Bioengineered 3D ovarian model for long-term multiple development of preantral follicle: bridging the gap for poly(ε-caprolactone) (PCL)-based scaffold reproductive applications.

BACKGROUND: Assisted Reproductive Technologies (ARTs) have been validated in human and animal to solve reproductive problems such as infertility, aging, genetic selection/amplification and diseases. The persistent gap in ART biomedical applications lies in recapitulating the early stage of ovarian folliculogenesis, thus providing protocols to drive the large reserve of immature follicles towards the gonadotropin-dependent phase. Tissue engineering is becoming a concrete solution to potentially recapitulate ovarian structure, mostly relying on the use of autologous early follicles on natural or synthetic scaffolds. Based on these premises, the present study has been designed to validate the use of the ovarian bioinspired patterned electrospun fibrous scaffolds fabricated with poly(ε-caprolactone) (PCL) for multiple preantral (PA) follicle development. METHODS: PA follicles isolated from lamb ovaries were cultured on PCL scaffold adopting a validated single-follicle protocol (Ctrl) or simulating a multiple-follicle condition by reproducing an artificial ovary engrafted with 5 or 10 PA (AO5PA and AO10PA). The incubations were protracted for 14 and 18 days before assessing scaffold-based microenvironment suitability to assist in vitro folliculogenesis (ivF) and oogenesis at morphological and functional level. RESULTS: The ivF outcomes demonstrated that PCL-scaffolds generate an appropriate biomimetic ovarian microenvironment supporting the transition of multiple PA follicles towards early antral (EA) stage by supporting follicle growth and steroidogenic activation. PCL-multiple bioengineering ivF (AO10PA) performed in long term generated, in addition, the greatest percentage of highly specialized gametes by enhancing meiotic competence, large chromatin remodeling and parthenogenetic developmental competence. CONCLUSIONS: The study showcased the proof of concept for a next-generation ART use of PCL-patterned scaffold aimed to generate transplantable artificial ovary engrafted with autologous early-stage follicles or to advance ivF technologies holding a 3D bioinspired matrix promoting a physiological long-term multiple PA follicle protocol.

Assessing the utility of the PC-PTSD-5 as a screening tool among a cancer survivor sample.

INTRODUCTION: Hematopoietic stem cell transplantation (HCT) is an intensive and invasive procedure used in cancer treatment that can lead to posttraumatic stress disorder (PTSD) symptoms. These symptoms are frequently overlooked in oncology and general health care settings. The suitability and utility of the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) within the cancer population remains uncertain. This study aims to evaluate its performance as a brief (five-item) case-finding screening alternative to the longer (20-item) PTSD Checklist for DSM-5 (PCL-5) in survivors who received an HCT 1 to 5 years ago. METHODS: A total of 817 cancer survivors completed the PC-PTSD-5 and PCL-5 during recruitment for a randomized clinical trial. Optimal cut scores for identifying probable PTSD and item performance were determined using indices correcting for chance and item response theory analyses. RESULTS: Of the HCT sample, 10.4% screened as positive for probable DSM-5 PTSD using the PCL-5. The PC-PTSD-5 exhibited strong internal consistency and significant associations with PCL-5 scores (total, r = .82; items, rs = .56-.61). A cutoff score of 2 provided optimal sensitivity for screening (κ[Se] = .95), whereas a cut score of 4 demonstrated the highest efficiency for detecting a probable DSM-5 PTSD diagnosis on the PCL-5 (κ[Eff] = .39). Item response theory analyses indicated that item 4 (numbing) of the PC-PTSD-5 yielded the most informative data, with other items potentially lacking incremental utility. CONCLUSION: Although not an instrument validation study, these findings offer efficient evidence for using the PC-PTSD-5 as a succinct screening tool among cancer survivors in a clinical context. TRIALS REGISTRATION: ClinicalTrials.gov, NCT04058795, registered 8/16/2019.

Subjective sleep parameters: A marker to PTSD symptoms evolution? A 4-year longitudinal study.

