Consideration of the diameter of superficial temporal arteries related to filler injections in the temporal region.

BACKGROUND: The concavity of the temple due to adipose tissue atrophy from aging accentuates the zygomatic arch and lateral orbital rim, leading to an aged appearance. The use of hyaluronic acid filler in the temporal region has gained popularity due to its procedural simplicity and consistent outcomes. OBJECTIVE: To evaluate the safety of administering hyaluronic acid filler in the temporal region concerning the frontal branch of the superficial temporal artery, which is at risk of injury. METHODS: Empirical observations were conducted on the internal diameter of the frontal branch of the superficial temporal artery, a critical anatomical site for potential injury. RESULTS: A significant proportion of the artery segments exhibited an internal diameter below 1 mm. Given that the outer diameter of an 18-gauge cannula is 1.27 mm, this method can be considered a relatively secure approach for enhancing the temporal region. CONCLUSION: The use of an 18-gauge cannula for hyaluronic acid filler administration in the temporal region appears to be a safe and effective method, with the potential risk to the frontal branch of the superficial temporal artery being minimal.

Intravesical Interferon Therapy vs Hyaluronic Acid for Pain Among Female Individuals With Interstitial Cystitis: A Randomized Clinical Trial.

Importance: Interstitial cystitis (IC) is a debilitating condition. Although viral infection is a potential etiological cause, few studies have detected the effect of antiviral treatment. Objective: To determine the efficacy and safety of intravesical interferon instillation compared with hyaluronic acid in female patients with IC. Design, Setting, and Participants: This double-masked, randomized phase 2/3 clinical trial with parallel group design was implemented from October 2022 to April 2023 and had a 6-month follow-up period. The study was conducted at a single center. Eligible participants were female patients aged 18 to 70 years with a diagnosis of IC for more than 6 months. The last visit took place in October 2023. Data were analyzed between October and November 2023. Intervention: Patients were randomized 1:1 to receive either intravesical instillation of interferon or hyaluronic acid. Main Outcomes and Measures: The primary end point was change in visual analog scale pain score. Secondary end points included changes in voiding frequency, functional bladder capacity, symptom index, and global response assessment. Adverse events were closely monitored. Results: Among the 52 patients, the mean (SD) age was 50.0 (14.1) years and they were randomized to either the interferon group (26 [50%]) or hyaluronic acid (26 [50%]). The visual analog pain score showed the interferon group decreased more significantly than hyaluronic acid (-1.3; 95% CI, -2.3 to -0.3; P = .02) at month 6, with 20 patients (77%) exhibiting a 30% or higher reduction in pain compared with baseline. Secondary end points of voiding frequency, functional bladder capacity, and nocturia episodes showed no significant difference between 2 therapies. However, interferon showed a significantly higher reduction in the Interstitial Cystitis Symptom Index (-3.0; 95% CI, -5.3 to -0.7; P = .01) and the Problem Index (-2.5; 95% CI, -4.5 to -0.4; P = .02) at month 6, with 22 patients (85%) presenting as moderately or markedly improved. The frequencies of adverse events were similar between 2 groups. Only 1 patient discontinued hyaluronic acid because of poor effectiveness. Conclusions and Relevance: In this randomized clinical trial, female patients with IC could benefit from intravesical interferon therapy, without serious adverse events. These results offered hope for antiviral approaches in IC, but larger-scale, multicenter trials and long-term follow-up should be considered. Trial Registration: ClinicalTrials.gov Identifier: NCT05912946.

Dermal injury drives a skin to gut axis that disrupts the intestinal microbiome and intestinal immune homeostasis in mice.

The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.

High molecular weight hyaluronic acid vectorised with clay provides long-term hydration and reduces skin brightness.

