Hyaluronic Acid Fragments Research Articles

A closed-loop patch based on bioinspired infection sensor for wound management

Pathogenic wound infections remain a major global health challenge. When skin tissue is wounded, some colonizing pathogenic bacteria secrete large amounts of hyaluronidase (HAase) to degrade the extracellular matrix (ECM), enabling their diffusion and proliferation. Current clinical techniques for detecting infection rely on basic visual cues or analysis of wound fluids, enabling only reactive treatment once severe signs manifest. Herein, we present the use of a closed-loop patch (CLP) for advanced wound management. The patch contains a bio-inspired sensor based on an engineered hyaluronic acid (HA) hydrogel that detects HAase secreted by invading pathogens. This detection triggers a quantifiable change in the capacitance of the interdigital electrode and achieving in-time detection of Staphylococcus aureus (S. aureus) infection in a murine wound model before obvious visual signs appear. In response, the release of titanium hydride (TiH1.924) nanodots from hydrogel decomposition can eradicate pathogens under ultrasound (US) irradiation. Concurrently, the product, HA fragments further promoted cell migration and angiogenesis to significantly improve wound healing by ∼14.6-fold rates in 12 days. Overall, the CLP provides a sensory act-treat effect according to the wound status, which facilitate the closed-loop integration of monitoring and rehabilitation. This strategy may provide additional possibilities for the design of future wound management systems.

The efficacy of hyaluronic acid fragments with amino acid in combating facial skin aging: an ultrasound and histological study

BackgroundVarious techniques have been employed in aesthetic medicine to combat skin aging, in particular that of the facial region. Hyaluronic acid is utilized to enhance moisture levels and extracellular matrix molecules. This study aims to histologically assess the effects of low molecular weight hyaluronic acid fragments combined with amino acids (HAAM) on facial skin rejuvenation through intradermal microinjections.MethodsA total of twenty women, with an average age of 45 and ranging from 35 to 64 years old, participated in the study, including 8 in menopause and 12 in the childbearing age group. Mesotherapy was used to administer HAAM to the patients. Prior to and three months after the treatment, each patient underwent small circular punch biopsies. Ultrasound examinations were conducted using B-mode, capturing 2D images in longitudinal or transverse orientations with frequencies ranging from 5 to 13 Mega-hertz (MY LAB X8, ESAOTE, Genova, Italy). A total of 60 ultrasound examinations were taken, with 30 collected before treatment and 30 after treatment.ResultsThe histological analysis demonstrates an increase in fibroblast activity resulting in the production of Type III reticular collagen, as well as an increased number of blood vessels and epidermal thickness. However, the analysis of ultrasound data before and after treatment showed no statistical difference in skin thickness in malar area, chin and mandibular angle.ConclusionsHistological assessments indicate that subcutaneous infiltration of HAAM has a substantial impact on the dermis of facial skin.

The bioengineering application of hyaluronic acid in tissue regeneration and repair

The multifaceted role of hyaluronic acid (HA) across diverse biomedical disciplines underscores its versatility in tissue regeneration and repair. HA hydrogels employ different crosslinking including chemical (chitosan, collagen), photo- initiation (riboflavin, LAP), enzymatic (HRP/H2O2), and physical interactions (hydrogen bonds, metal coordination). In biophysics and biochemistry, HA's signaling pathways, primarily through CD44 and RHAMM receptors, modulate cell behavior (cell migration; internalization of HA), inflammation, and wound healing. Particularly, smaller HA fragments stimulate inflammatory responses through toll-like receptors, impacting macrophages and cytokine expression. HA's implications in oncology highlight its involvement in tumor progression, metastasis, and treatment. Elevated HA in tumor stroma impacts apoptosis resistance and promotes tumor growth, presenting potential therapeutic targets to halt tumor progression. In orthopedics, HA's presence in synovial fluid aids in osteoarthritis management, as its supplementation alleviates pain, enhances synovial fluid's viscoelastic properties, and promotes cartilage integrity. In ophthalmology, HA's application in dry eye syndrome addresses symptoms by moisturizing the eyes, replenishing tear film deficiencies, and facilitating wound healing. Intravitreal injections and hydrogel-based systems offer versatile approaches for drug delivery and vitreous humor replacement. For skin regeneration and wound healing, HA hydrogel dressings exhibit exceptional properties by promoting moist wound healing and facilitating tissue repair. Integration of advanced regenerative tools like stem cells and solubilized amnion membranes into HA-based systems accelerates wound closure and tissue recovery. Overall, HA's unique properties and interactions render it a promising candidate across diverse biomedical domains, showcasing immense potentials in tissue regeneration and therapeutic interventions. Nevertheless, many detailed cellular and molecular mechanisms of HA and its applications remain unexplored and warrant further investigation.

