Tissue vascularization is a major bottleneck in tissue engineering. In this review, the state of the art on the intricate role of hyaluronic acid (HA) in angiogenesis is explored. HA plays a twofold role in angiogenesis. First, when released as a free polymer in the extracellular matrix (ECM), HA acts as a signaling molecule triggering multiple cascades that foster smooth muscle cell differentiation, migration, and proliferation thereby contributing to vessel wall thickening. Simultaneously, HA bound to the plasma membrane in the pericellular space functions as a polymer block, participating in vessel formation. Starting with the HA origins in native vascular tissues, the approaches aimed at achieving vascularization in vivo are reviewed. The significance of HA molecular weight (MW) in angiogenesis and the challenges associated with utilizing HA in vascular tissue engineering (VTE) are conscientiously addressed. The review finally focuses on a thorough examination and comparison of the diverse strategies adopted to harness the benefits of HA in the vascularization of bioengineered materials. By providing a nuanced perspective on the multifaceted role of HA in angiogenesis, this review contributes to the ongoing discourse in tissue engineering and advances the collective understanding of optimizing vascularization processes assisted by functional biomaterials.

The purpose of this scoping review was to identify possible chondrotoxic effects caused by drugs usually used for intra-articular injections. PubMed, Scopus, Web of Science and Cochrane were searched. Inclusion criteria required randomized controlled trials written in English that evaluate the toxic effect that damages the cartilage. The literature search resulted in 185 unique articles. 133 full-text articles were screened for inclusion, of which 65 were included. Corticosteroids, with the exception of triamcinolone, along with local anaesthetics, potentially excluding ropivacaine and liposomal bupivacaine, and nonsteroidal anti-inflammatory drugs, exhibited insufficient safety profiles to warrant casual use in clinical settings. Hyaluronic acid, on the other hand, appears to demonstrate safety while also mitigating risks associated with concurrent compounds, thereby facilitating therapeutic combinations. Additionally, there remains a paucity of data regarding platelet-rich plasma, necessitating further evaluation of its potential efficacy and safety. Overall, it seems that results are significantly influenced by the dosage and frequency of injections administered, observed in both human and animal studies.

Toward the goal of establishing an engineered model of the vocal fold lamina propria (LP), mesenchymal stem cells (MSCs) are encapsulated in hyaluronic acid (HA)-based hydrogels employing tetrazine ligation with strained alkenes. To mimic matrix stiffening during LP maturation, diffusion-controlled interfacial bioorthogonal crosslinking is carried out on the soft cellular construct using HA modified with a ferocious dienophile, trans-cyclooctene (TCO). Cultures are maintained in MSC growth media for 14 days to afford a model of a newborn LP that is homogeneously soft (nLP), a homogeneously stiffened construct zero (sLP0) or 7 days (sLP7) post cell encapsulation, and a mature LP model (mLP) with a stiff top layer and a soft bottom layer. Installation of additional HA crosslinks restricts cell spreading. Compared to the nLP controls, sLP7 conditions upregulate the expression of fibrous matrix proteins (Col I, DCN, and FN EDA), classic fibroblastic markers (TNC, FAP, and FSP1), and matrix remodeling enzymes (MMP2, TIMP1, and HAS3). Day 7 stiffening also upregulates the catabolic activities, enhances ECM turnover, and promotes YAP expression. Overall, in situ delayed matrix stiffening promotes a fibroblast transition from MSCs and enhances YAP-regulated mechanosensing.

Increased secretion of hyaluronic acid (HA), a glycosaminoglycan abundant in the brain extracellular matrix (ECM), correlates with worse clinical outcomes for glioblastoma (GBM) patients. GBM cells aggressively invade the brain parenchyma while encountering spatiotemporal changes in their local ECM, including HA concentration. To investigate how varying HA concentrations affect GBM invasion, patient-derived GBM cells are cultured within a soft, 3D matrix in which HA concentration is precisely varied and cell migration observed. Data demonstrate that HA concentration can determine the invasive activity of patient-derived GBM cells in a biphasic and highly sensitive manner, where the absolute concentration of HA at which cell migration peaked is specific to each patient-derived line. Furthermore, evidence that this response relies on phosphorylated ezrin, which interacts with the intracellular domain of HA-engaged CD44 to effectively link the actin cytoskeleton to the local ECM is provided. Overall, this study highlights CD44-HA binding as a major mediator of GBM cell migration that acts independently of integrins and focal adhesion complexes and suggests that targeting HA-CD44-ezrin interactions represents a promising therapeutic strategy to prevent tumor cell invasion in the brain.