Disturbed sleep is a common feature after exposure to a traumatic event, especially when PTSD develops. However, although there is evidence suggesting a potential role of sleep disturbance in the progression of PTSD symptoms, the interrelationship between sleep and PTSD symptoms has yet to be determined. In order to address this knowledge gap, we have investigated the influence of initial sleep characteristics on the evolution of post-traumatic stress disorder (PTSD) symptoms over 4 years of follow-up among individuals exposed to the Brazilian Kiss nightclub fire. Participants were individuals exposed to the 2013 Kiss nightclub fire in Brazil. Sleep characteristics and PTSD symptoms were measured within the 4 years following the fire by self-report questionnaires, such as The Pittsburgh Sleep Quality Index (PSQI), and PTSD Checklist - Civilian version (PCL-C). Generalized estimating equations (GEE) models were used to examine the longitudinal associations (by estimating the relative effects of initial sleep problems on PTSD symptoms after adjusting for covariates). Comprehensive information concerning socio-demographic factors, health status, and sleep complaints were obtained. A total of 232 individuals were included. In GEE models, no significant interactions were observed between sociodemographic variables and PTSD symptoms in the follow-up period, however, associations were found between PTSD at baseline and the following factors: the female gender, the victim individuals and the existence of prior psychiatric disease. Initial subjective sleep parameters were strongly associated with PTSD symptoms over 4 years, mainly the presence of disturbed dreams (p = 0.012), increased sleep latency (p = 0.029), and reduced sleep duration (p = 0.012). Sleep complaints and PTSD symptoms were common among individuals after the disaster. The current study has found that the presence of sleep complaints, especially increased sleep latency, presence of disturbed dreams and short sleep duration, in the initial presentation after the fire was consistently associated with the perpetration of PTSD symptoms in the next 4 years of follow-up. These findings suggest that interventions addressing these sleep complaints have the potential to reduce the persistence and/or severity of PTSD symptoms.

Can cereal-based oral contrast agents-assisted ultrasound become an alternative to non-contrast magnetic resonance imaging (MRI) in radiological follow-up for pancreatic cystic lesions?

Background: Pancreatic cystic lesions (PCLs) are recommended to be examined by magnetic resonance imaging (MRI), yet MRI still has limitations, such as high costs, the risk of triggering claustrophobia, and relatively low availability compared with ultrasound. Oral contrast agents-assisted ultrasound has been used to examine the gallbladder and stomach, but whether oral contrast agents could improve the accuracy of transabdominal ultrasound (TAUS) for PCLs and could be a potential alternative to non-contrast MRI for PCL follow-up has not been studied. This study aimed to explore the value of cereal-based oral contrast agents in improving the accuracy of PCLs during TAUS. Methods: This is a prospective cohort study. Patients with PCL who were admitted to our center between January 2023 and January 2024 were enrolled, and TAUS was performed before and after taking cereal-based oral contrast agents. The imaging quality of the PCL was measured by structural visualization scores. The structural visualization scores of oral contrast agent-assisted ultrasound and non-contrast MRI were also compared. Results: A total of 27 patients with PCLs were enrolled, and 30 PCLs were detected. The sonolucency of the PCL improved after oral contrast agent administration. Before taking the agent, only 30% of patients had satisfactory sonolucency; after taking the oral contrast agent, the corresponding proportion reached 80% (P=0.002). The structural visualization score of the PCL determined by oral contrast agent-assisted TAUS was higher than that determined without the aid of an agent [1 (0-6) vs. 1 (0-3), P=0.001], which was mainly reflected in the increase in the number of visible septa after taking the agent. No significant difference was detected between the structural visualization score of the PCL examined by oral contrast agent-assisted TAUS and that examined by non-contrast MRI and the correlation between the 2 types of scores were satisfactory [1 (0-6) vs. 2 (0-7), P=0.070, Spearman correlation factor r=0.880]. Conclusions: This study used a structured scoring system to confirm that cereal-based oral contrast agents could improve the ultrasound quality of PCLs, and the correlation between the quality of oral contrast agent-assisted ultrasound and non-contrast MRI findings on PCLs was satisfactory. Further research to improve visualization of PCLs on TAUS using oral contrast agents could result in TAUS being a potential alternative to MRI in the follow-up of PCLs in resource-limited situations.

The Effects of Psychopathy Facets on Treatment Involvement.

The current study explored the relations between patient characteristics and psychopathic traits in predicting treatment involvement. We rated treatment involvement using detailed archival clinical files of 218 individuals committed to the Massachusetts Treatment Center (MTC). Psychopathy Checklist-Revised (PCL-R) scores had been rated from a previous study on the same sample. Overall, PCL-R Facets 2 and 4 significantly predicted decreases in treatment involvement, suggesting the characteristics associated with these facets have the most disruptive effects on treatment involvement. Exploratory analyses were also conducted assessing the relations between the PCL-R facets and the individual treatment involvement components. Whereas Facet 2 significantly predicted lower levels in all three individual treatment involvement components, Facet 4 only significantly predicted lower levels in two, highlighting the differentiating effects of these facets. Identifying the components that have either positive or negative effects on treatment involvement can allow clinicians to tailor treatments to optimize treatment involvement and outcome.

Graphene-enhanced PCL electrospun nanofiber scaffolds for cardiac tissue engineering.

