Supraperiosteal technique protocol for forehead filling with a mixture of calcium hydroxyapatite and hyaluronic acid: Double-blind, randomized controlled clinical trial.

OBJECTIVE: The current study aims to investigate the safety and efficacy of using calcium hydroxyapatite (CaHA) versus CaHA associated with hyaluronic acid (HA) for forehead volume replacement and contour restoration without forehead irregularities. METHODS: This interventional study involved 132 participants in a two-arm, parallel, double-blind trial for forehead treatment using the supraperiosteal technique. Group A received CaHA, and Group B received a combination of CaHA and HA as filler materials. Follow-up assessments occurred at 30 and 180 days, incorporating the 5-point Global Aesthetic Improvement Scale (GAIS) and photographic analysis for forehead volume replacement, contour restoration, and without forehead irregularities. Safety assessments included monitoring adverse events, particularly nodules. RESULTS: The study included all 132 enrolled patients who completed the trial. Applying CaHA in combination with HA resulted in a statistically significant improvement in both GAIS scale scores and the reduction of forehead irregularities. The total incidence of nodules was 3.7%. Group A had four times more occurrences of nodules than Group B. Furthermore, Group B exhibited lower rates of forehead irregularities following the treatment compared to Group A. CONCLUSION: The supraperiosteal application of CaHA and HA for forehead treatment demonstrates superior efficacy in addressing signs of aging compared to the isolated use of CaHA.

Tumor-targeted delivery of hyaluronic acid/polydopamine-coated Fe2+-doped nano-scaled metal-organic frameworks with doxorubicin payload for glutathione depletion-amplified chemodynamic-chemo cancer therapy.

Chemodynamic therapy (CDT), an emerging cancer treatment modality, uses multivalent metal elements to convert endogenous hydrogen peroxide (H2O2) to toxic hydroxyl radicals (•OH) via a Fenton or Fenton-like reaction, thus eliciting oxidative damage of cancer cells. However, the antitumor potency of CDT is largely limited by the high glutathione (GSH) concentration and low catalytic efficiency in the tumor sites. The combination of CDT with chemotherapy provides a promising strategy to overcome these limitations. In this work, to enhance antitumor potency by tumor-targeted and GSH depletion-amplified chemodynamic-chemo therapy, the hyaluronic acid (HA)/polydopamine (PDA)-decorated Fe2+-doped ZIF-8 nano-scaled metal-organic frameworks (FZ NMs) were fabricated and utilized to load doxorubicin (DOX), a chemotherapy drug, via hydrophobic, π-π stacking and charge interactions. The attained HA/PDA-covered DOX-carrying FZ NMs (HPDFZ NMs) promoted DOX and Fe2+ release in weakly acidic and GSH-rich milieu and exhibited acidity-activated •OH generation. Through efficient CD44-mediated endocytosis, the HPDFZ NMs internalized by CT26 cells not only prominently enhanced •OH accumulation by consuming GSH via PDA-mediated Michael addition combined with Fe2+/Fe3+ redox couple to cause mitochondria damage and lipid peroxidation, but also achieved intracellular DOX release, thus eliciting apoptosis and ferroptosis. Importantly, the HPDFZ NMs potently inhibited CT26 tumor growth in vivo at a low DOX dose and had good biosafety, thereby showing promising potential in tumor-specific treatment.

Hydrogels with Antioxidant Microparticles Systems Based on Hyaluronic Acid for Regenerative Wound Healing.

This research focuses on the synthesis of hydrogels exhibiting enhanced antioxidant properties derived from hyaluronic acid (HA) and poly(ethylene brassylate-co-squaric acid) (PEBSA), a copolymacrolactone that have the ability to be used in drug delivery applications. Quercetin (Q), a bioflavonoid with strong antioxidant properties, is employed as a bioactive compound. The biomolecule is encapsulated in the polymeric network using different entrapment techniques, including the initial formation of a complex between PEBSA and Q, which is demonstrated through the dynamic light scattering technique. Fourier transform infrared spectroscopy (FT-IR) and rheological studies confirm the formation of the hydrogels, revealing the occurrence of physical interactions between the synthetic polymer and the polysaccharide. Moreover, the hydrogels demonstrate biocompatible properties after direct contact with the HDFa cell line and antioxidant properties, as revealed by DPPH tests.

