Development of an injectable oxidized dextran/gelatin hydrogel capable of promoting the healing of alkali burn-associated corneal wounds.

The cornea serves as an essential shield that protects the underlying eye from external conditions, yet it remains highly vulnerable to injuries that could lead to blindness and scarring if not promptly and effectively treated. Excessive inflammatory response constitute the primary cause of pathological corneal injury. This study aimed to develop effective approaches for enabling the functional repair of corneal injuries by combining nanoparticles loaded with anti-inflammatory agents and an injectable oxidized dextran/gelatin/borax hydrogel. The injectability and self-healing properties of developed hydrogels based on borate ester bonds and dynamic Schiff base bonds were excellent, improving the retention of administered drugs on the ocular surface. In vitro cellular assays and in vivo animal studies collectively substantiated the proficiency of probucol nanoparticle-loaded hydrogels to readily suppress proinflammatory marker expression and to induce the upregulation of anti-inflammatory mediators, thereby supporting rapid repair of rat corneal tissue following alkali burn-induced injury. As such, probucol nanoparticle-loaded hydrogels represent a prospective avenue to developing long-acting and efficacious therapies for ophthalmic diseases.

Autophagy inhibition mediated via an injectable and NO-releasing hydrogel for amplifying the antitumor efficacy of mild magnetic hyperthermia.

While mild hyperthermia holds great potential in the treatment of solid tumors, the thermal stress-triggered self-repairing autophagy significantly compromises its efficacy. To circumvent this obstacle, an injectable hydrogel (NO-Gel) composed of thermosensitive poly(ethylene glycol)-polypeptide copolymers modified with abundant NO donors on their side chains is developed. Meanwhile, ferrimagnetic Zn0.5Fe2.5O4 magnetic nanoparticles (MNPs) with high magnetic-heat conversion efficiency are synthesized and loaded into NO-Gel to obtain MNPs@NO-Gel. The MNPs@NO-Gel system exhibits a sol-gel transition upon heating, and has the ability to perform multiple magnetic hyperthermia therapy (MHT) after only one administration due to the even distribution and strong immobilization of MNPs in NO-Gel. NO can be continuously liberated from NO-Gel and this process is markedly accelerated by MHT. Additionally, MNPs@NO-Gel maintains its integrity in vivo for over one month and the released MNPs are metabolized by the spleen. After a single administration of MNPs@NO-Gel at the tumor site, three mild MHT treatments with similar effects are fulfilled, and the sufficient supply of NO effectively inhibits MHT-induced autophagic flux via blocking the formation of autophagosomes and synchronously destroying lysosomes, thereby substantially boosting the efficacy of mild MHT. As a consequence, CT-26 colon tumors are completely eliminated without causing severe side-effects.

LAI-ART Awareness, Willingness, Barriers and Facilitators among Black Sexual Minority Men Living with HIV in the US South.

Black sexual minority men (BSMM) continue to bear a disproportionate burden of HIV in the United States, with the highest incidence and prevalence in the southern region of the country. In Texas, BSMM living with HIV (BSMM+) have the lowest rates of viral suppression of all SMM and have lower antiretroviral treatment (ART) adherence than white and Hispanic SMM. Long-acting injectable ART (LAI-ART) can potentially overcome several barriers to daily oral ART adherence (e.g., stigma, forgetfulness, pill fatigue). However, little is known about the knowledge, willingness, barriers, and facilitators regarding LAI-ART among BSMM+. From July 2022 to September 2023, we conducted in-depth, semi-structured interviews with 27 BSMM+ from the Houston and Dallas Metropolitan Areas, Texas. Data were analyzed using a thematic analysis approach. Most men knew about LAI-ART, but their understanding varied based on their existing sources of information. Some men were enthusiastic, some were cautious, and some reported no interest in LAI-ART. Barriers to LAI-ART included a lack of public insurance coverage of LAI-ART; fear of needles and side effects; the frequency of injection visits; the requirement of viral suppression before switching from oral ART to LAI-ART; and satisfaction with oral daily ART. Motivators of LAI-ART uptake included the eliminated burden of daily pills and reduced anxiety about possibly missing doses. BSMM+ may be among those who could most benefit from LAI-ART, though more research is needed to understand which factors influence their willingness and how the barriers to LAI-ART might be addressed, particularly among diverse communities of SMM of color.