BACKGROUND: Hyaluronic acid (HA) is a widely used active cosmetic ingredient. Its multiple skin care benefits are modulated by its molecular weight. Low molecular weight (LMW) HA can penetrate the skin, but high molecular weight (HMW) HA remains at the surface. Here, we assessed how vectorization of HMW HA with bentonite clay-achieved with an innovative technology-enhances its cosmetic and hydrating properties. MATERIALS AND METHODS: The two HA forms were applied to skin explants; their penetration and smoothing effects were monitored by Raman spectroscopy and scanning electron microscopy. The two forms were biochemically characterised by chromatography, enzyme sensitivity assays, and analysis of Zeta potential. Cosmetics benefits such as, the smoothing effect of vectorised-HA was assessed in ex vivo experiments on skin explants. A placebo-controlled clinical study was finally conducted applying treatments for 28 days to analyse the final benefits in crow's feet area. RESULTS: Raman spectroscopy analysis revealed native HMW HA to accumulate at the surface of skin explants, whereas vectorised HMW HA was detected in deeper skin layers. This innovative vectorisation process changed the zeta potential of vectorised HMW HA, being then more anionic and negative without impacting the biochemical structure of native HA. In terms of cosmetic benefits, following application of vectorised HMW HA ex vivo, the skin's surface was visibly smoother. This smoothing was clinically confirmed, with a significant reduction in fine lines. CONCLUSION: The development of innovative process vectorising HMW HA allowed HMW HA penetration in the skin. This enhanced penetration extends the clinical benefits of this iconic cosmetic ingredient.

A pilot study exploring the use of hyaluronic acid in treating insertional achilles tendinopathy.

PURPOSE: This study explores the use of ultrasound-guided Hyaluronic Acid (HA) injections for Insertional Achilles Tendinopathy (IAT). METHODS: A cohort of 15 ankles diagnosed with IAT received three weekly ultrasound-guided HA injections. The Victorian Institute of Sport Assessment - Achilles (VISA-A) questionnaire scored the severity of symptoms and functional impairment before treatment, and at one and six months post-treatment. RESULTS: Significant improvement was observed in VISA-A scores post-treatment, rising from an average baseline of 34.8 ± 15.2 (11-63) to 53.6 ± 20.9 (15-77) after one month, and then to 50.7 ± 18.6 (20-75) after six months. No adverse reactions were noted, underscoring the safety of the intervention. CONCLUSION: The pilot study presents HA injections as a potentially effective treatment for IAT, while interpretation of these findings must take into account the variability in results, indicating a range of patient responses. It encourages further research to confirm these findings and to explore HA's full potential in managing IAT, despite the limitations of a small sample size and lack of control group.

The combination of hyaluronic acid and collagenase in the treatment of skin ulcers: an open, multicenter clinical study assessing safety and tolerability of Bionect Start®.

OBJECTIVE: Several clinical studies have shown that hyaluronic acid collagenase is well-tolerated and very effective in managing chronic venous ulcers. The aim of the present study is to confirm the safety and tolerability of daily application in patients suffering from cutaneous ulcers of different etiologies. The efficacy of the treatment and its impact on patients' quality of life are also assessed. PATIENTS AND METHODS: Patients with a clinical diagnosis of skin ulcer with devitalized/fibrinous/slough tissue that could delay the healing process were enrolled in the study. The hyaluronic acid/collagenase ointment was applied topically until wound closure or total debridement of non-viable tissue was achieved, however, with a limit of 30 days. Monitoring was performed weekly, either through outpatient visits or telephone surveys. Assessments included adverse events, local irritation reactions, pain at dressing changes, and wound bed status. Patients were also requested to complete a quality-of-life questionnaire. RESULTS: The study involved 96 patients with a mean age of 71 years. The patients suffered mainly from traumatic (21.9%), venous (15.6%), or pressure ulcers (12.5%); in 26% of cases, ulcers had mixed etiology. In approximately 32% of patients, the ulcer had been present for more than 6 months, and 18.1% of subjects had previously undergone surgical wound debridement. CONCLUSIONS: Daily application of hyaluronic acid-collagenase achieved the following results: i) absence of adverse events related to the use of the product; ii) significant reduction in the degree of localized irritation and pain at dressing changes; iii) significant support to wound bed preparation; iv) trend towards improvement in the quality of life and health status of the patients.

Patterned PCL/PGS Nanofibrous Hyaluronic Acid-Coated Scaffolds Promote Cellular Response and Modulate Gene Expression Profiles.

