Low Molecular Hyaluronic Acid Research Articles

Hyaluronic Acid Induction Promotes the Differentiation of Human Neural Crest-like Cells into Periodontal Ligament Stem-like Cells.

Periodontal ligament (PDL) stem-like cells (PDLSCs) are promising for regeneration of the periodontium because they demonstrate multipotency, high proliferative capacity, and the potential to regenerate bone, cementum, and PDL tissue. However, the transplantation of autologous PDLSCs is restricted by limited availability. Since PDLSCs are derived from neural crest cells (NCs) and NCs persist in adult PDL tissue, we devised to promote the regeneration of the periodontium by activating NCs to differentiate into PDLSCs. SK-N-SH cells, a neuroblastoma cell line that reportedly has NC-like features, seeded on the extracellular matrix of PDL cells for 2 weeks, resulted in the significant upregulation of PDL marker expression. SK-N-SH cell-derived PDLSCs (SK-PDLSCs) presented phenotypic characteristics comparable to induced pluripotent stem cell (iPSC)-derived PDLSCs (iPDLSCs). The expression levels of various hyaluronic acid (HA)-related genes were upregulated in iPDLSCs and SK-PDLSCs compared with iPSC-derived NCs and SK-N-SH cells, respectively. The knockdown of CD44 in SK-N-SH cells significantly inhibited their ability to differentiate into SK-PDLSCs, while low-molecular HA (LMWHA) induction enhanced SK-PDLSC differentiation. Our findings suggest that SK-N-SH cells could be applied as a new model to induce the differentiation of NCs into PDLSCs and that the LMWHA-CD44 relationship is important for the differentiation of NCs into PDLSCs.

Fabrication of Low-Molecular-Weight Hyaluronic Acid-Carboxymethyl Cellulose Hybrid to Promote Bone Growth in Guided Bone Regeneration Surgery: An Animal Study.

Guided bone regeneration surgery is an important dental operation used to regenerate enough bone to successfully heal dental implants. When this technique is performed on maxilla sinuses, hyaluronic acid (HLA) can be used as an auxiliary material to improve the graft material handling properties. Recent studies have indicated that low-molecular hyaluronic acid (L-HLA) provides a better regeneration ability than high-molecular-weight (H-HLA) analogues. The aim of this study was to fabricate an L-HLA-carboxymethyl cellulose (CMC) hybrid to promote bone regeneration while maintaining viscosity. The proliferation effect of fabricated L-HLA was tested using dental pulp stem cells (DPSCs). The mitogen-activated protein kinase (MAPK) pathway was examined using cells cultured with L-HLA combined with extracellular-signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 inhibitors. The bone growth promotion of fabricated L-HLA/CMC hybrids was tested using an animal model. Micro-computer tomography (Micro-CT) and histological images were evaluated quantitatively to compare the differences in the osteogenesis between the H-HLA and L-HLA. Our results show that the fabricated L-HLA can bind to CD44 on the DPSC cell membranes and affect MAPK pathways, resulting in a prompt proliferation rate increase. Micro CT images show that new bone formation in rabbit calvaria defects treated with L-HLA/CMC was almost two times higher than in defects filled with H-HLA/CMC (p < 0.05) at 4 weeks, a trend that remained at 8 weeks and was confirmed by HE-stained images. According to these findings, it is reasonable to conclude that L-HLA provides better bone healing than H-HLA, and that the L-HLA/CMC fabricated in this study is a potential candidate for improving bone healing efficiency when a guided bone regeneration surgery was performed.

Effects of rooster comb degradation product containing low-molecular hyaluronic acid (INJUV) in individuals with eye dryness; open-label tr.ial with no control group.

Effects of rooster comb degradation product containing low-molecular hyaluronic acid (INJUV) in individuals with eye dryness; open-label tr.ial with no control group.

Efficacy of local injection therapy with hyaluronic acid of different molecular weight in patients with knee osteoarthritis

Intra-articular administration of hyaluronic acid (HA) is one of the methods of conservative treatment of knee osteoarthritis (OA). However, the data of its efficacy in the modern literature are contradictory.Objective: to assess the efficacy of intra-articular administration of HA preparations with different molecular weight in the treatment of patients with knee OA and to study the factors that can influence the effectiveness of such therapy.Subjects and methods. HA preparations were administered to 60 patients with idiopathic and posttraumatic knee OA. The ratio of women to men was 3:1. The average age was 59.5±13.7 years and body mass index – 30.3±5.8 kg/m2. The presence of enthesitis was evaluated prior to treatment by the characteristic clinical picture. The x-ray stage of OA was determined in accordance with the classification of Kellgren–Lawrence. Distribution of of knee joint lesions, relationship of femur and tibia anatomical axes, presence of varus and valgus deformities were also evaluated. The patients were divided into three groups: 18 patients received low-molecular (LM), 19 – medium-molecular (MM) and 23 – high-molecular (HM) HA. To assess the efficacy of the treatment the severity of pain on a visual analog scale (VAS) and the total score of the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire before, 1, 3 and 6 months after treatment were evaluated.Results and discussion. Enthesitis was detected in 17 (28,3%) patients. Stage I of knee OA was diagnosed in 10 (16.6%), II – in 36 (60%) and III – in 14 (23.3%) patients. Varus deformity was detected in 43 (71.7%) patients, neutral axis of the lower limb - in 14 (23.3%), valgus deformity – in 3 (5%). The most significant decrease in the severity of pain was noted in patients with stage I of knee OA: from 54±17.1 to 10.0±10.0 mm. At stage II, the pain decreased from 59.4±12.6 to 45.5±20.3 mm, and at stage III – from 66.4±13.5 to 60.7±23.3 mm. By the 6th month, the severity of pain in patients with enthesitis was higher, and the values of KOOS total score were worse than in patients without it. At stages II and III of knee OA, the ratio of positive to unsatisfactory results for MM, LM and HM HA was as follows: 2:1, 3:1 and 3.6:1. In the group of patients with excellent results, the value of varus deformation averaged 8.5±1.5°, in patients with a good result – 9.8±2.8°, with a satisfactory result – 11.3±4.5°, and with an unsatisfactory – 11.5±3.2°.Conclusion. Intra-articular injection of HA is very effective at stage I of knee OA. The expression and duration of this effect are reducedwith decrease of cartilage thickness and increase of knee joint varus deformation (i.e., at the II and III stages of knee OA). The presence of varus deformation does not affect HA efficacy. Three factors are important: the appearance of varus deformation of the lower limb with initially neutral axis; the increase of varus deformation; the value of varus deformation &gt;10°.