Hyaluronic acid and amino acids play an important role in the wound healing process, stimulating the development of the connective tissue and the activity and proliferation of fibroblasts. The aim of the present controlled clinical study was to evaluate the clinical efficacy of a topical gel formula containing hyaluronic acid and amino acids in terms of wound closure rate, painkiller intake, and patients\' reported pain and edema.
This study included patients in need of a single tooth extraction. Patients were randomized into two groups with differing post-operative care regimens. Patients in the test group used the amino acid and hyaluronic acid-based gel, while the control group did not use any product. Each parameter was measured in both groups at different time points: immediately after surgery, and after 7, 14, 30, and 60 days.
A total of 40 patients (46.52 ± 9.84 years old) completed the observational period, and 40 extraction sockets were examined. After 7 days, the edema was significantly lower in the test group. The reported pain was lower in the test group without a significant difference, except for the first time point at 7 days. With the follow-up questionnaire, patients declared to have taken painkillers mainly during the first 7 days after surgery; however, the test group showed a lower need for painkillers than the control group.
The post-operative and domiciliary use of an amino acid and hyaluronic acid-based gel for the management of soft tissue closure after tooth extraction is a valid coadjutant to reduce swelling, pain, and the need for painkillers. Additional studies are required to support the results of the present study.

Hyaluronic acid (HA), a multi-functional material, has a high dispersion in molecular weight, and the functions of HA are determined through the size. Nevertheless, hyaluronic acid mixtures are not easily separated due to their polydispersity. In this study, a capillary electrophoresis strategy was developed for resolution of different molecular-weight HA without enzymatic digestion. Here, hyaluronic acid mixtures with low molecular weight (380 kD; LHA) and high molecular weight (2180 kD; HHA) were successfully resolved by the SDS integrated with low molecular-weight polymer in capillary electrophoresis. By optimizing experimental conditions, the separation of LHA and HHA was completed within 14 min. The optimal conditions were as follows: the running buffer was 25 mM borate buffer (pH 9.75) containing 30 mM SDS and 10% polyethylene glycol (MW: 8000); applied voltage was 20 kV (detector at cathode side) and separation temperature was set at 25 °C. The data of method validation showed that calibration plots were linear (r ≥ 0.9977) over a range of 10-50 μg/mL for LHA, and 40-200 μg/mL for HHA. In the evaluation of precision and accuracy for this method, the RSD and RE values were all less than 4.2%. This fascinating technique was successfully applied to the quality control of cosmetic and pharmaceutical containing different ratios of LHA and HHA, and it was feasible for serving as a tool to quantitatively analyze different sizes of HA for clinical survey.

Corticosteroids (CS) or hyaluronic acid (HA) is used in subacromial injection for the conservative treatment of rotator cuff tears (RCT); this study addresses the question of how CS and HA affect the tendon tissue and fibroblasts in vitro and in rats. Cell proliferation assays were performed in human tendon fibroblasts from RCT. Rats underwent surgery to create RCT, and the surgical sites were injected with CS or HA. The rotator cuff tendons were subjected to biomechanical testing, microscopic and immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), and ultrastructural analysis. Cell proliferation was significantly decreased with CS in vitro (p < 0.05). Maximal load of CS-treated tendons was significantly decreased compared with that of HA-treated tendons (p < 0.05), as well as PCNA(+) cells at 2 weeks (p < 0.05). Ultrastructural observations of the CS-treated rats detected apoptosis of tendon fibroblasts 24 h after surgery. Histological and biomechanical data 4 weeks after surgery were not significant among the three groups. Unlike HA, CS caused cell death, and inhibition of the proliferation of tendon fibroblasts, leading to a delay of tendon healing involved and a subsequent decrease of biomechanical strength at the surgical site.

OBJECTIVE: In recent years there has been a growing interest in nonsurgical procedures for facial rejuvenation. Hyaluronic acid is currently the most widely used dermal filler for the treatment of facial wrinkles. However, new products with interesting features are being introduced into the market. Cross-linked carboxymethylcellulose is one of these and represents a new alternative for the correction of wrinkles and facial defects.
METHODS: The retrospective, multicenter, open-label study on nasolabial folds reported here was carried out between January 2010 and April 2014 on 350 subjects between 22 and 67 years of age for a 36-month follow-up period in order to consistently and extensively assess the safety and performance of this treatment.
RESULTS: The study revealed effective and durable correction of nasolabial wrinkles for periods of 9-12 months. Product reapplication over a 36-month period did not lead to an increase in adverse effects, which always remained rare and of little clinical significance, usually consisting of bruising and redness.
CONCLUSIONS: Cross-linked carboxymethyl cellulose has been shown to be a safe and effective alternative to the resorbable products currently on the market.