Chronic wounds impose a significant burden on individuals and healthcare systems, necessitating the development of advanced wound management strategies. Tissue engineering, with its ability to create scaffolds that mimic native tissue structures and promote cellular responses, offers a promising approach. Electrospinning, a widely used technique, can fabricate nanofibrous scaffolds for tissue regeneration. In this study, we developed patterned nanofibrous scaffolds using a blend of poly(ε-caprolactone) (PCL) and poly(glycerol sebacate) (PGS), known for their biocompatibility and biodegradability. By employing a mesh collector, we achieved a unique fiber orientation pattern that emulated the natural tissue architecture. The average fiber diameter of PGS/PCL collected on aluminum foil and on mesh was found to be 665.2 ± 4 and 404.8 ± 16 nm, respectively. To enhance the scaffolds' bioactivity and surface properties, it was coated with hyaluronic acid (HA), a key component of the extracellular matrix known for its wound-healing properties. The HA coating improved the scaffold hydrophilicity and surface wettability, facilitating cell attachment, spreading, and migration. Furthermore, the HA-coated scaffold exhibited enhanced biocompatibility, promoting cell viability and proliferation. High-throughput RNA sequencing was performed to analyze the influence of the fabricated scaffold on the gene expression levels of endothelial cells. The top-upregulated biological processes and pathways include cell cycle regulation and cell proliferation. The results revealed significant alterations in gene expression profiles, indicating the scaffold's ability to modulate cellular functions and promote wound healing processes. The developed scaffold holds great promise for advanced wound management and tissue regeneration applications. By harnessing the advantages of aligned nanofibers, biocompatible polymers, and HA coating, this scaffold represents a potential solution for improving wound healing outcomes and improving the quality of life for individuals suffering from chronic wounds.

Zinc-Iron Bimetallic Peroxides Modulate the Tumor Stromal Microenvironment and Enhance Cell Immunogenicity for Enhanced Breast Cancer Immunotherapy Therapy.

Immunotherapy has emerged as a potential approach for breast cancer treatment. However, the rigid stromal microenvironment and low immunogenicity of breast tumors strongly reduce sensitivity to immunotherapy. To sensitize patients to breast cancer immunotherapy, hyaluronic acid-modified zinc peroxide-iron nanocomposites (Fe-ZnO2@HA, abbreviated FZOH) were synthesized to remodel the stromal microenvironment and increase tumor immunogenicity. The constructed FZOH spontaneously generated highly oxidative hydroxyl radicals (·OH) that degrade hyaluronic acid (HA) in the tumor extracellular matrix (ECM), thereby reshaping the tumor stromal microenvironment and enhancing blood perfusion, drug penetration, and immune cell infiltration. Furthermore, FZOH not only triggers pyroptosis through the activation of the caspase-1/GSDMD-dependent pathway but also induces ferroptosis through various mechanisms, including increasing the levels of Fe2+ in the intracellular iron pool, downregulating the expression of FPN1 to inhibit iron efflux, and activating the p53 signaling pathway to cause the failure of the SLC7A11-GSH-GPX4 signaling axis. Upon treatment with FZOH, 4T1 cancer cells undergo both ferroptosis and pyroptosis, exhibiting a strong immunogenic response. The remodeling of the tumor stromal microenvironment and the immunogenic response of the cells induced by FZOH collectively compensate for the limitations of cancer immunotherapy and significantly enhance the antitumor immune response to the immune checkpoint inhibitor αPD-1. This study proposes a perspective for enhancing immune therapy for breast cancer.

Effectiveness and Safety of a New Hyaluronic Acid Injectable for Augmentation and Correction of Chin Retrusion.

BACKGROUND: A hyaluronic acid (HA) filler intended for non-surgical improvement of chin appearance should ideally be of high strength/firmness (high G') to allow for deep injections on the bone. HASHA (Restylane Shaype) is a new hyaluronic acid (HA) injectable with high G' and high HA concentration (25 mg/mL), engineered by the new NASHA-HD (High Definition) technology. HASHA is suitable to be placed periosteally, aiming to mimic the natural shape of the bony chin. This pivotal clinical investigation evaluated effectiveness and safety of HASHA for augmentation and correction of chin retrusion.  Methods: Subjects 18 years or older with mild or moderate chin retrusion by the Galderma Chin Retrusion Scale (GCRS), were randomized 3:1 to HASHA (n=103) or no treatment (n=37). Assessments included GCRS (blinded evaluator), aesthetic improvement (Global Aesthetic Improvement Scale [GAIS]), subject satisfaction, and safety.  Results: GCRS responder rate (1-grade or greater improvement from baseline) was significantly higher for HASHA (83.3%) versus controls (10.8%) at month 3 (P<0.001) and maintained through month 12 (P<0.001). Aesthetic improvement was high throughout the study in the HASHA group, according to investigators (97% or greater) and subjects (89% or greater). Overall, subject satisfaction was high at month 3 and maintained at month 12. Product- or injection-related adverse events were mostly mild or moderate and transient. No product- or injection-related serious adverse events were reported. CONCLUSIONS: HASHA, a new NASHA-HD injectable with extra strength/firmness, was safe and effective for chin augmentation and correction of chin retrusion, with high aesthetic improvement and subject satisfaction throughout 12 months. J Drugs Dermatol. 2024;23(4):255-261.     doi:10.36849/JDD.8145.