Are We Overlooking Harms of BDDE-Cross-Linked Dermal Fillers? A Scoping Review.

1,4-Butanediol ether (BDDE) is widely used as a cross-linker for hyaluronic acid in dermal fillers. The purpose of this scoping review was to determine the state of knowledge about the behaviour of cross-linked substances and safety of BDDE application. The rationale behind the review came from the clinical experience of the corresponding author, who noticed adverse reactions after BDDE-linked hyaluronan application. The scoping review was conducted according to PRISMA-ScR guidelines. Out of 399 articles, 52 met the inclusion criteria. Data on study design, sample/population, aims, methodology, outcomes and funding were extracted. Results were charted according to 6 subtopics: rheological properties, hydrogel stability, BDDE toxicity, immunogenicity, tissue interactions and clinical studies. In vitro, cross-linked hydrogels were characterized as effective fillers in terms of viscosity and elasticity; however, previously uncharacterized by-products of the cross-linking reaction were found. Most in vivo studies reported increased dermis regeneration, vascularization and anti-inflammatory cytokine release after implantation of BDDE-cross-linked substances. In clinical studies, BDDE was shown to sensitize subjects to 1,6-hexanediol ether and other substances found in epoxy resin systems. Occupational dermatitis and hypersensitivity reactions were documented. Our review shows that BDDE may have long-term adverse effects, which are overlooked in the safety assessment of fillers. Reviews on BDDE conducted so far have mostly been sponsored by the industry, potentially leading to incomplete reporting of adverse effects. A review of the occurrence of allergic reactions after commercial dermal filler use and analysis of possibly harmful by-products of BDDE hyaluronan degradation are needed.Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Antibacterial properties of photo-crosslinked chitosan/methacrylated hyaluronic acid nanoparticles loaded with bacitracin.

The current treatments for wounds often fail to produce adequate healing, leaving wounds vulnerable to persistent infections and development of drug-resistant microbial biofilms. New natural-derived nanoparticles were studied to impair bacteria colonization and hinder the formation of biofilms in wounds. The nanoparticles were fabricated through polyelectrolyte complexation of chitosan (CS, polycation) and hyaluronic acid (HA, polyanion). UV-induced photo-crosslinking was used to enhance the stability of the nanoparticles. To achieve this, HA was methacrylated (HAMA, degree of modification of 20 %). Photo-crosslinked nanoparticles obtained from HAMA and CS had a diameter of 478 nm and a more homogeneous size distribution than nanoparticles assembled solely through complexation (742 nm). The nanoparticles were loaded with the antimicrobial agent bacitracin (BC), resulting in nanoparticles with a diameter of 332 nm. The encapsulation of BC was highly efficient (97 %). The BC-loaded nanoparticles showed significant antibacterial activity against gram-positive bacteria Staphylococcus aureus, Methicillin-resistant S. aureus and S. epidermidis. The nanoparticles loaded with BC based on photo-crosslinked HAMA/CS demonstrated inhibition of biofilm formation and a positive effect on the proliferation of mammalian cells (L929). These crosslinked nanoparticles have potential for the long-term treatment of wounds and controlled antibiotic delivery at the location of a lesion.

Comment to: Static and Dynamic Filler-Associated Tear Trough Deformities: Manifestations and Treatment Algorithm.

Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Carnosine and Retinol Synergistically Inhibit UVB-Induced PGE2 Synthesis in Human Keratinocytes through the Up-Regulation of Hyaluronan Synthase 2.