Increased level of C3 in synovial fluid in patients with activated osteoarthritis as a diagnostic and therapeutic target – pilot group of patients from the Rheumatology Department at UMHAT Burgas

The clinical course of osteoarthritis (OA) indicates the role of low-grade synovitis as the main driver of the degenerative process. Components of the extracellular matrix, fibronectin isoforms, and fragments of hyaluronic acid are presumed ligands for DAMPs (particularly TLR). Complement fractions bind to the corresponding receptors on the cell membranes of chondrocytes and synoviocytes through TLR. Does the complement cascade play a role only as a clearing system and/or a leading pathogenetic factor in activated OA? The aim of this study is to answer this question. The study included 50 patients with activated OA of the knee joint. We examined the levels of C3 and C4 complement fractions in the blood plasma and synovial fluid. We found that the values of these proteins in synovial fluid were on average 34.90% for C3 and 30.97% for C4 of their values in blood plasma, with a generally accepted norm of 10% for complement levels in a healthy joint. The observation regarding the strength of correlation between the above results and the radiological stage confirmed a stronger correlation of the obtained results in the earlier stages of the disease when the activity of the repair processes is more pronounced. In this way, we objectified the pathogenetic role of complement in the arthritic process, as well as its role in clearing the joint space from degradation products. The question arises whether pharmacological intervention to balance complement activation could represent a future therapeutic strategy in the treatment of OA and prevent its progression.

Functional divergence of a bacterial enzyme promotes healthy or acneic skin

Acne is a dermatologic disease with a strong pathologic association with human commensal Cutibacterium acnes. Conspicuously, certain C. acnes phylotypes are associated with acne, whereas others are associated with healthy skin. Here we investigate if the evolution of a C. acnes enzyme contributes to health or acne. Two hyaluronidase variants exclusively expressed by C. acnes strains, HylA and HylB, demonstrate remarkable clinical correlation with acne or health. We show that HylA is strongly pro-inflammatory, and HylB is modestly anti-inflammatory in a murine (female) acne model. Structural and phylogenic studies suggest that the enzymes evolved from a common hyaluronidase that acquired distinct enzymatic activity. Health-associated HylB degrades hyaluronic acid (HA) exclusively to HA disaccharides leading to reduced inflammation, whereas HylA generates large-sized HA fragments that drive robust TLR2-dependent pathology. Replacing an amino acid, Serine to Glycine near the HylA catalytic site enhances the enzymatic activity of HylA and produces an HA degradation pattern intermediate to HylA and HylB. Selective targeting of HylA using peptide vaccine or inhibitors alleviates acne pathology. We suggest that the functional divergence of HylA and HylB is a major driving force behind C. acnes health- and acne- phenotype and propose targeting of HylA as an approach for acne therapy.