Evaluation of facial pleasantness in patients with complete and unilateral cleft lip and palate rehabilitated and submitted to orofacial harmonization.

OBJECTIVE: The objective of the present prospective case control study was to evaluate the facial pleasantness of patients with complete and unilateral cleft lip and palate at the end of interdisciplinary rehabilitation, submitted to facial fillers based on hyaluronic acid. METHODS: The study group consisted of 18 individuals with complete unilateral cleft lip and palate, aged between 18 and 40 years (mean age 29 years) of both sexes. The patients presented a concave profile with mild to moderate maxillary deficiency, with completed orthodontic treatment and conducted by means of dentoalveolar compensations without orthognathic surgery. Participants underwent facial filling procedures with hyaluronic acid (HA) in the midface, inserted by a single operator. Standard photographs in frontal norm at rest, right profile at rest, and left profile at rest were obtained from each patient at the following operative times: (T1) pre-filler and (T2) and one-month post-filler. The photographs in T1 and T2 were randomly placed on a page of a virtual album. A 5-point Likert scale was used to assess facial pleasantness. The photographs were evaluated by two groups of evaluators consisting of 18 individuals with cleft lip and palate (CLPG=18) and 18 orthodontists with experience in the treatment of clefts (OG=18). For comparison between phases T1 and T2, and between evaluators with orofacial clefts and orthodontists, the Wilcoxon test was used (p<0,05). RESULTS: People with cleft lip and palate rated their face as more pleasant after the midface filling procedure. In the perception of the orthodontists, on the other hand, the facial pleasantness remained similar after the facial filling procedure. CONCLUSIONS: The filling of the middle third of the face in patients with cleft lip and palate treated without orthognathic surgery increased the pleasantness of the face in the opinion of laypeople with cleft lip and palate.

Hyaluronic acid stimulation of stem cells for cardiac repair: a cell-free strategy for myocardial infarct.

BACKGROUND: Myocardial infarction (MI), a representative form of ischemic heart disease, remains a huge burden worldwide. This study aimed to explore whether extracellular vesicles (EVs) secreted from hyaluronic acid (HA)-primed induced mesenchymal stem cells (HA-iMSC-EVs) could enhance the cardiac repair after MI. RESULTS: HA-iMSC-EVs showed typical characteristics for EVs such as morphology, size, and marker proteins expression. Compared with iMSC-EVs, HA-iMSC-EVs showed enhanced tube formation and survival against oxidative stress in endothelial cells, while reduced reactive oxygen species (ROS) generation in cardiomyocytes. In THP-1 macrophages, both types of EVs markedly reduced the expression of pro-inflammatory signaling players, whereas HA-iMSC-EVs were more potent in augmenting anti-inflammatory markers. A significant decrease of inflammasome proteins was observed in HA-iMSC-EV-treated THP-1. Further, phospho-SMAD2 as well as fibrosis markers in TGF-ß1-stimulated cardiomyocytes were reduced in HA-iMSC-EVs treatment. Proteomic data showed that HA-iMSC-EVs were enriched with multiple pathways including immunity, extracellular matrix organization, angiogenesis, and cell cycle. The localization of HA-iMSC-EVs in myocardium was confirmed after delivery by either intravenous or intramyocardial route, with the latter increased intensity. Echocardiography revealed that intramyocardial HA-iMSC-EVs injections improved cardiac function and reduced adverse cardiac remodeling and necrotic size in MI heart. Histologically, MI hearts receiving HA-iMSC-EVs had increased capillary density and viable myocardium, while showed reduced fibrosis. CONCLUSIONS: Our results suggest that HA-iMSC-EVs improve cardiac function by augmenting vessel growth, while reducing ROS generation, inflammation, and fibrosis in MI heart.