Skin aging results from complex interactions of intrinsic and extrinsic factors, leading to structural and biochemical changes such as wrinkles and dryness. Ultraviolet (UV) irradiation leads to the degradation of hyaluronic acid (HA) in the skin, and the with fragmented HA contributes to inflammation. This study revealed that the synergistic combination of carnosine and retinol (ROL) increases HA production in normal human epidermal keratinocytes (NHEKs) by upregulating hyaluronan synthase 2 (HAS2) gene transcription. Simultaneously, the combined treatment of carnosine and ROL significantly attenuates UVB-induced prostaglandin E2 (PGE2) synthesis in NHEKs. A significant correlation exists between the increase of HA synthesis and the inhibition of PGE2 production. This study suggested that combined treatment of carnosine and ROL can improve skin aging phenotypes associated with UVB irradiation.

Rational development of functional hydrophilic polymer to characterize site-specific glycan differences between bovine milk and colostrum.

As vastly modified on secreted proteins, N-glycosylation is found on milk proteins and undergo dynamic changes during lactation, characterizing milk protein glycosylation would benefit the elucidation of glycosylation pattern differences between samples. However, their low abundance required specific enrichment. Herein, through rational design and controllable synthesis, we developed a novel multi-functional polymer for the isolation of protein glycosylation. It efficiently separated glycopeptides from complex background inferences with mutual efforts of hydrophilic interaction chromatography (HILIC), metal ion affinity and ion exchange. By fine-tuning Ca2+ as regulators of aldehyde hyaluronic acid (HA) conformation, the grafting density of HA was remarkably improved. Moreover, grafting Ti4+ further enhanced the enrichment performance. Application of this material to characterize bovine milk and colostrum proteins yields 479 and 611 intact glycopeptides, respectively. Comparative analysis unraveled the distinct glycosylation pattern as well the different distribution of glycoprotein abundances between the two samples, offering insights for functional food development.

Efficacy of a single ultrasound-guided injection of high molecular weight hyaluronic acid combined with collagen tripeptide in patients with knee osteoarthritis and chondrocalcinosis.

Introduction: Osteoarthritis (OA) and calcium pyrophosphate deposition (CPPD) often co-exist, this resulting in a clinical condition characterized by amplified inflammation and more severe and faster cartilage degeneration compared to OA alone. Our study aims to explore the efficacy of a therapeutic approach that addresses both conditions, using a combination of a high molecular weight hyaluronic acid (HMWHA) and collagen tripeptide (CTP). Additionally, safety profile and baseline characteristic predictive value were evaluated. Methods: We conducted a retrospective study on patients diagnosed with symptomatic knee OA (KOA) and CPPD treated by ultrasound (US) guided intraarticular injections of HMWHA-CT in the outpatient clinics of the Interdisciplinary Pain Medicine Unit at Santa Maria Maddalena Hospital, Occhiobello, Italy and in the Rheumatology Unit of the Emergency County Hospital Craiova, Romania (ECH Craiova). All the patients underwent clinical and US evaluation at baseline, 1, 3, and 6 months. From clinical point of view, Numeric Rating Scale (NRS) pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were recorded. US data included detection of synovitis, cartilage damage, osteophytes, and CPPD deposits. Clinical efficacy was defined with NRS and WOMAC variations in respect to baseline and using the minimal clinically important difference values: an improvement of 2 point for NRS pain and 10 for the total score for WOMAC. Results: Twenty-nine patients (34 knees) were injected and evaluated. Overall pain levels, as measured by NRS, demonstrated a consistent decrease in patients across all follow-up intervals, with the most substantial improvement at the 6-month compared to baseline measurements. A significative proportion of patients achieved the minimum clinically detectable improvement, specifically 79% for NRS and 83% for WOMAC (19 and 20 patients, respectively). Conclusion: Our data showed a significant efficacy of ultrasound guided HMWHA-CT, in patients with KOA and CPPD, thus making it reasonable to consider that the combination of HMWHA and CTP can provide a strong anti-inflammatory effect.

Delivery of siRNAs Against Selective Ion Channels and Transporter Genes Using Hyaluronic Acid-coupled Carbonate Apatite Nanoparticles Synergistically Inhibits Growth and Survival of Breast Cancer Cells.