Development and Evaluation of a Water-Free In Situ Depot Gel Formulation for Long-Acting and Stable Delivery of Peptide Drug ACTY116.

In situ depot gel is a type of polymeric long-acting injectable (pLAI) drug delivery system; compared to microsphere technology, its preparation process is simpler and more conducive to industrialization. To ensure the chemical stability of peptide ACTY116, we avoided the use of harsh conditions such as high temperatures, high shear mixing, or homogenization; maintaining a water-free and oxygen-free environment was also critical to prevent hydrolysis and oxidation. Molecular dynamics (MDs) simulations were employed to assess the stability mechanism between ACTY116 and the pLAI system. The initial structure of ACTY116 with an alpha helix conformation was constructed using SYBYL-X, and the copolymer PLGA was generated by AMBER 16; results showed that PLGA-based in situ depot gel improved conformational stability of ACTY116 through hydrogen bonds formed between peptide ACTY116 and the components of the pLAI formulation, while PLGA (Poly(DL-lactide-co-glycolide)) also created steric hindrance and shielding effects to prevent conformational changes. As a result, the chemical and conformational stability and in vivo long-acting characteristics of ACTY116 ensure its enhanced efficacy. In summary, we successfully achieved our objective of developing a highly stable peptide-loaded long-acting injectable (LAI) in situ depot gel formulation that is stable for at least 3 months under harsh conditions (40 °C, above body temperature), elucidating the underlying stabilisation mechanism, and the high stability of the ACTY116 pLAI formulation creates favourable conditions for its in vivo pharmacological activity lasting for weeks or even months.

Synchronized Codelivery of Combination Chemotherapies Intratumorally Using a Lipidic Lyotropic Liquid Crystal System.

In this work, an injectable in situ depot-forming lipidic lyotropic liquid crystal (L3C) system is developed to codeliver a precisely synchronized combination of chemotherapeutics intratumorally. The developed L3C system is composed of amphiphilic lipids and surfactants, including monoolein, phosphatidylcholine, tocopherol acetate, and d-α-tocopherol polyethylene glycol 1000 succinate. Owing to its amphiphilic nature, the developed formulation can coaccommodate both hydrophobic and hydrophilic chemotherapeutic moieties simultaneously. The study presents a proof of concept by designing a combination chemotherapy regimen in vitro and demonstrating its in vivo translation using doxorubicin and paclitaxel as model hydrophilic and hydrophobic drug moieties, respectively. The synchronized combination of the two chemotherapeutics with maximum synergistic activity was identified, coloaded in the developed L3C system at predefined stoichiometric ratios, and evaluated for antitumor efficacy in the 4T1 breast tumor model in BALB/c mice. The drug-loaded L3C formulation is a low-viscosity injectable fluid with a lamellar phase that transforms into a hexagonal mesophase depot system upon intratumoral injection. The drug-loaded depot system locally provides sustained intratumoral delivery of the chemotherapeutics combination at their precisely synchronized ratio for over a period of one month. Results demonstrate that the exposure of the tumor to the precisely synchronized intratumoral chemotherapeutics combination via the developed L3C system resulted in significantly higher antitumor activity and reduced cardiotoxicity compared to the unsynchronized combination chemotherapy or the synchronized but uncoordinated drug delivery administered by a conventional intravenous route. These findings demonstrate the potential of the developed L3C system for achieving synchronized codelivery of the chemotherapeutics combination intratumorally and improving the efficacy of combination chemotherapy.

Injectable and in situ foaming shape-adaptive porous Bio-based polyurethane scaffold used for cartilage regeneration.