Study for investigation of symptomatic improvement and safety of the ingestion of rooster comb degradation product containing low-molecular hyaluronic acid (INJUV) in individuals with knee and lower back pain; open-label trial with no control group

Study for investigation of symptomatic improvement and safety of the ingestion of rooster comb degradation product containing low-molecular hyaluronic acid (INJUV) in individuals with knee and lower back pain; open-label trial with no control group

Efficacy and Tolerance of an Injectable Medical Device Containing Hyaluronic Acid and Amino acids: A Monocentric Six-Month Open-Label Evaluation

Background: An innovative injectable solution containing low molecular hyaluronic acid (HA) and a specific Amino Acids mixture was formulated to physiologically promote local neo-collagenesis and elastogenesis through fibroblasts chemotaxis migration into the injected area. Objective: Aim of this open clinical trial is to evaluate efficacy and tolerance of the injectable product under study, on main sign of face skin photoaging. Methods: A single Italian center treated 25 female subjects aged 48-65 years with 4 micro-injection sessions with 10-day time laps between each product administration. Subjects were evaluated in basal conditions and after 4, 8, 12 and 24 weeks, using validated clinical scales, subjective evaluations and objective quantitative outcome measures. Assessment of aesthetic results included photographic documentation. Results: Obtained results showed an improvement of all the clinical and subjective assessments and on the majority of objective instrumental parameters. These were already significant 10 days after the first injection procedure and were still significant and still improving after 6 months (at follow up). Global judgment on tolerability was good/excellent, both in the investigators’ opinion and volunteers’ self-evaluation. Conclusions: Obtained results confirm the aesthetic performance of the injectable product on main signs of face skin photoaging. In particular, it was demonstrated the biovolumetric effect, the antiwrinkle efficacy, a superficial and deep moisturising activity and elasticizing properties. This study supports the definition of extracellular matrix targeting (ECM-targeting) for this product.

TOLL-LIKE RECEPTORS IN ISCHEMIA-REPERFUSION INJURY

Ischemia-reperfusion (I/R) injuries are implicated in a large array of pathological conditions such as myocardial infarction, cerebral stroke, and hepatic, renal, and intestinal ischemia, as well as following cardiovascular and transplant surgeries. The hallmark of these pathologies is excessive inflammation. Toll-like receptors (TLRs) are recognized as one of the main contributors to pathogen-induced inflammation and, more recently, injury-induced inflammation. Endogenous ligands such as low-molecular hyaluronic acid, fibronectin, heat shock protein 70, and heparin sulfate were all found to be cleaved in the inflamed tissue and to activate TLR2 and TLR4, initiating an inflammatory response even in the absence of pathogens and infiltrating immune cells. In this review, we discuss the contribution of TLR activation in hepatic, renal, cerebral, intestinal, and myocardial I/R injuries. A greater understanding of the role of TLRs in I/R injuries may aid in the development of specific TLR-targeted therapeutics to treat these conditions.

Esterified hyaluronic acid and autologous bone in the surgical correction of the infra-bone defects.

We study the osteoinductive effect of the hyaluronic acid (HA) by using an esterified low-molecular HA preparation (EHA) as a coadjuvant in the grafting processes to produce bone-like tissue in the presence of employing autologous bone obtained from intra-oral sites, to treat infra-bone defects without covering membrane. We report on 9 patients with periodontal defects treated by EHA and autologous grafting (4 males and 5 females, all non smokers, with a mean age of 43.8 years for females, 40.0 years for males and 42 years for all the group, in good health) with a mean depth of 8.3 mm of the infra-bone defects, as revealed by intra-operative probes. Data were obtained at baseline before treatment and after 10 days, and subsequently at 6, 9, and 24 months after treatment. Clinical results showed a mean gain hi clinical attachment (gCAL) of 2.6mm of the treated sites, confirmed by radiographic evaluation. Such results suggest that autologous bone combined with EHA seems to have good capabilities in accelerating new bone formation in the infra-bone defects.

The effect of oestrogenic treatment on the acid mucopolysaccharide pattern in skin of mice.

Acid mucopolysaccharides obtained from the skin of the back of mice were determined after precipitation with cetylpyridinium chloride and cellulose‐column fractionation. The results are given as μmol uronic acid per gram dry fat free tissue. Following treatment with oestradiol monobenzoate the hyaluronic acid (HA) increased from 2.7 to 14.6, while the chondroitin sulphates were unaffected (3.7 to 4.2). The increase (from 1.3 to 10.8) of a fraction probably consisting of low molecular HA was considered as reflecting an intensified metabolic activity of HA in the connective tissue. A very close linear correlation (r = 0.924) was demonstrated between the increase in the high molecular HA and the increase in tissue water.