Multifunctional fucoidan-loaded Zn-MOF-encapsulated microneedles for MRSA-infected wound healing.

Infected wound healing remains a challenging task in clinical practice due to several factors: (I) drug-resistant infections caused by various pathogens, (II) persistent inflammation that hinders tissue regeneration and (III) the ability of pathogens to persist intracellularly and evade antibiotic treatment. Microneedle patches (MNs), recognized for their effecacious and painless subcutaneous drug delivery, could greatly enhance wound healing if integrated with antibacterial functionality and tissue regenerative potential. A multifunctional agent with subcellular targeting capability and contained novel antibacterial components, upon loading onto MNs, could yield excellent therapeutic effects on wound infections. In this study, we sythesised a zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) loaded with low molecular weight fucoidan (Fu) and further coating by hyaluronic acid (HA), obtained a multifunctional HAZ@Fu NPs, which could hinders Methicillin-resistant Staphylococcus aureus (MRSA) growth and promotes M2 polarization in macrophages. We mixed HAZ@Fu NPs with photocrosslinked gelatin methacryloyl (GelMA) and loaded it into the tips of the MNs (HAZ@Fu MNs), administered to mice model with MRSA-infected full-thickness cutaneous wounds. MNs are able to penetrate the skin barrier, delivering HAZ@Fu NPs into the dermal layer. Since cells within infected tissues extensively express the HA receptor CD44, we also confirmed the HA endows the nanoparticles with the ability to target MRSA in subcellular level. In vitro and in vivo murine studies have demonstrated that MNs are capable of delivering HAZ@Fu NPs deep into the dermal layers. And facilitated by the HA coating, HAZ@Fu NPs could target MRSA surviving at the subcellular level. The effective components, such as zinc ions, Fu, and hyaluronic acid could sustainably released, which contributes to antibacterial activity, mitigates inflammation, promotes epithelial regeneration and fosters neovascularization. Through the RNA sequencing of macrophages post co-culture with HAZ@Fu, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis reveals that the biological functionalities associated with wound healing could potentially be facilitated through the PI3K-Akt pathway. The results indicate that the synergistic application of HAZ@Fu NPs with biodegradable MNs may serve as a significant adjunct in the treatment of infected wounds. The intricate mechanisms driving its biological effects merit further investigation.

Redox-Responsive Gold Nanoparticles Coated with Hyaluronic Acid and Folic Acid for Application in Targeting Anticancer Therapy.

Methotrexate (MTX) has poor water solubility and low bioavailability, and cancer cells can become resistant to it, which limits its safe delivery to tumor sites and reduces its clinical efficacy. Herein, we developed novel redox-responsive hybrid nanoparticles (NPs) from hyaluronic acid (HA) and 3-mercaptopropionic acid (MPA)-coated gold NPs (gold@MPA NPs), which were further conjugated with folic acid (FA). The design of FA-HA-ss-gold NPs aimed at enhancing cellular uptake specifically in cancer cells using an active FA/HA dual targeting strategy for enhanced tumor eradication. MTX was successfully encapsulated into FA-HA-ss-gold NPs, with drug encapsulation efficiency (EE) as high as >98.7%. The physicochemical properties of the NPs were investigated in terms of size, surface charges, wavelength reflectance, and chemical bonds. MTX was released in a sustained manner in glutathione (GSH). The cellular uptake experiments showed effective uptake of FA-HA-ss-gold over HA-ss-gold NPs in the deep tumor. Moreover, the release studies provided strong evidence that FA-HA-ss-gold NPs serve as GSH-responsive carriers. In vitro, anti-tumor activity tests showed that FA-HA-ss-gold/MTX NPs exhibited significantly higher cytotoxic activity against both human cervical cancer (HeLa) cells and breast cancer (BT-20) cells compared to gold only and HA-ss-gold/MTX NPs while being safe for human embryonic kidney (HEK-293) cells. Therefore, this present study suggests that FA-HA-ss-gold NPs are promising active targeting hybrid nanocarriers that are stable, controllable, biocompatible, biodegradable, and with enhanced cancer cell targetability for the safe delivery of hydrophobic anticancer drugs.

A paclitaxel-hyaluronan conjugate (ONCOFID-P-B™) in patients with BCG-unresponsive carcinoma in situ of the bladder: a dynamic assessment of the tumor microenvironment.