Low, medium, and high molecular weight hyaluronic acid effects on human dental pulp stem cells in vitro

Hyaluronic acid (HA), an extracellular biopolymer found throughout the human body, holds promise as a biocompatible and biodegradable scaffold material. High molecular weight (HMW) HA degrades, generating low molecular weight (LMW) fragments with distinct properties. These fragments can influence the behaviour of cells, including human dental pulp stem cells (hDPSCs) incorporated into HA-containing hydrogels or scaffolds. Therefore, a comprehensive examination of the impact of a range of HA molecular weights on hDPSCs is essential before designing HA-based scaffolds for these cells. hDPSC lines were cultured with LMW HA (800 Da, 1600 Da, 15 kDa), medium molecular weight HA (237 kDa), or HMW HA (1500 kDa) over six passages. The various molecular weights had negligible effects on hDPSCs viability, morphology, adhesion, or relative telomere length. Furthermore, the expression of key surface stemness markers (CD29, CD44, CD73, CD90) remained unaltered. HA did not induce osteogenic, chondrogenic, or adipogenic differentiation. Moreover, the potential for chondrogenic and osteogenic differentiation was not adversely affected by LMW or HMW HA. Various molecular weights of HA seem safe, biocompatible and therefore suitable components for hDPSCs-containing scaffolds. These findings affirm that the hDPCSs will not be negatively affected by HA fragments resulting from scaffold degradation.

Investigation of Crosslinking Parameters and Characterization of Hyaluronic Acid Dermal Fillers: From Design to Product Performances.

Despite process similarities, distinctive manufacturing technologies offer hyaluronic acid dermal fillers with different in vitro physicochemical and rheological properties due to peculiar crosslinked hydrogel networks. A better understanding of dermal filler properties could provide specific clinical indications and expectations with more accurate performance correlations. In this study, with an emphasis on the degree of modification, hyaluronic acid concentration and molecular weight, these process parameters were able to modulate dermal filler properties, especially rheology. Moreover, an extensive characterization of commercial hyaluronic acid injectables of the Hyal System line was described to present product properties and help to elucidate related clinical effects. Standardized methodologies were applied to correlate in vitro parameters with feasible clinical indications. In view of an optimized dermal filler design, the results of the extrudability measurements allowed the quantification of the effect of hydrogel composition, rheological properties and needle size on injectability. Composition, dynamic viscosity and needle size showed an impactful influence on hydrogel extrudability. Finally, the positive influence of 200 KDa hyaluronic acid in comparison to fragments of ether-crosslinked hyaluronic acid on fibroblast recognition were shown with a migration assay.

Quantum Molecular Resonance Inhibits NLRP3 Inflammasome/Nitrosative Stress and Promotes M1 to M2 Macrophage Polarization: Potential Therapeutic Effect in Osteoarthritis Model In Vitro.

This study aimed to investigate the anti-inflammatory effects of Quantum Molecular Resonance (QMR) technology in an in vitro model of osteoarthritis-related inflammation. The study used THP-1-derived macrophages stimulated with lipopolysaccharide and hyaluronic acid fragments to induce the expression of inflammatory cytokines and nitrosative stress. QMR treatment inhibited COX-2 and iNOS protein expression and activity and reduced NF-κB activity. Furthermore, QMR treatment led to a significant reduction in peroxynitrite levels, reactive nitrogen species that can form during inflammatory conditions, and restored tyrosine nitration values to those similar to sham-exposed control cells. We also investigated the effect of QMR treatment on inflammasome activation and macrophage polarization in THP-1-derived macrophages. Results showed that QMR treatment significantly decreased NLRP3 and activated caspase-1 protein expression levels and downregulated IL-18 and IL-1β protein expression and secretion. Finally, our findings indicate that QMR treatment induces a switch in macrophage polarization from the M1 phenotype to the M2 phenotype.

Complement protein C1q stimulates hyaluronic acid degradation via gC1qR/HABP1/p32 in malignant pleural mesothelioma.