Irregular articular cartilage injury is a common type of joint trauma, often resulting from intense impacts and other factors that lead to irregularly shaped wounds, the limited regenerative capacity of cartilage and the mismatched shape of the scaffods have contributed to unsatisfactory therapeutic outcomes. While injectable materials are a traditional solution to adapt to irregular cartilage defects, they have limitations, and injectable materials often lack the porous microstructures favorable for the rapid proliferation of cartilage cells. In this study, an injectable porous polyurethane scaffold named PU-BDO-Gelatin-Foam (PUBGF) was prepared. After injection into cartilage defects, PUBGF forms in situ at the site of the defect and exhibits a dynamic microstructure during the initial two weeks. This dynamic microstructure endows the scaffold with the ability to retain substances within its interior, thereby enhancing its capacity to promote chondrogenesis. Furthermore, the chondral repair efficacy of PUBGF was validated by directly injecting it into rat articular cartilage injury sites. The injectable PUBGF scaffold demonstrates a superior potential for promoting the repair of cartilage defects when compared to traditional porous polyurethane scaffolds. The substance retention ability of this injectable porous scaffold makes it a promising option for clinical applications.

Healthcare professionals' perspectives on use of PCSK9 inhibitors in cardiovascular disease: an in-depth qualitative study.

AIM: Injectable medicines such as PCSK-9 inhibitors are increasingly used to manage risk factors for cardiovascular events with little information around the perceptions of healthcare professionals (HCPs) on the administrative and clinical practicalities. The aim was to identify the facilitators and barriers on the use of injectable therapies with CV benefits through interviews with HCPs. METHODS AND RESULTS: Qualitative interviews were conducted in the United Kingdom (London and Leeds) and Italy (Rome and Milan) in 2021. Coding was undertaken using NVivo and thematic analysis performed. A total of 38 HCPs were interviewed, 19 in each country composing of physicians (n = 18), pharmacists (n = 10), nurses (n = 9) and pharmacy technician (n = 1). Four themes emerged: (i) Clinicians' previous experiences with injectable therapies (ii) Challenges with patients' behaviours and beliefs (iii) Clinicians' knowledge of injectable therapies and therapeutic inertia and (iv) Organisational and governance issues. The behaviour and beliefs from healthcare professionals focused on facilitating behaviour change as well as the poor interdisciplinary working and collaboration. Therapeutic inertia was raised where physicians either lacked awareness of injectable therapies or were unwilling to prescribe them. The importance of facilitating patient education on injection techniques was highlighted while organisational and governance issues identified the lack of guidance to inform practice. Clear pathways are required to identify those who were eligible for injectable therapies as well as on how injectables should be prescribed. CONCLUSION: If medicine optimisation is to be achieved, there needs to be structured processes in place to identify eligible patients and the development of educational material.

Local Application of Tanshinone IIA protects mesenchymal stem cells from apoptosis and promotes fracture healing in ovariectomized mice.

BACKGROUND: Elderly patients suffering from osteoporotic fractures are more susceptible to delayed union or nonunion, and their bodies then are in a state of low-grade chronic inflammation with decreased antioxidant capacity. Tanshinone IIA is widely used in treating cardiovascular and cerebrovascular diseases in China and has anti-inflammatory and antioxidant effects. We aimed to observe the antioxidant effects of Tanshinone IIA on mesenchymal stem cells (MSCs), which play important roles in bone repair, and the effects of local application of Tanshinone IIA using an injectable biodegradable hydrogel on osteoporotic fracture healing. METHODS: MSCs were pretreated with or without different concentrations of Tanshinone IIA followed by H2O2 treatment. Ovariectomized (OVX) C57BL/6 mice received a mid-shaft transverse osteotomy fracture on the left tibia, and Tanshinone IIA was applied to the fracture site using an injectable hydrogel. RESULTS: Tanshinone IIA pretreatment promoted the expression of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes, and inhibited H2O2-induced reactive oxygen species accumulation in MSCs. Furthermore, Tanshinone IIA reversed H2O2-induced apoptosis and decrease in osteogenic differentiation in MSCs. After 4 weeks of treatment with Tanshinone IIA in OVX mice, the bone mineral density of the callus was significantly increased and the biomechanical properties of the healed tibias were improved. Cell apoptosis was decreased and Nrf2 expression was increased in the early stage of callus formation. CONCLUSIONS: Taken together, these results indicate that Tanshinone IIA can activate antioxidant enzymes to protect MSCs from H2O2-induced cell apoptosis and osteogenic differentiation inhibition. Local application of Tanshinone IIA accelerates fracture healing in ovariectomized mice.