BACKGROUND: The intravesical instillation of the paclitaxel-hyaluronan conjugate ONCOFID-P-B™ in patients with bacillus Calmette-Guérin (BCG)-unresponsive bladder carcinoma in situ (CIS; NCT04798703 phase I study), induced 75 and 40% of complete response (CR) after 12 weeks of intensive phase and 12 months of maintenance phase, respectively. The aim of this study was to provide a detailed description of the tumor microenvironment (TME) of ONCOFID-P-B™-treated BCG-unresponsive bladder CIS patients enrolled in the NCT04798703 phase I study, in order to identify predictive biomarkers of response. METHODS: The composition and spatial interactions of tumor-infiltrating immune cells and the expression of the most relevant hyaluronic acid (HA) receptors on cancer cells, were analyzed in biopsies from the 20 patients enrolled in the NCT04798703 phase I study collected before starting ONCOFID-P-B™ therapy (baseline), and after the intensive and the maintenance phases. Clinical data were correlated with cell densities, cell distribution and cell interactions. Associations between immune populations or HA receptors expression and outcome were analyzed using univariate Cox regression and log-rank analysis. RESULTS: In baseline biopsies, patients achieving CR after the intensive phase had a lower density of intra-tumoral CD8+ cytotoxic T lymphocytes (CTL), but also fewer interactions between CTL and macrophages or T-regulatory cells, as compared to non-responders (NR). NR expressed higher levels of the HA receptors CD44v6, ICAM-1 and RHAMM. The intra-tumoral macrophage density was positively correlated with the expression of the pro-metastatic and aggressive variant CD44v6, and the combined score of intra-tumoral macrophage density and CD44v6 expression had an AUC of 0.85 (95% CI 0.68-1.00) for patient response prediction. CONCLUSIONS: The clinical response to ONCOFID-P-B™ in bladder CIS likely relies on several components of the TME, and the combined evaluation of intra-tumoral macrophages density and CD44v6 expression is a potentially new predictive biomarker for patient response. Overall, our data allow to advance a potential rationale for combinatorial treatments targeting the immune infiltrate such as immune checkpoint inhibitors, to make bladder CIS more responsive to ONCOFID-P-B™ treatment.

Tetrahedral framework nucleic acids/hyaluronic acid-methacrylic anhydride hybrid hydrogel with antimicrobial and anti-inflammatory properties for infected wound healing.

Bacterial resistance and excessive inflammation are common issues that hinder wound healing. Antimicrobial peptides (AMPs) offer a promising and versatile antibacterial option compared to traditional antibiotics, with additional anti-inflammatory properties. However, the applications of AMPs are limited by their antimicrobial effects and stability against bacterial degradation. TFNAs are regarded as a promising drug delivery platform that could enhance the antibacterial properties and stability of nanodrugs. Therefore, in this study, a composite hydrogel (HAMA/t-GL13K) was prepared via the photocross-linking method, in which tFNAs carry GL13K. The hydrogel was injectable, biocompatible, and could be instantly photocured. It exhibited broad-spectrum antibacterial and anti-inflammatory properties by inhibiting the expression of inflammatory factors and scavenging ROS. Thereby, the hydrogel inhibited bacterial infection, shortened the wound healing time of skin defects in infected skin full-thickness defect wound models and reduced scarring. The constructed HAMA/tFNA-AMPs hydrogels exhibit the potential for clinical use in treating microbial infections and promoting wound healing.

The application of phenylboronic acid pinacol ester functionalized ROS-responsive multifunctional nanoparticles in the treatment of Periodontitis.

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.

[Preliminarily study of arthrocentesis combined with liquid phase concentrated growth factor injection in the treatment of unilateral temporomandibular joint osteoarthritis].