Introduction: Dysregulated calcium homeostasis and consequentially aberrant Ca2+ signalling could enhance survival, proliferation and metastasis in various cancers. Despite rapid development in exploring the ion channel functions in relation to cancer, most of the mechanisms accounting for the impact of ion channel modulators have yet to be fully clarified. Although harnessing small interfering RNA (siRNA) to specifically silence gene expression has the potential to be a pivotal approach, its success in therapeutic intervention is dependent on an efficient delivery system. Nanoparticles have the capacity to strongly bind siRNAs. They remain in the circulation and eventually deliver the siRNA payload to the target organ. Afterward, they interact with the cell surface and enter the cell via endocytosis. Finally, they help escape the endo-lysosomal degradation system prior to unload the siRNAs into cytosol. Carbonate apatite (CA) nanocrystals primarily is composed of Ca2+, carbonate and phosphate. CA possesses both anion and cation binding domains to target negatively charged siRNA molecules. Methods: Hybrid CA was synthesized by complexing CA NPs with a hydrophilic polysaccharide - hyaluronic acid (HA). The average diameter of the composite particles was determined using Zetasizer and FE-SEM and their zeta potential values were also measured. Results and Discussion: The stronger binding affinity and cellular uptake of a fluorescent siRNA were observed for HA-CA NPs as compared to plain CA NPs. Hybrid CA was electrostatically bound individually and combined with three different siRNAs to silence expression of calcium ion channel and transporter genes, TRPC6, TRPM8 and SLC41A1 in a human breast cancer cell line (MCF-7) and evaluate their potential for treating breast cancer. Hybrid NPs carrying TRPC6, TRPM8 and SLC41A1 siRNAs could significantly enhance cytotoxicity both in vitro and in vivo. The resultant composite CA influenced biodistribution of the delivered siRNA, facilitating reduced off target distribution and enhanced breast tumor targetability.

Limited Evidence to Support the Use of Intra-Articular Injection of Hyaluronic Acid for the Management of Hallux Rigidus: A Systematic Review.

Background: The purpose of this systematic review was to evaluate outcomes following intra-articular injection of hyaluronic acid (HA) for the treatment of hallux rigidus. Methods: During April 2024, a systematic review of the MEDLINE, EMBASE, and Cochrane Library databases was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data collected and analyzed were number of patients, patient age, follow-up, subjective clinical outcomes, complications, and failures. Results: Five studies were included. In total, 218 patients (218 feet) underwent intra-articular injection of HA at a weighted mean follow-up time of 4.4 ± 1.4 months (range, 3-6). There was an improvement in postinjection visual analog scale (VAS) pain at rest scores, VAS pain during activity scores, American Orthopaedic Foot & Ankle Society (AOFAS) scores, and Foot Health Status Questionnaire (FHSQ) scores. In total, 21 complications (10.0%) were observed, the most common of which was transient postinjection pain in 20 patients (9.6%). There were 7 patients (3.2%) who underwent secondary procedures (3.2%). One randomized control trial (RCT) demonstrated no difference in outcomes between an intra-articular injection of HA compared to an intra-articular injection of saline. One RCT demonstrated superior FHSQ scores following between an intra-articular injection of HA compared to an intra-articular injection of triamcinolone acetonide. Conclusion: This systematic review suggests that intra-articular injection of HA for the treatment of hallux rigidus may lead to improved clinical outcomes with a low complication rate at short-term follow-up. However, the low level and quality of evidence underscores the need for further high-quality studies to be conducted to identify the precise role of HA in the treatment of hallux rigidus.

Termo de consentimento livre e esclarecido e sua relação com os procedimentos de preenchimento labial / Free and informed consent terms and its relationship with lip filling procedures