HPTN 083-02: factors influencing adherence to injectable PrEP and retention in an injectable PrEP study.

INTRODUCTION: HPTN 083 demonstrated the superiority of long-acting cabotegravir (CAB-LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as pre-exposure prophylaxis (PrEP) among cisgender men and transgender women who have sex with men (MSM/TGW). HPTN 083 provided the first opportunity to understand experiences with injectable PrEP in a clinical trial. METHODS: Participants from two US sites (Chicago, IL and Atlanta, GA) and one international site (Rio de Janeiro, Brazil) were purposively sampled for individual qualitative interviews (N = 40), between November 2019 and March 2020, to explore trial experiences, barriers to adherence and other factors that may have impacted study implementation or outcomes. The blinded phase ended early due to efficacy; this analysis includes interviews conducted prior to unblinding with three groups defined by adherence (i.e. injection visit attendance): adherent (n = 27), non-adherent (n = 12) and early discontinuers (n = 1). Data were organized using NVivo software and analysed using content analysis. RESULTS: Participants (mean age: 27) were primarily cisgender MSM (90%) and Black/African American (60%). Reasons for trial enrolment and PrEP use included a preference for using HIV prevention medication versus treatment in the event of HIV acquisition; the ability to enhance health via study-related education and services; access to a novel, convenient HIV prevention product at no cost; and contributing to MSM/TGW communities through research. Participants contrasted positive experiences with study staff with their routine clinical care, and emphasized increased scheduling flexibility, thorough communication, non-judgemental counselling and open, affirming environments (e.g. compassion, less stigma) as adherence facilitators. Injection experiences were positive overall; some described early injection-related anxiety, which abated with time and when given some measure of control (e.g. pre-injection countdown), and minimal injection site discomfort. Some concerns and misperceptions about injectable PrEP were reported. Barriers to adherence, across all adherence categories, included structural factors (e.g. financial constraints, travel) and competing demands (e.g. work schedules). CONCLUSIONS: Respondents viewed injectable PrEP trial participation as a positive experience and a means of enhancing wellbeing. Study site flexibility and affirming clinic environments, inclusive of non-judgemental counselling, were key facilitators of adherence. To support injection persistence, interventions that address structural barriers and promote flexible means of injection delivery may be most effective.

Rheological and Injectability Evaluation of Sterilized Poloxamer-407-Based Hydrogels Containing Docetaxel-Loaded Lipid Nanoparticles.

Nanostructured lipid carriers (NLCs) have the potential to increase the bioavailability and reduce the side effects of docetaxel (DTX). However, only a small fraction of nanoparticles given intravenously can reach a solid tumor. In situ-forming gels combined with nanoparticles facilitate local administration and promote drug retention at the tumor site. Injectable hydrogels based on poloxamer 407 are excellent candidates for this hybrid nanoparticle-hydrogel system because of their thermoresponsive behavior and biocompatibility. Therefore, this work aimed to develop injectable poloxamer hydrogels containing NLCs for intratumoral delivery of DTX. To ensure sterility, the obtained hydrogels were autoclaved (121 °C for 15 min) after preparation. Then, the incorporation of NLCs into the poloxamer hydrogels and the impact of steam sterilization on the nanocomposite hydrogels were evaluated concerning sol-gel transition, injectability, and physicochemical stability. All formulations were extruded through the tested syringe-needle systems with acceptable force (2.2-13.4 N) and work (49.5-317.7 N·mm) of injection. Following steam sterilization, injection became easier in most cases, and the physicochemical properties of all hydrogels remained practically unchanged according to the spectroscopical and thermal analysis. The rheological evaluation revealed that the nanocomposite hydrogels were liquid at 25 °C and underwent rapid gelation at 37 °C. However, their sterilized counterparts gelled at 1-2 °C above body temperature, suggesting that the autoclaving conditions employed had rendered these nanocomposite hydrogels unsuitable for local drug delivery.