OBJECTIVE: To observe the clinical effect of arthrocentesis combined with liquid phase concentrated growth factor (CGF) injection in the treatment of unilateral temporomandibular joint osteoarthritis (TMJOA), in order to provide a new treatment option for TMJOA patients. METHODS: In this non-randomized controlled study, patients diagnosed with unilateral TMJOA who visited the center for temporomandibular joint disorder and orofacial pain of Peking University School and Hospital of Stomatology from June 2021 to January 2023 were selected as research objects. The patients were divided into experimental group and control group, which were selected by patients themselves. The experimental group received arthrocentesis combined with liquid phase CGF injection and the control group received arthrocentesis combined with HA injection. Both groups were treated 3 times, once every two weeks. The clinical effect was evaluated by the maximum mouth opening, pain value and the degree of mandibular function limitation 6 months after treatment. The change of condylar bone was evaluated by cone beam CT (CBCT) image fusion technology before and after treatment. RESULTS: A total of 20 patients were included in the experimental group, including 3 males and 17 females, with an average age of (34.40±8.41) years. A total of 15 patients were included in the control group, including 1 male and 14 females, with an average age of (32.20±12.00) years. There was no statistical difference in general information between the two groups (P > 0.05). There were no statistical differences in the mouth opening, pain value and the degree of jaw function limitation between the two groups before treatment (P > 0.05), and all of them improved 6 months after treatment compared with before treatment (P < 0.05). However, the mouth opening of experimental group was significantly higher than that of control group 6 months after treatment (P < 0.05), and the degree of jaw function limitation was significantly lower than that of control group (P < 0.05). CBCT 2D images showed that the condylar bone of both groups was smoother after treatment than before treatment, and image fusion results showed that 10 patients (50.0%) in the experimental group and 5 patients (33.3%) in the control group had reparative remodeling area of condylar bone, and there was no statistical difference between them (P > 0.05). Except for one CGF patient, the other patients in both groups had some absorption areas of condylar bone. CONCLUSION: The arthrocentesis combined with liquid phase CGF injection can improve the clinical symptoms and signs of unilateral TMJOA patients in short term, and is better than HA in increasing mouth opening and improving jaw function. CBCT fusion images of both patient groups show some cases of condylar bone reparative remodeling and its relevance to treatment plans still requires further study.

Bile Acid-Targeted Hyaluronic Acid Nanoparticles for Enhanced Oral Absorption of Deferoxamine.

Patients with ß-thalassemia and sickle cell disease often rely on blood transfusions which can lead to hemochromatosis and chronic oxidative stress in cells and tissues. Deferoxamine (DFO) is clinically approved to treat hemochromatosis but is suboptimal to patients due to its poor pharmacokinetics which requires long-term infusion regimens. Although the oral route is preferable, DFO has limited oral bioavailability. Studies have shown that hyaluronic acid (HA) and bile acid (BA) can enhance the oral absorption of poorly absorbed drugs. To improve upon the oral delivery of DFO, we report on the synthesis and characterization of HA (MW 15 kD) conjugated to two types of BA, deoxycholic acid (DOCA) and taurocholic acid (TCA), and DFO. The resulting seven polymeric conjugates all formed self-assembled nanoparticles. The degree of BA and DFO conjugation to the HA polymer was confirmed at each step through nuclear magnetic resonance, Fourier transform infrared spectroscopy, and UV-Vis spectroscopy. The best formulations for further in vitro testing were determined based on physicochemical characterizations and included HA-DFO, TCA9-HA-DFO, and DOCA9-HA-DFO. Results from in vitro assays revealed that TCA9-HA-DFO enhanced the permeation of DFO the most and was also less cytotoxic to cells compared to the free drug DFO. In addition, ferritin reduction studies indicated that the conjugation of DFO to TCA9-HA did not compromise its chelation efficiency at equivalent free DFO concentrations. This research provides supportive data for the idea that TCA conjugated to HA may enhance the oral absorption of DFO, improve its cytocompatibility, and maintain its iron chelation efficiency.

Nanotechnological Research for Regenerative Medicine: The Role of Hyaluronic Acid.

Hyaluronic acid (HA) is a linear, anionic, non-sulfated glycosaminoglycan occurring in almost all body tissues and fluids of vertebrates including humans. It is a main component of the extracellular matrix and, thanks to its high water-holding capacity, plays a major role in tissue hydration and osmotic pressure maintenance, but it is also involved in cell proliferation, differentiation and migration, inflammation, immunomodulation, and angiogenesis. Based on multiple physiological effects on tissue repair and reconstruction processes, HA has found extensive application in regenerative medicine. In recent years, nanotechnological research has been applied to HA in order to improve its regenerative potential, developing nanomedical formulations containing HA as the main component of multifunctional hydrogels systems, or as core component or coating/functionalizing element of nanoconstructs. This review offers an overview of the various uses of HA in regenerative medicine aimed at designing innovative nanostructured devices to be applied in various fields such as orthopedics, dermatology, and neurology.