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Sustainable biomaterials are essential for advancing tissue engineering. This study investigates the in vivo biocompatibility and regenerative potential of seaweed cellulose (SC) scaffolds derived from Ulva sp. and Cladophora sp. as connective support matrices. SC scaffolds were fabricated using an optimized decellularization process that preserved their distinct porous ( Ulva ) and fibrous ( Cladophora ) architectures. Subcutaneous implantation in Sprague–Dawley rats demonstrated minimal foreign body response and successful integration over an eight-week period. Histological analysis revealed architecture-driven healing dynamics: Ulva sp. scaffolds promoted compartmentalized healing, characterized by distributed vascularized connective tissue, while Cladophora sp. scaffolds supported stratified tissue organization with aligned collagen deposition. Both scaffolds exhibited progressive vascularization and reduced foreign body response, with no adverse inflammatory reactions observed. These findings highlight the potential of SC scaffolds for regenerative applications that require tailored tissue responses, while their renewable, marine- origin underscores their potential as sustainable biomaterials in advanced healthcare solutions.

Anterior cruciate ligament reconstruction (ACLR) is one of the more common procedures performed worldwide and perhaps the most widely studied construct in orthopedic literature. Interference screws are reliable and frequently used for ligament reconstruction, providing rigid fixation and facilitates graft incorporation allowing for the physiologic loads of early rehabilitation. The purpose of this study was to determine the bio-integration profile and quality of soft tissue graft when using mineral fiber-reinforced screws in an ACLR interference model. Nine sheep underwent ACLR using harvested autologous tendon graft fixated with 4.75 mm screws made of continuous mineral fibers. Histopathology and imaging evaluation at 28, 52, 104, 132-weeks (W) demonstrated mesenchymal tissue ingrowth into implant wall at 28 W, which increased at 52 W and peaked at 104 W. At 132 W, implants fully replaced by newly remodeled bone. Graft cellularity was evident at 28 W and continued to increase through 132 W as the tendon ossified at sites of bone contact. Pro-healing M2-macrophages and giant cells remained infrequent, with minor increases between 52 W and 104 W, attributed to expected phagocytic response. Pro-inflammatory cells (i.e., M1-macrophages, polymorphonuclears) were absent through the entire study course. In conclusion, bio-integrative screws provide secure soft tissue fixation with replacement by bone demonstrating graft cellularization over time.

Background Thermal damage during surgical procedures is a critical factor influencing patient safety and outcomes, particularly in minimally invasive laparoscopic surgeries. Advanced robotic-assisted surgical systems, such as the Anovo ® Surgical System, incorporate monopolar electrosurgical tools designed to optimize precision while minimizing collateral tissue damage. This study evaluates the thermal effects of the Anovo ® Hook Electrode and Curved Scissors compared to conventional off-the-shelf (OTS) tools. Methods An ex vivo study was conducted using 288 tissue samples from a swine model, including liver, kidney, and muscle tissues. Thermal effects during monopolar cutting and coagulation were evaluated at three power settings (low, medium, high) and durations (5, 10, 15 s). Histological analysis was performed on all samples to assess coagulation necrosis and thermal spread. Statistical equivalence testing was applied to compare the Anovo ® devices with OTS tools. Results The Anovo ® devices achieved precise and consistent thermal effects, meeting equivalence criteria in 97.57% of samples. Histological analysis confirmed well-defined coagulation zones with no unintended necrosis beyond the treated areas. Thermal spread increased proportionally with power settings and activation durations, but remained within clinically acceptable limits. The Anovo ® devices demonstrated performance comparable to, and occasionally superior to, OTS tools. Conclusion The Anovo ® Hook Electrode and Curved Scissors provide safe and effective monopolar electrosurgical performance with precise thermal effects. These findings support their use in robotic-assisted laparoscopic surgeries and highlight their potential to enhance surgical precision and patient outcomes.

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused predominantly by immune dysregulation. The global impact of AD continues to increase, making it not only a significant public health issue but also a risk factor for progression into other allergic phenotype disorders. Treatment of moderate-to-severe symptomatic AD involves general skin care, restoration of the skin barrier function, and local anti-inflammatory drug combinations, and may also require systemic therapy, which is often associated with severe adverse effects and is occasionally unsuitable for long-term use. The main objective of this study was to develop a new delivery system for AD treatment based on dissolvable microneedles containing dexamethasone incorporated in a dissolvable polyvinyl alcohol/polyvinylpyrrolidone matrix. SEM imaging of the microneedles showed well-structured arrays comprising pyramidal needles, fast drug release in vitro in Franz diffusion cells, an appropriate mechanical strength recorded with a texture analyzer, and low cytotoxicity. Significant clinical improvements, including in the dermatitis score, spleen weights, and clinical scores, were observed in an AD in vivo model using BALB/c nude mice. Taken together, our results support the hypothesis that microneedle devices loaded with dexamethasone have great potential as a treatment for AD and possibly for other skin conditions as well.