Complement component C1q can act as a pro-tumorigenic factor in the tumor microenvironment (TME). The TME in malignant pleural mesothelioma (MPM) is rich in C1q and hyaluronic acid (HA), whose interaction enhances adhesion, migration and proliferation of malignant cells. HA-bound C1q is also capable of modulating HA synthesis. Thus, we investigated whether HA-C1q interaction would affect HA degradation, analyzing the main degradation enzymes, hyaluronidase (HYAL)1 and HYAL2, and a C1q receptor candidate. We first proceeded with the characterization of HYALs in MPM cells, especially HYAL2, since bioinformatics survival analysis revealed that higher HYAL2 mRNA levels have an unfavorable prognostic index in MPM patients. Interestingly, Real-Time quantitative PCR, flow cytometry and Western blot highlighted an upregulation of HYAL2 after seeding of primary MPM cells onto HA-bound C1q. In an attempt to unveil the receptors potentially involved in HA-C1q signaling, a striking co-localization between HYAL2 and globular C1q receptor/HABP1/p32 (gC1qR) was found by immunofluorescence, surface biotinylation and proximity ligation assays. RNA interference experiments revealed a potentially regulatory function exerted by gC1qR on HYAL2 expression, since C1QBP (gene for gC1qR) silencing unexpectedly caused HYAL2 downregulation. In addition, the functional blockage of gC1qR by a specific antibody hindered HA-C1q signaling and prevented HYAL2 upregulation. Thus, C1q-HA interplay is responsible for enhanced HYAL2 expression, suggesting an increased rate of HA catabolism and the release of pro-inflammatory and pro-tumorigenic HA fragments in the MPM TME. Our data support the notion of an overall tumor-promoting property of C1q. Moreover, the overlapping localization and physical interaction between HYAL2 and gC1qR suggests a potential regulatory effect of gC1qR within a putative HA-C1q macromolecular complex.

Upregulation of tight junction-related proteins by hyaluronic acid in human HaCaT keratinocytes

Hyaluronic acid (HA) is a natural polysaccharide widely used in dermatology; however, HA effects on the expression of proteins related to skin barrier function and their dependence on the HA molecular weight are still limited. In this study, we treated immortalized human keratinocytes with HA samples of low and high molecular weights (LMW-HA, <100 kDa and HMW-HA, >500 kDa, respectively) and analyzed the expression of tight junction-forming proteins. Both LMW-HA and HMW-HA significantly increased the expression of claudin-3 and claudin-4, whereas HMW-HA also upregulated junctional adhesion molecule JAM-1. These results indicate that HA could improve the skin barrier function by inducing the expression of tight junction-related genes in keratinocytes and that the effect could depend on the molecular weight of HA fragments.