Bone Regenerative Effect of Injectable Hypoxia Preconditioned Serum-Fibrin (HPS-F) in an Ex Vivo Bone Defect Model.

Biofunctionalized hydrogels are widely used in tissue engineering for bone repair. This study examines the bone regenerative effect of the blood-derived growth factor preparation of Hypoxia Preconditioned Serum (HPS) and its fibrin-hydrogel formulation (HPS-F) on drilled defects in embryonic day 19 chick femurs. Measurements of bone-related growth factors in HPS reveal significant elevations of Osteopontin, Osteoprotegerin, and soluble-RANKL compared with normal serum (NS) but no detection of BMP-2/7 or Osteocalcin. Growth factor releases from HPS-F are measurable for at least 7 days. Culturing drilled femurs organotypically on a liquid/gas interface with HPS media supplementation for 10 days demonstrates a 34.6% increase in bone volume and a 52.02% increase in bone mineral density (BMD) within the defect area, which are significantly higher than NS and a basal-media-control, as determined by microcomputed tomography. HPS-F-injected femur defects implanted on a chorioallantoic membrane (CAM) for 7 days exhibit an increase in bone mass of 123.5% and an increase in BMD of 215.2%, which are significantly higher than normal-serum-fibrin (NS-F) and no treatment. Histology reveals calcification, proteoglycan, and collagen fiber deposition in the defect area of HPS-F-treated femurs. Therefore, HPS-F may offer a promising and accessible therapeutic approach to accelerating bone regeneration by a single injection into the bone defect site.

Reduced emergency department use among insured individuals receiving extended-release buprenorphine in a health system setting.

Introduction: Extended-release buprenorphine (XR-Bup) is associated with reduced opioid use and opioid negative urine drug screens. Little is known about its use in outpatient addiction care provided within health systems. Methods: Individuals prescribed XR-Bup were identified from electronic health records; chart abstraction was conducted. Primary outcome was all-cause emergency department (ED) use. Secondary outcomes included ED use or inpatient stays for mental health or substance use, ED use for any other cause, discontinuation reasons, and drug substitution. Statistical comparisons used nonparametric tests from related samples (McNemar's test and Wilcoxon matched pair tests) to test outcomes six months prior and 6 months following XR-Bup initiation. Results: 152 individuals had an XR-Bup order, 126 received >1 injection. Among those consistently insured 6 months prior to and following XR-Bup initiation (n=99), the mean number of injections following initiation was 3.95; one-third received 6 doses in the 6 months. The proportion of individuals using ED services for all causes declined (41% prior vs. 28% following XR-Bup initiation, p<.05); similar results were found for secondary ED use outcomes. The proportion of individuals requiring inpatient treatment for mental health or substance use also declined (46% vs. 16%, p<.01). Common reasons for discontinuing XR-Bup included losing insurance (21%) or cost (11%). The most common non-prescribed substances used during treatment were opioids (n=31) and THC (n=20). Conclusions: In this non-randomized retrospective observational study, use of XR-Bup was associated with reduced ED use 6 months following initiation. XR-Bup may help health systems reduce use of costly ED services.

Comparison of long-acting injectable antipsychotics with oral antipsychotics and hospital readmission rates in pediatric patients.