Introdução: Na medida em que envelhecemos os lábios estreitam-se, ocasionando perda de volume e contorno e como forma de minimizar este efeito fisiológico o preenchimento labial de escolha utilizado é o ácido hialurônico. É possível perceber efeitos adversos advindos do emprego deste material, e pelo fato da informação ao paciente ser assegurada pelo Código de Defesa do Consumidor e pelo fato da necessidade dos Cirurgiões-Dentistas terem de esclarecer seus pacientes, o Termo de Consentimento Livre e Esclarecido tornase necessário. Objetivo: identificar, por meio de aplicação de questionário, a percepção de profissionais que trabalham com Harmonização Orofacial em relação a necessidade do emprego do Termo de Consentimento Livre e Esclarecido (TCLE). O questionário apresentou 6 perguntas objetivas, que foram disponibilizadas na plataforma Google Forms®. Material e Método: os dados obtidos foram tabulados em uma planilha eletrônica do programa Microsoft Excel e após analisados descritivamente através de tabelas de frequência, porcentagens e gráficos estatísticos. Resultados: dentre os entrevistados foi constatado que a maioria, 87,5% dos especialistas em Harmonização Orofacial realizam o procedimento de preenchimento labial em sua rotina clínica, e 12,5% não. Conclusão: no presente estudo identificamos que os especialistas realizam o emprego do TCLE, em sua maioria, porém, alguns destes ainda negligenciam o seu uso(AU)

Introduction: As we age, the lips become thinner and to minimize this effect, the lip filler used is hyaluronic acid. It is possible to notice adverse effects arising from the use of this material, and it is extremely important that Dental Surgeons have to clarify their patients, the Free and Informed Consent Form becomes necessary. Objective: to identify, through the application of a questionnaire, the perception of professionals who work with Orofacial Harmonization in relation to the need to use the Free and Informed Consent Form (TCLE). The questionnaire presented 6 objective questions, which were made available on the Google Forms® platform. Materials and Methods: the data obtained were tabulated in a Microsoft Excel spreadsheet and then analyzed descriptively using frequency tables, percentages and graphs. Results: among those interviewed, it was found that the majority, 87.5% of specialists in Orofacial Harmonization perform the lip filling procedure in their clinical routine, and 12.5% do not. With the high percentage of 59.4%, it was possible to verify that the majority of professionals perform 1 to 3 procedures per month; 31.3% perform 4 to 9 procedures per month; and 9.4% of 10 or more monthly procedures. Conclusion: in the present study it was possible to identify that the majority of specialists in Orofacial Harmonization use the informed consent form, however, some of them still neglect its use(AU)

Transcutaneous Laryngeal Ultrasound for Assessing Hyaluronic Acid Status in Patients Undergoing Injection Laryngoplasty.

OBJECTIVE: Injection laryngoplasty (IL) with hyaluronic acid (HA) is an effective treatment for patients with glottic insufficiency. The duration of HA maintenance in the vocal fold remains unknown. In this study, transcutaneous laryngeal ultrasound (TLUS) was used to evaluate the absorption and migration of HA after IL. Subsequent management might be provided based on the TLUS finding. METHODS: Patients diagnosed with unilateral vocal fold paralysis (UVFP) or vocal fold atrophy were recruited. All patients underwent IL with HA in an office-based setting along with TLUS to monitor the status of HA. The schedule of TLUS included assessments before and after IL until non-visualization. RESULTS: The study population comprised 38 women and 17 men. Of the patients, 54.1% underwent IL for UVFP, whereas 45.9% underwent IL for vocal fold atrophy. Multivariate Cox regression analysis for factors affecting HA absorption revealed that the cause of injection was the most important independent predictor (hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.03-4.46; p = 0.040). The duration of HA maintenance was significantly longer in patients with UVFP than in those with vocal fold atrophy (8.77 vs. 4.70 months, HR, 2.33; 95% CI, 5.47-8.18; p = 0.002). CONCLUSION: TLUS is an objective assessment method for patients undergoing IL with HA. Subsequent tailor-made management could be offered based on the TLUS findings during follow-up. For patients at high risk of upper respiratory tract infection or who are intolerant to flexible nasopharyngoscopy, TLUS can be used as an alternative tool to evaluate the condition of the glottis after IL with HA. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

Infiltrative Treatment of Morton's Neuroma: A Systematic Review.