Background: Venous sinus stenting is a promising treatment for intracranial venous disorders, such as idiopathic intracranial hypertension and pulsatile tinnitus, associated with transverse sinus stenosis. The VIVA Stent System (VSS) is a novel self-expanding braided venous stent designed to navigate tortuous cerebral venous anatomy. This preclinical study assessed the safety, thrombogenicity, and performance of the VSS in a swine model. Methods: Fifteen swine underwent bilateral internal mammary vein stenting with either the VSS (n = 9) or the PRECISE® PRO RX stent (n = 6, reference). Fluoroscopy and thrombogenicity assessments were conducted on the day of stenting, clinical pathology analysis was carried out throughout the in-life phase, and CT Venography was performed before sacrifice. Animals were sacrificed at 30 ± 3 or 180 ± 11 days post-stenting for necropsy and histological evaluation. Results: Fluoroscopic angiography confirmed the successful VSS deployment with complete venous wall apposition and no vessel damage. The VSS achieved the highest scores on a four-point Likert scale for most performance parameters. No thrombus formation was observed on either delivery system. CT Venography confirmed vessel patency, no stent migration, and complete stent integrity. Histopathology showed a mild, expected foreign body reaction at 30 days, which resolved by 180 days, indicating normal healing progression. Both stents showed increased luminal diameter and decreased wall thickness at 180 days, suggesting vessel recovery. No adverse reactions were observed in non-target organs. Conclusions: The VSS exhibited favorable safety, procedural performance, and thromboresistance in a swine model, supporting its potential clinical use for treating transverse sinus stenosis and related conditions.

Category: Basic Sciences/Biologics Introduction/Purpose: Injuries to weight-bearing bones can be detrimental to patient mobility, often requiring surgical intervention, as mechanical failure leads to non-union, joint stiffness, and compromised function. Metal implants are widely used for fracture fixation; however, stress concentration, irritation, and pain often result in hardware removal, driving the development of non-permanent implants, traditionally polymer-based. These, in turn, lack strength and may cause adverse inflammatory reactions. Thus, an unmet need exists for more robust, safely eliminated fixation devices. This study aimed to evaluate the performance of bio-integrative, mineral fiber-reinforced screws, currently utilized for multiple surgical procedures in Orthopedic Foot and Ankle Surgery, in an in vivo fully load-bearing distal femur fracture model in sheep. Methods: Five sheep were subjected to femur lateral condyle osteotomy. Fixation was performed using two 3.5mm fiber-reinforced compression screws made of mineral fibers comprised of elements found in native bone, bound by PLDLA [poly (L-lactide-co- D, L-lactide)]. Animals recovered to full load-bearing conditions. Micro CT and histopathology were performed at 26, 78, 104, and 130 weeks (W). Osteotomy healing, new bone formation, tissue ingrowth into the implant wall, and biocompatibility measures were evaluated. Results: All animals demonstrated uneventful recovery. Stable reduction was evident by optimal bone healing on imaging and histological evaluation. At 12 weeks, all sites demonstrated anatomical alignment and complete bone bridging across osteotomy sites, with no implant failure. Cellular response was dominated by anti-inflammatory M2 macrophages and multinucleated giant cells associated with the expected phagocytic response. Implant bio-integration was completed by 130W, with no material remaining and no adverse effects. Conclusion: Large animal models are considered benchmarks for the long-term effects of orthopedic implants due to their similarity to humans with respect to bone composition, dimensions, physiology, biomechanics, and remodeling. This fully load-bearing femoral osteotomy sheep model demonstrates the safe and effective use of bio-integrative implant technology, suggesting its applicability in various orthopedic foot and ankle indications.