Introduction: Studies indicate that long-acting injectable antipsychotics (LAIAs) reduce the risk of relapse and hospitalization compared with oral antipsychotics (APs) in adults. Oral formulations of APs are well-studied in the pediatric population, but little is known regarding the off-label use of LAIAs in this population. Methods: This retrospective chart review evaluated readmission rates for pediatric patients admitted to a psychiatric ward in a large academic hospital between January 1, 2015, and December 1, 2022, requiring AP therapy. The experimental group included patients initiated on LAIA therapy, and the control group included patients initiated on a new oral AP. Patients were matched by several clinical factors. Results: Each group consisted of 38 patients. For the primary outcome, hospital readmission rates at 3 months, the LAIA group had a 13.2% readmission rate compared with 26.3% in the comparator group (p = .153). In months 4 through 6, there was a 5.3% versus 15.8% readmission rate, respectively (p = .139). In months 7 through 12, it was 7.9% versus 18.4% (p = .179). There were significantly fewer cumulative readmissions at the 1-year mark in the LAIA group (N = 9, 23.7%) compared with the oral AP group (N = 18, 47.4%) (p = .031). No statistically significant differences were seen in hospital length of stay although results numerically favored LAIA. Discussion: In a pediatric population, the administration of an LAIA when compared with the oral equivalent resulted in numerically fewer hospital readmissions, decreased length of stay, and fewer adverse effects, but these effects were not statistically significant except for cumulative readmissions at 1 year.

Injectable and rapidly expandable thrombin-decorated cryogels achieve rapid hemostasis and high survival rates in a swine model of lethal junctional hemorrhage.

Effective therapies are urgently needed to stabilize patients with marginally compressible junctional hemorrhage long enough to get them to the hospital alive. Herein, we report injectable and rapidly expandable cryogels consisting of polyacrylamide and thrombin (AT cryogels) created by cryo-polymerization for the efficient management of lethal junctional hemorrhage in swine. The produced cryogels have small pore sizes and highly interconnected porous architecture with robust mechanical strength. The cryogels exhibit rapid shape memory properties and prove to be resilient against fatigue. These cryogels also show high water/blood absorption capacity, fast blood clotting effect, and enhanced adhesion of red blood cells and platelets in vitro. Further, in vivo, hemostatic efficacy tests in a lethal swine junctional hemorrhage model suggest that treatment with AT cryogels, especially AT-2 cryogels, achieves the least blood loss and the highest survival rate (100 %) compared to currently employed products such as XStat® and combat gauze. The high hemostatic performance of the cryogels may be attributed to highly interconnected porous architecture with small pore size and the use of thrombin as a pro-coagulant agent. Collectively, injectable and rapidly expandable thrombin-decorated polyacrylamide-based cryogels show significant promise as hemostatic material, offering effective management of marginally compressible junctional hemorrhages in prehospital settings.

The mechanical, wear, antibacterial properties and biocompatibility of injectable restorative materials under wet challenge.

OBJECTIVES: To evaluate the mechanical, wear, antibacterial properties, and biocompatibility of injectable composite materials. METHODS: Two injectable composite resins (GU and BI), one flowable composite resin (FS), and one flowable compomer (DF), in A2 shade, were tested. Mechanical properties were tested via three-point bending test immediately after preparation and after 1-day, 7-day, 14-day, and 30-day water storage. Under water-PMMA slurry immersion, specimens were subjected to a 3-body wear test (10,000 cycles) against stainless steel balls, while the roughness, wear depth, and volume loss were recorded. After 1-day and 3-day MC3T3-E1 cell culture, cell viability was evaluated with CCK-8 test kits, while the cell morphology was observed under CLSM and SEM. Antibacterial properties on S. mutans were assessed via CFU counting, CLSM, and SEM observation. SPSS 26.0 was used for statistical analysis (α = 0.05). RESULTS: The mechanical properties were material-dependent and sensitive to water storage. Flexural strength ranked GU > FS > BI > DF at all testing levels. Three nanocomposites had better wear properties than DF. No significant difference on 1-day cell viability was found, but DF showed significantly lower cell proliferation than nanocomposites on 3-day assessment. GU and FS had more favourable cell adhesion and morphology. CFU counting revealed no significant difference, while FS presented a slightly thicker biofilm and BI showed relatively lower bacteria density. CONCLUSIONS: Injectable nanocomposites outperformed the compomer regarding mechanical properties, wear resistance, and biocompatibility. The tested materials presented comparable antibacterial behaviours. Flowable resin-based composites' performances are affected by multiple factors, and their compositions can be attributed. CLINICAL SIGNIFICANCE: A profound understanding of the mechanical, wear, and biological properties of the restorative material is imperative for the clinical success of dental restorations. The current study demonstrated superior properties of highly filled injectable composite resins, which imply their wider indications and better long-term clinical performances.