BACKGROUND: Morton's neuroma (MN) is one of the most frequent neurological pathologies in feet, affecting approximately 4% of the general population. The treatment of MN can be surgical, conservative, and infiltrative, with different substances used in the injections for MN, as steroids, sclerosing solutions, and others. This review aims to evaluate the efficacy of current infiltrative therapy for Morton's neuroma and, additionally, to define adverse effects of this therapy. MATERIAL AND METHODS: A literature search was performed in PubMed, Embase, CINHAL, Epistemonikos, Web of Science (WOS), SPORTSDiscus and Cochrane Library. This search involved the application of all types of infiltrative treatment applicable to MN. The search was limited to original data describing clinical outcomes and pain using the Visual Analogue pain Scale (VAS) or the Johnson Satisfaction Scale, between February and June 2023. RESULTS: Twelve manuscripts were selected (six randomized controlled trials and six longitudinal observational studies) involving 1,438 patients. Capsaicin was reported to produce a VAS score reduction of 51.8%. Corticosteroids also reported a high level of efficacy. Alcohol and Hyaluronic Acid injections are well tolerated, but the effects of their application need further research. There were no serious adverse events. CONCLUSIONS: Corticosteroids, sclerosant injections, hyaluronic acid and capsaicin have been shown to be effective in reducing the pain related to MN.

Delayed hypersensitivity reaction after hyaluronic acid filler (VCY-20).

Hyaluronic acid (HA) filler, a transient injectable used for rejuvenating facial treatments, has become increasingly popular over time since it doesn't require surgery. Although these procedures are generally safe, there are some application-related complications. These issues fall into three categories: reactions with early, delayed, or late onset. This case report features a 55-year-old female patient who developed widespread facial edema as a result of a delayed hypersensitivity reaction that happened after HA filler was applied.

Human Neural Stem Cell Expansion in Natural Polymer Scaffolds Under Chemically Defined Condition.

The maintenance and expansion of human neural stem cells (hNSCs) in 3D tissue scaffolds is a promising strategy in producing cost-effective hNSCs with quality and quantity applicable for clinical applications. A few biopolymers have been extensively used to fabricate 3D scaffolds, including hyaluronic acid, collagen, alginate, and chitosan, due to their bioactive nature and availability. However, these polymers are usually applied in combination with other biomolecules, leading to their responses difficult to ascribe to. Here, scaffolds made of chitosan, alginate, hyaluronic acid, or collagen, are explored for hNSC expansion under xeno-free and chemically defined conditions and compared for hNSC multipotency maintenance. This study shows that the scaffolds made of pure chitosan support the highest adhesion and growth of hNSCs, yielding the most viable cells with NSC marker protein expression. In contrast, the presence of alginate, hyaluronic acid, or collagen induces differentiation toward immature neurons and astrocytes even in the maintenance medium and absence of differentiation factors. The cells in pure chitosan scaffolds preserve the level of transmembrane protein profile similar to that of standard culture. These findings point to the potential of using pure chitosan scaffolds as a base scaffolding material for hNSC expansion in 3D.

Cadmium nanocluster as a safe nanocarrier: biodistribution in BALB/c mice and application to carry crocin to breast cancer cell lines.

Aim: Metal nanoclusters are emerging nanomaterials applicable for drug delivery. Here, the toxicity and oxidative stress induction of divalent cationic cadmium (Cd2+) was compared with a Cd in the form of nanocluster. Then, it was used for targeted drug delivery into breast cancer cell lines. Methods: Using a green chemistry route, a Cd nanocluster (Cd-NC) was synthesized based on bovine serum albumin. After characterization, its genotoxicity and oxidative stress induction were studied in both in vitro and in vivo. After that, it was conjugated with hyaluronic acid (HA). The efficiency of hyaloronized-Cd-CN (HA-Cd-NC) for loading and releasing crocin (Cro), an anticancer phytochemical, was studied. Finally, it was applied for cell death induction in a panel of breast cancer cell lines. Results: The comet assay results indicated that, unlike Cd2+ and potassium permanganate (KMnO4), no genotoxicity and oxidative stress was induced by Cd-NC in vitro. Then, the pharmacokinetics of this Cd-NC was studied in vivo. The data showed that Cd-NC has accumulated in the liver and excreted from the feces of mice. Unlike Cd2+, no toxicity and oxidative stress were induced by this Cd-NC in animal tissues. Then, the Cd-NC was targeted toward breast cancer cells by adding HA, a ligand for the CD44 cell surface receptor. After that, Cro was loaded on HA-Cd-NC and it was used for the treatment of a panel of human breast cancer cell lines with varying degrees of CD44. The half-maximal drug inhibitory concentration (IC50) of Cro was significantly decreased when it was loaded on HA-Cd-NC, especially in MDA-MB-468 with a higher degree of CD44 at the surface. These results indicate the higher toxicity of Cro toward breast cancers when carried out by HA-Cd-NC. Conclusions: The Cd-NC was completely safe and is a promising candidate for delivering anticancer drugs/phytochemicals into the targeted breast tumors.

