, and sodium citrate anticoagulant solution. A combination of Cellular Matrix with autologous platelet-rich plasma (A-PRP) is a novel therapeutic approach to the management of knee osteoarthritis. It is assumed that the active components HA and PRP have a synergistic effect contributing to a better therapeutic outcome in patients with knee osteoarthritis. Physiotherapy could provide an additional benefit. This is a retrospective pilot study assessing the potential benefit of Cellular Matrix and A-PRP combined with physiotherapy in the management of chronic knee osteoarthritis. Twenty-five patients were enrolled in the study and injected with three doses of Cellular Matrix combined with A-PRP with a time span of 2 weeks between each injection. All patients received standardized physiotherapy. The results showed that 68% of patients achieved more than 50% improvement in pain, stiffness, and function of the knee joints. There were no adverse reactions. This retrospective pilot study confirmed the positive effect of PRP and HA combination in the management of mild and moderate knee osteoarthritis. These preliminary results need to be verified in randomized control trials.

IN VITRO DEGRADATION OF POLYDIOXANONE (PDO) LIFTING THREADS IN HYALURONIC ACID (HA).

Background: Recently, some clinicians have proposed implanting PDO threads imbibed in hyaluronic acid (HA). However, this is controversial since PDO sutures are hydrophilic and the presence of HA could increase the rate of hydrolysis. Aim: To demonstrate the degradation of PDO lifting threads in HA through ultramicroscopy. Materials and methods: Three, one cm long, segments of 23G PDO threads, where immersed in 1.5 ml non-crosslinked hyaluronic acid in previously labeled, sterile microcentrifuge tubes. These were observed by ultramicroscopy at 4x and 10x after 24, 48 and 72 hours. Results: Microphotographs taken after 24 hours already show structural changes in the fibers, presenting an increase in interlaminar spaces and dilution of violet pigmentation. At 48 hours, degradation continues. PDO hygroscopy is observed as aqueous content between the peripheral layers and the central core of the thread. Some fibers show breakage, and there is an increase in interlaminar and interfibrillar spaces. At 72 hours, as the pigment is released, larger empty spaces are observed in the central column of the thread, and there is disorganization of the peripheral fibrils with fraying all along the fiber. Conclusions: Hyaluronic acid induces rapid biodegradation of the PDO thread by hydrolysis beginning 24 hours after contact of the thread with the biomaterial. We hypothesize that non-crosslinked hyaluronic acid is a powerful catalyzing agent for hydrolytic degradation of the PDO thread, since this thread is highly hydrophilic. Thus, we suggest that clinically embedding PDO threads with HA will only accelerate biodegradation of the suture.
 Key words: Lifting threads, polydioxanone, hyaluronic acid, biodegradation, PDO hydrolysis

In Vitro Degradation of Polydioxanone Lifting Threads in Hyaluronic Acid.

Recently, some clinicians have proposed implanting polydioxanone (PDO) threads imbibed in hyaluronic acid (HA), arguing that this may reinforce the lifting effects. However, this is controversial because PDO sutures are hydrophilic and the presence of HA could increase the rate of hydrolysis. The aim of this study was to demonstrate the degradation of PDO lifting threads in HA through ultramicroscopy. It was a qualitative research and preclinical trial. Three, 1-cm-long, segments of 23-G PDO threads were immersed in 1.5-mL non-crosslinked HA in previously labeled, sterile microcentrifuge tubes. These were observed by ultramicroscopy at 4× and 10× after 24, 48, and 72 h. Microphotographs taken after 24 h show structural changes in the fibers, presenting an increase in interlaminar spaces and dilution of violet pigmentation. At 48 h, degradation continues. PDO hygroscopy is observed as aqueous content between the peripheral layers and the central core of the thread. At 72 h, as the pigment is released, larger empty spaces are observed in the central column of the thread, and there is disorganization of the peripheral fibrils with fraying all along the fiber. HA induces rapid biodegradation of the PDO thread by hydrolysis beginning 24 h after contact of the thread with the biomaterial. The non-crosslinked HA is a powerful catalyzing agent for hydrolytic degradation of the PDO thread, because this thread is highly hydrophilic. Clinically, embedding PDO threads in HA accelerates biodegradation of the suture.