Abstract 5020: IRAK1 is a critical mediator of hyaluronic acid induced stemness

Abstract Ovarian cancer (OvCa) is the leading cause of gynecologic cancer-related deaths, due in part to late-stage diagnoses. While the overall response rate to first line therapy is encouraging (~80%), the majority of women develop recurrent disease, characterized by resistance to standard chemotherapy. There is convincing evidence that cancer stem cells (CSCs) have implications in resistance and recurrence of OvCa. To understand the pathways involved in enhancing this stem-like phenotype, we performed RNA sequencing and identified TLR-ILR1 (TIR) pathways as highly activated in cisplatin resistant OvCa and stem-cell populations. Subsequently, using a tumor microarray, we observed that interleukin receptor-associated kinase 1 (IRAK1), a critical mediator of TIR signaling, is upregulated in OvCa patient tissues compared to normal. This expression further correlated with younger diagnosis age and shorter overall survival, suggesting a role in OvCa tumorigenesis. Knockdown of IRAK1 by specific shRNA in OvCa cells, significantly impaired CSC enriched spheroid growth and orthotopic tumor growth in mouse models replicating advanced peritoneal OvCa. RNA sequencing of IRAK1 knocked down cells identified downregulation of CSC related genes including STAT3, MYC, NOTCH1, and NOTCH3. In addition, there was a reduction in the cisplatin efflux transporter ABCC1 and stemness marker gene CD44. Advanced OvCa is often associated (~90% in stage III and IV) with the development of malignant ascites. We demonstrate for the first time that significant amounts of low molecular weight hyaluronic acid fragments (LMW HA) are present in ascites. LMW HA induced IRAK1 dependent activation of non-canonical signaling through PKC-β leading to induction of STAT3 phosphorylation and MYC. This was further accompanied by increased spheroid formation, demonstrating a critical role for IRAK1 in HA-induced stemness. We have further identified a selective IRAK1 inhibitor, TCS2210 (1,2-Dihydro-N-hydroxy-2-oxo-3-(3-phenylpropyl)-6-quinoxalinecarboxamide). TCS2210 abrogated LMW HA induced activation of IRAK1 and expression of stemness genes MYC, NOTCH1, and NOTCH3. Lastly, we found that TCS2210 effectively suppresses OvCa cell growth in vitro and in vivo, synergizing with standard-of-care cisplatin. Our data suggests a role of IRAK1 in OvCa, by enhancing cancer cell growth and stemness. It further suggests that IRAK1 is a putative target for advanced OvCa. Citation Format: David Standing, Prasad Dandawate, Jaimie Johnson, Sumedha Gunewardena, Michele T. Pritchard, Harsh Pathak, Dineo Khabele, Katherine Roby, Andrew Godwin, Roy Jensen, Scott Weir, Shrikant Anant. IRAK1 is a critical mediator of hyaluronic acid induced stemness. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5020.

Anti-Inflammatory Effects of the 35kDa Hyaluronic Acid Fragment (B-HA/HA35).

Hyaluronic acid (HA) and HA fragments interact with a variety of human body receptors and are involved in the regulation of various physiological functions and leukocyte trafficking in the body. Accordingly, the development of an injectable HA fragment with good tissue permeability, the identification of its indications, and molecular mechanisms are of great significance for its clinical application. The previous studies showed that the clinical effects of injectable 35kDa B-HA result from B-HA binding to multiple receptors in different cells, tissues, and organs. This study lays the foundation for further studies on the comprehensive clinical effects of injectable B-HA. We elaborated on the production process, bioactivity assay, efficacy analyses, and safety evaluation of an injectable novel HA fragment with an average molecular weight of 35 kDa (35 kDa B-HA), produced by recombinant human hyaluronidase PH20 digestion. The results showed that 35 kDa B-HA induced human erythrocyte aggregation (rouleaux formation) and accelerated erythrocyte sedimentation rates through the CD44 receptor. B-HA application and injection treatment significantly promoted the removal of mononuclear cells from the site of inflammation and into the lymphatic circulation. At a low concentration, 35 kDa B-HA inhibited production of reactive oxygen species and tumor necrosis factor by neutrophils; at a higher concentration, 35 kDa B-HA promoted the migration of monocytes. Furthermore, 35 kDa B-HA significantly inhibited the migration of neutrophils with or without lipopolysaccharide treatment, suggesting that in local tissues, higher concentrations of 35 kDa B-HA have antiinflammatory effects. After 99mTc radiolabeled 35 kDa B-HA was intravenously injected into mice, it quickly entered into the spleen, liver, lungs, kidneys and other organs through the blood circulation. This study demonstrated that the HA fragment B-HA has good tissue permeability and antiinflammatory effects, laying a theoretical foundation for further clinical studies.

Injectable cell-targeting fiber rods to promote lipolysis and regulate inflammation for obesity treatment.