ECM-mimetic, NSAIDs loaded thermo-responsive, immunomodulatory hydrogel for rheumatoid arthritis treatment.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and it leads to irreversible inflammation in intra-articular joints. Current treatment approaches for RA include non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, and biological agents. To overcome the drug-associated toxicity of conventional therapy and transdermal tissue barrier, an injectable NSAID-loaded hydrogel system was developed and explored its efficacy. RESULTS: The surface morphology and porosity of the hydrogels indicate that they mimic the natural ECM, which is greatly beneficial for tissue healing. Further, NSAIDs, i.e., diclofenac sodium, were loaded into the hydrogel, and the in vitro drug release pattern was found to be burst release for 24 h and subsequently sustainable release of 50% drug up to 10 days. The DPPH assay revealed that the hydrogels have good radical scavenging activity. The biocompatibility study carried out by MTT assay proved good biocompatibility and anti-inflammatory activity of the hydrogels was carried out by gene expression study in RAW 264.7 cells, which indicate the downregulation of several key inflammatory genes such as COX-2, TNF-α & 18s. CONCLUSION: In summary, the proposed ECM-mimetic, thermo-sensitive in situ hydrogels may be utilized for intra-articular inflammation modulation and can be beneficial by reducing the frequency of medication and providing optimum lubrication at intra-articular joints.

Evaluating flexure properties, hardness, roughness and microleakage of high-strength injectable dental composite: an in vitro study.

BACKGROUND: Recently, a new generation of high-strength flowable dental composites has been introduced by manufacturers. The manufacturers claim that these materials have enhanced mechanical and physical properties and are suitable for use in a wide range of direct anterior and posterior restorations, even in high-stress bearing areas. AIM: The objective of this study was to assess certain physical and mechanical properties of these recently introduced high-strength flowable composites in comparison to conventional multipurpose dental composites. METHODS: Four types of high-strength flowable composites (Genial Universal FLO, Gaenial Universal Injectable, Beautifil Injectable, and Beautifil Flow Plus) were tested in experimental groups, while a nanohybrid conventional composite (Filtek Z350 XT) was used as the control. For flexure properties, ten rectangular samples (2 × 2 × 25 mm) were prepared from each composite material and subjected to 5000 cycles of thermocycling. Samples were then subjected to flexural strength testing using the universal testing machine. Another twenty disc-shaped specimens of dimensions (5 mm diameter × 2 mm thickness) were fabricated from each composite material for surface roughness (Ra) (n = 10) and hardness (VHN) test (n = 10). All samples underwent 5000 cycles of thermocycling before testing. Additionally, microleakage testing was conducted on 60 standardized class V cavities prepared on molar teeth and divided randomly into five groups (n = 12). Cavities were then filled with composite according to the manufacturer's instructions and subjected to thermocycling for 1000 cycles before testing using methylene blue solution and a stereomicroscope. RESULTS: All tested materials were comparable to the control group in terms of flexural strength and surface roughness (p > 0.05), with Gaenial Universal FLO exhibiting significantly higher flexural strength compared to the other flowable composite materials tested. However, all tested materials demonstrated significantly lower elastic modulus and surface hardness than the control group (p < 0.05). The control group exhibited higher microleakage scores, while the lowest scores were observed in the Gaenial Universal FLO material (p < 0.05) CONCLUSION: The physical and mechanical behaviors of the different high-strength flowable composites investigated in this study varied. Some of these materials may serve as suitable alternatives to conventional composites in specific applications, emphasizing the importance of dentists being familiar with material properties before making material selections.

Recent Trends in Adipose Tissue-Derived Injectable Therapies for Osteoarthritis: A Scoping Review of Animal Models.