Non-setting, injectable biomaterials containing particulate hydroxyapatite can increase primary stability of bone screws in cancellous bone

BackgroundFracture fixation in weak bone is still a clinical challenge. Screw augmentation was shown to successfully increase their primary stability. The currently used calcium phosphate or polymeric bone cements, however, present important drawbacks such as induced toxicity and/or impaired bone neo-formation. A new approach to enhance bone screw primary stability without affecting bone formation is the use of non-setting, calcium phosphate loaded soft materials as the augmentation material. MethodsTwo types of biomaterials (non-crosslinked hyaluronic acid as viscous fluid and agar as hydrogel) were loaded with 40 wt/vol% of hydroxyapatite particles and characterized. The screw augmentation effect of all materials was evaluated through pull-out tests in bovine cancellous bone and compared to the non-augmented situation (control). The bone mineral density of each test sample was measured with μCT scans and was used to normalize the pull-out strength. FindingsBoth materials loaded with hydroxyapatite increased the normalized pull-out strength of the screws compared to control samples and particle-free materials. This counter-intuitive augmentation effect increased with decreasing bone mineral density and was independent from the type of the soft materials used. InterpretationWe were able to demonstrate that non-setting, injectable biomaterials loaded with ceramic particles can significantly enhance the primary stability of bone screws. This material combination opens the unique possibility to achieve a screw augmentation effect without impairing or even potentially favoring the bone formation in proximity to the screw. This effect would be particularly advantageous for the treatment of osteoporotic bone fractures requiring a stabilization with bone screws.

Histomorphometric Comparison of Bone Regeneration in Critical-Sized Bone Defects Using Demineralized Bone Matrix, Platelet-Rich Fibrin, and Hyaluronic Acid as Bone Substitutes.

To compare bone regeneration in the critical-sized bone defects grafted with demineralized bone matrix, platelet-rich fibrin, and hyaluronic acid in rats. Forty Wistar Albino rats allocated into 4 experimental groups: platelet-rich fibrin (PRF) group, noncross-linked hyaluronic acid gel (HA) group, demineralized bone matrix in putty form (DBM) group, and control group. A critical-sized defect of 8 mm was formed involving the sagittal suture for each rat under anesthetic induction. All animals were sacrificed at 21st day after surgery and histomorphometric parameters of total horizontal length (THL) and total vertical length (TVL) of newly produced bone and longest bone trabecula (LBT) were measured in the histologic slides. The difference between experimental groups for these parameters was analyzed. There was statistically significant difference in THL and LBT but not in TVL. Total horizontal length was significantly increased in DBM group compared with control and HA groups (P < 0.05). There was also statistically significant increase in THL in PRF group compared with control group (P < 0.05). Longest bone trabecula significantly increased in DBM group compared with HA group (P < 0.05). There was also statistically significant increase in HA group compared with control group (P < 0.05) and LBT significantly increased in PRF group compared with HA group (P < 0.05). The sole usage of HA does not effectively increase bone regeneration when compared with DBM and PRF. The DBM and PRF do not have superiority to each other in the bone regeneration while they are superior to HA.

Effect of molecular weight of hyaluronic acid (HA) on viscoelasticity and particle texturing feel of HA dermal biphasic fillers.

BackgroundHyaluronic acid (HA) dermal biphasic fillers are synthesized for their efficacy in correcting aesthetic defects such as wrinkles, scars and facial contouring defects. The fillers consist of crosslinked HA microspheres suspended in a noncrosslinked HA. To extend the duration of HAs within the dermis and obtain the particle texturing feel, HAs are crosslinked to obtain the suitable mechanical properties.ResultsHyaluronic acid (HA) dermal biphasic fillers are prepared by mixing the crosslinked HA microspheres and the noncrosslinked HAs. The elastic modulus of the fillers increased with raising the volume fraction of the microspheres. The mechanical properties and the particle texturing feel of the fillers made from crosslinked HA (1058 kDa) microspheres suspended in noncrosslinked HA (1368 kDa) are successfully achieved, which are adequate for the fillers.ConclusionsDermal biphasic HA fillers made from 1058 kDa exhibit suitable elastic moduli (211 to 420 Pa) and particle texturing feel (scale 7 ~ 9).

In vitro study of RRS HA injectable mesotherapy/biorevitalization product on human skin fibroblasts and its clinical utilization.

Mesotherapy/biorevitalization with hyaluronic acid (HA) is a treatment approach currently used for skin rejuvenation. Various products with a wide range of polycomponent formulations are available on the market. Most of these formulations contain noncross-linked HA in combination with a biorevitalization cocktail, formed by various amounts of vitamins, minerals, amino acids, nucleotides, coenzymes, and antioxidants. Although ingredients are very similar among the different products, in vitro and clinical effects may vary substantially. There is a real need for better characterization of these products in terms of their action on human skin or in vitro skin models. In this study, we analyzed the effect of the RRS® (Repairs, Refills, Stimulates) HA injectable medical device on human skin fibroblasts in vitro. Skin fibroblast viability and its capacity to induce the production of key extracellular matrix were evaluated in the presence of different concentrations of RRS HA injectable. Viability was evaluated through colorimetric MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and key extracellular matrix genes, type I collagen and elastin, were quantified by quantitative polymerase chain reaction. Results demonstrated that RRS HA injectable could promote human skin fibroblast viability (+15%) and increase fibroblast gene expression of type I collagen and elastin by 9.7-fold and 14-fold in vitro, respectively. These results demonstrate that mesotherapy/biorevitalization products can, at least in vitro, effectively modulate human skin fibroblasts.