Obesity has become a worldwide public health problem and continues to be one of the leading causes of chronic diseases. Obesity treatment is challenged by large drug doses, high administration frequencies and severe side effects. Herein, we propose an antiobesity strategy through the local administration of HaRChr fiber rods loaded with chrysin and grafted with hyaluronic acid and AtsFRk fiber fragments loaded with raspberry ketone and grafted with adipocyte target sequences (ATSs). The hyaluronic acid grafts double the uptake levels of HaRChr by M1 macrophages to promote phenotype transformation from M1 to M2 through upregulating CD206 and downregulating CD86 expressions. ATS-mediated targeting and sustained release of raspberry ketone from AtsFRk increase the secretion of glycerol and adiponectin, and Oil red O staining shows much fewer lipid droplets in adipocytes. The combination treatment with AtsFRk and the conditioned media from HaRChr-treated macrophages elevates adiponectin levels, suggesting that M2 macrophages may secrete anti-inflammatory factors to stimulate adipocytes to produce adiponectin. Diet-induced obese mice showed significant weight losses of inguinal (49.7%) and epididymal (32.5%) adipose tissues after HaRChr/AtsFRk treatment, but no effect was observed on food intake. HaRChr/AtsFRk treatment reduces adipocyte volumes, lowers serum levels of triglycerides and total cholesterol and restores adiponectin levels to those of normal mice. In the meantime, HaRChr/AtsFRk treatment significantly elevates the gene expression of adiponectin and interleukin-10 and downregulates tissue necrosis factor-α expression in the inguinal adipose tissues. Thus, local injection of cell-targeting fiber rods and fragments demonstrates a feasible and effective antiobesity strategy through improving lipid metabolism and normalizing the inflammatory microenvironment.

Synthesis of Oligosaccharides Structurally Related to Hyaluronic Acid Fragments

Synthesis of Oligosaccharides Structurally Related to Hyaluronic Acid Fragments

Adsorption/desorption behavior of hyaluronic acid fragments at charged hydrophobic surface

This work reveals the growing potential of novel electrochemical methods that are applicable for polysaccharides. It was shown for the first time that the molecules of hyaluronic acid (HA) exhibit electrochemical response using phase-sensitive alternating current (AC) voltammetry in phase-out mode. Adsorption and desorption processes of HA fragments at a charged interface of mercury electrode were observed in buffered HA solutions. Electrostatic and hydrophobic manners of interactions were distinguished for native hyaluronan fragments in a wide electric potential range. The AC voltammetry response depended on the temperature, concentration, and length of HA chains. Results of this work open possibilities for further structural characterization of widely used HA fragments and understanding manners of interactions with charged hydrophobic surfaces that could be useful in the future for understanding HA interactions at biological levels.

FOLLICULAR FLUID HYALURONIC ACID POLYDISPERSITY IS ASSOCIATED WITH AGE AND IN VITRO FERTILIZATION CYCLE OUTCOME: A PILOT STUDY

Human follicular fluid is rich with Hyaluronic acid (HA). HA is synthesized as a high-molecular weight (HMW) linear disaccharide polymer. It is fragmented into low-molecular weight (LMW) HA by the activity of hyaluronidases and reactive oxygen species. HA size determines its biological function: HMW HA (>1000kDa) displays anti-inflammatory and immunosuppressive properties, and LMW HA (generally <500kDa) can induce the release of pro-inflammatory cytokines. Our group has previously demonstrated that LMW HA fragments compromise estradiol production and gamete quality of mouse follicles, in vitro.

28073 Evaluation of the impact of hyaluronic acid (HA) filler manufacturing technologies on HA chain degradation

Introduction: Hyaluronic acid (HA) chains readily degrade under crosslinking conditions employed to stabilize HA for aesthetic use. Different manufacturing technologies result in fillers that significantly vary in HA chain integrity, which may impact clinical performance and safety of products in situ. HA fragments generated during the manufacturing process are extractable as a soluble HA (sHA) fraction. This study examined sHA chain length and distribution in commercial filler products to understand the impact of filler manufacturing technologies on HA chain degradation.

Hyaluronic acid (HA) stimulates the in vitro expression of CD44 proteins but not HAS1 proteins in normal human epidermal keratinocytes (NHEKs) and is HA molecular weight dependent.