Co-delivery of oncolytic virus and chemotherapeutic modality: Vincristine against prostate cancer treatment: A potent viro-chemotherapeutic approach.

Prostate cancer is a prevalent carcinoma among males, and conventional treatment options are often limited. Cytotoxic chemotherapy, despite its drawbacks, remains a mainstay. We propose a targeted co-delivery approach using nanoscale delivery units for Oncolytic measles virus (OMV) and vincristine (VC) to enhance treatment efficacy. The HA-coated OMV + VC-loaded TCs nanoformulation is designed for targeted oncolytic activity in prostate cancer. The CD44 expression analysis in prostate cancer cell lines indicates a significantly high expression in PC3 cells. The optimization of nanoformulations using Design of Expert (DOE) is performed, and the preparation and characterization of HA-coated OMV + VC-loaded TCs nanoformulations are detailed showing average particle size 397.2 ± 0.01 nm and polydispersity index 0.122 with zeta potential 19.7 + 0.01 mV. Results demonstrate successful encapsulation efficiency with 2.4 × 106 TCID50/Ml and sustained release of OMV and VC from the nanoformulation for up to 72 h. In vitro, assays reveal potent anticancer activity at 10 ± 0.71% cell viability in PC3 cells compared to 73 ± 0.66% in HPrEC and significant morphological changes at 90 µg/ml in dose and time-dependent manner. The co-formulation showed positive cell death 49.5 ± 0.02% at 50 µg PI/ml in PBS and 54.3% cell cycle arrest at the G2/M phase, 8.1% G0/G1 and 5.7% at S phase, with significant mitochondrial membrane potential (MMP) at 50 µg/ml, as assessed by flow cytometry (FACS). The surface-integrating ligand approach enhances the targeted delivery of the oncolytic virus and chemotherapeutic drug, presenting a potential alternative for prostate cancer treatment and suggested that co-administering VC and OMV in a nanoformulation could improve therapeutic outcomes while reducing chemotherapeutic drug doses.

Visible light photo-crosslinking of biomimetic gelatin-hyaluronic acid hydrogels for adipose tissue engineering.

Tissue engineering (TE) of adipose tissue (AT) is a promising strategy that can provide 3D constructs to be used for in vitro modelling, overcoming the limitations of 2D cell cultures by closely replicating the complex breast tissue extracellular matrix (ECM), cell-cell, and cell-ECM interactions. However, the challenge in developing 3D constructs of AT resides in designing artificial matrices that can mimic the structural properties of native AT and support adipocytes biological functions. Herein, we developed photocrosslinkable hydrogels by employing gelatin methacrylate (GelMA) and hyaluronic acid methacrylate (HAMA) to mimic the collagenous and glycosaminoglycan components of AT microenvironment, respectively. The physico-mechanical properties of the hydrogels were tuned to target AT biomimetic properties by varying the hydrogel formulation (with or without hyaluronic acid), and the amount of photoinitiator (ruthenium/sodium persulfate) used to crosslink the hydrogels via visible light. The physical and mechanical properties of the developed hydrogels were tuned by varying the material formulation and the photoinitiator concentration. Preadipocytes were encapsulated inside the hydrogels and differentiated into mature adipocytes. Findings enlightened that HAMA addition in hybrid hydrogels boosted an increased lipid accumulation. The engineered biomimetic adipocyte-based constructs resulted promising as scaffolds or 3D in vitro models of AT.