Background and Objectives: This scoping review investigates recent trends in adipose tissue-derived injectable therapies for osteoarthritis (OA) in animal models, focusing on minimally manipulated or lightly processed adipose tissue. By evaluating and examining the specific context in which these therapies were investigated across diverse animal OA models, this review aims to provide valuable insights that will inform and guide future research and clinical applications in the ongoing pursuit of effective treatments for osteoarthritis. Materials and Methods: This research conducted a comprehensive literature review of PubMed and Embase to determine studies about minimally manipulated adipose tissue-derived injectable therapies for osteoarthritis investigated using animal models. The primary search found 530 results. After excluding articles that focused on spontaneous osteoarthritis; on transfected, preconditioned, cultured, or co-cultured adipose-derived stem cells; and articles with unavailable full text, we included 11 articles in our review. Results: The examined therapies encompassed mechanical micro-fragmented adipose tissue (MFAT) and stromal vascular fraction (SVF) obtained via collagenase digestion and centrifugation. These interventions were evaluated across various animal models, including mice, rats, rabbits, and sheep with induced OA. Notably, more studies concentrated on surgically induced OA rather than chemically induced OA. The assessment of these therapies focused on elucidating their protective immunomodulatory, anti-inflammatory, and chondroregenerative potential through comprehensive evaluations, including macroscopic assessments, histological analyses, immunohistochemical examinations, and biochemical assays. Conclusions: This review provides a comprehensive analysis of adipose tissue-derived injectable therapies for osteoarthritis across diverse animal models. While revealing potential benefits and insights, the heterogeneity of data and the limited number of studies highlight the need for further research to formulate conclusive recommendations for clinical applications.

Fibril-Guided Three-Dimensional Assembly of Human Fibroblastic Reticular Cells.

Fibroblastic reticular cells (FRCs) are stromal cells (SCs) that can be isolated from lymph node (LN) biopsies. Studies have shown that these nonhematopoietic cells have the capacity to shape and regulate adaptive immunity and can become a form of personalized cell therapy. Successful translational efforts, however, require the cells to be formulated as injectable units, with their native architecture preserved. The intrinsic reticular organization of FRCs, however, is lost in the monolayer cultures. Organizing FRCs into three-dimensional (3D) clusters would recapitulate their structural and functional attributes. Herein, we report a scaffolding method based on the self-assembling peptide (SAP) EAKII biotinylated at the N-terminus (EAKbt). Cross-linking with avidin transformed the EAKbt fibrils into a dense network of coacervates. The combined forces of fibrillization and bioaffinity interactions in the cross-linked EAKbt likely drove the cells into a cohesive 3D reticula. This facile method of generating clustered FRCs (clFRCs) can be completed within 10 days. In vitro clFRCs attracted the infiltration of T cells and rendered an immunosuppressive milieu in the cocultures. These results demonstrate the potential of clFRCs as a method for stromal cell delivery.

Shaping and shifting schemas on supervised injectable opioid treatment: findings from a cross-sectional qualitative study in two German treatment facilities.

BACKGROUND: Supervised injectable opioid treatment (SIOT) is a promising alternative for people living with opioid use disorder (OUD) who have not sufficiently benefitted from oral opioid substitution treatment. Yet, SIOT utilization remains limited in Germany. We propose that this is due to beliefs, or schemas, on SIOT among people living with OUD. Drawing from medical sociology and social psychology, this study explores the emergence and evolution of such schemas on SIOT. METHODS: We conducted semi-structured interviews with 34 individuals currently in or eligible for SIOT in two German outpatient treatment facilities and paralleled an inductive qualitative content analysis with the exploration of individual cases. RESULTS: The analysis revealed that peer-to-peer interaction and individuals' practical experiences in therapy are crucial in constructing and changing idiosyncratic and shared schemas of SIOT. When facing ambiguous information, cognitive strategies like subtyping served to mitigate uncertainty. CONCLUSION: This research has important practical implications for integrating experiential knowledge into clinical care and improve information sharing among people living with OUD. A nuanced understanding of the complex network of informal advice-seeking and -giving among people living with OUD is indispensable to adequately expand treatment modalities of proven effectiveness.