In the skin, hyaluronic acid is broken down to smaller fragments by hyaluronidase enzymes, particularly when skin is wounded. The impact of various molecular weight fragments of HA on normal human epidermal keratinocytes (NHEK) with regard to expression of important cellular proteins has not been deeply explored. Examination of three molecular weight (Mw) fractions of hyaluronic acid: 1) average Mw of the high fraction: 1.5-2MDa, 2) average Mw of the medium fraction: 200-500kDa, and 3) average Mw of the low fraction: 5-10kDa and a unique 1:1:1 composite complex of the three HA fragments (Triluronic® Acid) was done to examine the influence of the HA on two critical skin cell protein targets: hyaluronan synthase-1 (HAS-1) and the HA binding protein cluster of differentiation 44 (CD44). NHEKs were treated in vitro with a 1.0% stock solution of each HA Mw fraction at 1.0, 0.5, and 0.1% concentrations of the 1.0% solution and the polysaccharide composite at the same concentrations for 48 Hrs. The cells were than analyzed by ELISA protein assays for HAS-1 and CD44 protein content. Examination of HAS-1 protein expression indicates that none of the HA test materials influenced the expression of HAS-1 at any concentration. Examination of the CD44 protein expression indicated that the low Mw fraction and the commercial complex of the three Mw fractions upregulated CD44 protein expression in NHEKs, but the medium Mw and high Mw HA fractions did not. In this work, it was demonstrated that HA can influence the expression of CD44 protein, a critical HA transmembrane HA binding protein, and the influence appears to be molecular weight dependent.

Advanced Concepts in Rheology for the Evaluation of Hyaluronic Acid-Based Soft Tissue Fillers.

Crosslinked hyaluronic acid (HA)-based soft tissue fillers possess unique viscoelastic properties intended to match specific product indications. Manufacturing has an impact on HA chain integrity and on filler properties. This study introduces 2 new rheological parameters to evaluate the macroscopic characteristics of fillers. A library of reference commercialized HA fillers was selected to cover the full spectrum of product indications. Gels were assessed in terms of size of released HA fragments as a readout of gel integrity, degree of modification, cohesivity, and rheological properties. The elastic modulus G' often used to characterize fillers was shown not to follow macroscopic mechanical properties. To improve the mechanical characterization of fillers, Strength and Stretch scores were developed and tested. The Strength score defined the ability of a filler to sustain constant viscoelasticity over a wide range of constraints and represented the filler mechanical resilience. The Stretch score measured the propensity of a filler to deform in view to improve implant adaptation to facial animation for natural-looking results. Strength and Stretch scores sorted rheological parameters to macroscopic cohesivity assays more accurately than G' and may thus help predict the gel behavior once implanted and submitted to facial dynamics.

The role of hyaluronic acid and amino acid against the aging of the human skin: A clinical and histological study.

In esthetic medicine, different techniques have been used against the aging of the human skin especially in the facial area. Hyaluronic acid is used for improving the quantity of water and extracellular matrix molecule. The aim of this study is a clinical and histological evaluation of the effect of low-molecular-weight hyaluronic acid fragments mixed with amino acid (HAAM) on the rejuvenation the face skin treated with intradermal microinjections. Twenty women with mean age 45 range from 35 to 64 were studied, thereof 8 in menopause and 12 of childbearing age. The patients were treated with the HAAM products by mesotherapy technique; before and after 3months of the therapeutic procedure, each patient underwent small biopsies with a circular punch biopsy. The clinical results of the present study showed that the administration of the dermal filler containing fragments of hyaluronic acid between 20 and 38 monomers and amino acid via dermis injection technique produces an esthetic improvement in the faces of the treated patients, while the histological evaluation shows an increased fibroblast activity with the production of type III reticular collagen and increased number of vessels and epidermis thickness. The clinical and histological assessment showed that subcutaneous HAAM infiltration has a significant impact on the dermis and clinical aspects of the face.