Background Saroglitazar is a novel PPAR-α/γ agonist with predominant PPAR-α activity. In various preclinical models, saroglitazar has been shown to prevent & reverse symptoms of NASH. In view of these observations, and the fact that NASH is a progressive disease leading to HCC, we hypothesized that saroglitazar may prevent the development of HCC in rodents. Methods HCC was induced in C57BL/6 mice by a single intraperitoneal injection of 25 mg/kg diethylnitrosamine (DEN) at the age of 4 weeks and then feeding the animal a choline-deficient, L-amino acid- defined, high-fat diet (CDAHFD) for the entire study duration. Eight weeks after initiation of CDAHFD, saroglitazar (1 and 3 mg/kg) treatment was started and continued for another 27 weeks. Results Saroglitazar treatment significantly reduced the liver injury markers (serum ALT and AST), reversed hepatic steatosis and decreased the levels of pro-inflammatory cytokines like TNF-α in liver. It also resulted in a marked increase in serum adiponectin and osteopontin levels. All disease control animals showed hepatic tumors, which was absent in saroglitazar (3 mg/kg)- treatment group indicating 100% prevention of hepatic tumorigenesis. This is the first study demonstrating a potent PPARα agonist causing suppression of liver tumors in rodents, perhaps due to a strong anti-NASH activity of Saroglitazar that overrides its rodent-specific peroxisome proliferation activity. Conclusion The data reveals potential of saroglitazar for chemoprevention of hepatocellular carcinoma in patients with NAFLD/NASH.

viability assays are essential in drug discovery, development, and pharmacovigilance. However, traditional methods for evaluating cell viability rely on destructive processes that render cultures non-viable, limiting them to single endpoint measurements and precluding further analyses. We present Neural Viability Regression (NViR), a deep learning-based method that enables real-time, non-invasive quantification of culture viability from microscopy images. Although developed and validated on liver spheroids, the framework includes a retrainable pipeline adaptable to other spheroid types. To demonstrate its applicability, we exposed human liver spheroids to 108 FDA-approved drugs and captured microscopy images over time, using NViR's viability estimates to predict Drug-Induced Liver Injury (DILI). NViR's viability assessments accurately predicted whether a drug induces DILI in humans. Its non-invasive nature enabled frequent viability evaluations throughout experiments, capturing subtle temporal changes while preserving the structural integrity of the cultures and substantially reducing both culture and labor costs. The cost-effectiveness and non-destructive characteristics of NViR enable high-frequency, high-throughput viability assessments, positioning it as a tool to enhance liver safety protocols and reduce both the costs and failure rates in drug discovery and development.

Background Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which often includes obesity, diabetes, and dyslipidemia. Several studies in mice and humans have implicated the involvement of the gut microbiome in NAFLD. While cannabis and its phytocannabinoids may potentially be beneficial for treating metabolic disorders such as NAFLD, their effects on liver diseases and gut microbiota profile have yet to be addressed. In this study, we evaluated the therapeutic effects of the two major cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), on NAFLD progression. Methods NAFLD was induced by feeding mice a high fat-cholesterol diet (HFCD) for 6 weeks. During this period, the individual cannabinoids, THC or CBD, were added to the experimental diets at a concentration of 2.5 or 2.39 mg/kg. Profile of lipids, liver enzymes, glucose tolerance, and gene expression related to carbohydrate lipids metabolism and liver inflammation was analyzed. The effect of THC or CBD on microbiota composition in the gut was evaluated. Results While not alleviating hepatic steatosis, THC or CBD treatment influenced a number of parameters in the HFCD mouse model. CBD increased food intake, improved glucose tolerance, reduced some of the inflammatory response including TNFa and iNOS, and partially mitigated the microbiome dysbiosis observed in the HFCD fed mice. THC produced a much weaker response, only slightly reducing inflammatory-related gene expression and microbiome dysbiosis. Conclusions The results of this study indicate the potential therapeutic effects of individual phytocannabinoids are different from the effects of the cannabis plant possessing a mixture of compounds. While CBD may help ameliorate symptoms of NAFLD, THC alone may not be as effective. This disparity can putatively be explained based on changes in the gut microbiota.

Disruption of the reprogrammed energy management system of malignant cells is a prioritized goal of targeted cancer therapy. Two regulators of this system are the Fer kinase, and its cancer cell specific variant, FerT, both residing in subcellular compartments including the mitochondrial electron transport chain. Here, we show that a newly developed inhibitor of Fer and FerT, E260, selectively evokes metabolic stress in cancer cells by imposing mitochondrial dysfunction and deformation, and onset of energy-consuming autophagy which decreases the cellular ATP level. Notably, Fer was also found to associate with PARP-1 and E260 disrupted this association thereby leading to PARP-1 activation. The cooperative intervention with these metabolic pathways leads to energy crisis and necrotic death in malignant, but not in normal human cells, and to the suppression of tumors growth in vivo. Thus, E260 is a new anti-cancer agent which imposes metabolic stress and cellular death in cancer cells. The tyrosine-kinases Fer/FerT associate with the mitochondrial electron transport chain in cancer cells supporting their metabolic reprogramming. Here the authors discover a compound that disrupts Fer /FerT activity and selectively induces cell death of cancer cell lines displaying anti-tumor activity in vivo.