Cardiovascular diseases, particularly myocardial infarction, have significant healthcare challenges due to the limited regenerative capacity of injured heart tissue. Cardiac tissue engineering (CTE) offers a promising approach to repairing myocardial damage using biomaterials that mimic the heart's extracellular matrix. This study investigates the potential of graphene nanopowder (Gnp)-enhanced polycaprolactone (PCL) scaffolds fabricated via electrospinning to improve the properties necessary for effective cardiac repair. This work aimed to analyze scaffolds with varying graphene concentrations (0.5%, 1%, 1.5%, and 2% by weight) to determine their morphological, chemical, mechanical, and biocompatibility characteristics. The results presented that incorporating graphene improves PCL scaffolds' mechanical properties and cellular interactions. The optimal concentration of 1% graphene significantly enhanced mechanical properties and biocompatibility, promoting cell adhesion and proliferation. These findings suggest that Gnp-enhanced PCL scaffolds at this concentration can serve as a potent substrate for CTE providing insights into designing more effective biomaterials for myocardial restoration.

Comparative morphology of the cruciate ligaments: A radiological study.

Background: The anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) are important structures to maintain knee stability. The present study aimed to further enrich understandings of the morphology of the cruciate ligaments and explore the relationship between the diameter of ACL and PCL. Method: This study collected valid MRI samples of 50 male and 50 female normal right knee joints and measured the diameter of each point of the ACL and PCL through the 3D Slicer. Results: The diameter of the ACL in the sagittal MRI of the normal right knee joint was significantly different from the diameter of each point of the PCL. The average diameter of each point of the ACL was larger than the diameter of the corresponding point of the PCL. Males and females had statistical differences in their PCL origin point, PCL midpoint, ACL origin point, ACL midpoint, and ACL insertion point diameters under sagittal MRI examination. The average diameter of males was greater than the average diameter of females at the above corresponding sites. In sagittal MRI scans of the normal right knee joint, we observed that only the origin point of the PCL exhibited a moderate correlation with the midpoint and insertion point of the ACL in terms of their respective diameters. Conclusion: The correlation between diameters of normal ACL and PCL in knee joint MRI was moderate and may help clinicians determine appropriate graft for cruciate ligament reconstruction surgery quickly for severe cruciate ligament injuries.

Enhanced differentiation of mesenchymal stem cells in coral-incorporated PCL/elastin scaffold enables 3D defect healing in osteoporosis rat model.

In osteoporosis, bone quality adversely affects the tissue structural competence which increases the risk of a complicated fracture healing. In the present study highly potent scaffold containing natural coral particles was designed and considered for the healing of critical size bone defect in osteoporosis rat model. Scaffold morphological evaluation confirmed the porous nanofibrous structure. Water uptake of about 900 % was obtained for the fabricated scaffold as the result of its composition and three-dimensional structure. Mechanical analysis revealed the compressive modulus of about 50 kPa for the fabricated coral-incorporated nanofibrous structure. In vitro cellular assessments revealed that the designed scaffold induces no toxicity and provides the proper substrate for cell attachment together with increased and prolonged cell proliferation. In vivo experiments demonstrated that implantation of the fabricated scaffold in the femoral defects of osteoporotic rats significantly increased the number of osteocytes and osteoblasts, and enhanced the BTV, and BMP-2 expression compared with the control group. Furthermore, it was observed that seeding the scaffolds with MSCs prior to implantation, resulted in substantial improvements in mRNA expression of the BMP-2 and VEGF genes and considerable enhancement in stereological findings such as significantly higher number of osteoblasts, osteocytes, TVB, and BTV.

3D-printed Mg-incorporated PCL-based scaffolds improves rotator cuff tendon-bone healing through regulating macrophage polarization.

Introduction: Rotator cuff tear (RCT) is a common shoulder injury impacting mobility and quality of life, while traditional surgeries often result in poor healing. Tissue engineering offers a promising solution, with poly (ε-caprolactone) (PCL) being favored due to its slow degradation, biocompatibility, and non-toxicity. However, PCL lacks sufficient compression resistance. Incorporating Mg, which promotes bone growth and has antibacterial effects, could enhance RCT repair. Methods: The Mg-incorporated PCL-based scaffolds were fabricated using a 3D printing technique. The scaffolds were incorporated with different percentages of Mg (0%, 5%, 10%, 15%, and 20%). The osteogenic activities and anti-inflammatory properties of the scaffolds were evaluated in vitro using human osteoblasts and macrophages. The tissue ingrowth and biocompatibility of the scaffolds were assessed in vivo using a rat model of RCT repair. The ability of the scaffolds to enhance macrophage polarization towards the M2 subtype and inhibit inflammation signaling activation was also investigated. Results: It was found that when incorporated with 10% Mg, PCL-based scaffolds exhibited the optimal bone repairing ability in vitro and in vivo. The in vitro experiments indicated that the successfully constructed 10 Mg/PCL scaffolds enhance osteogenic activities and anti-inflammatory properties. Besides, the in vivo studies demonstrated that 10 Mg/PCL scaffolds promoted tissue ingrowth and enhanced biocompatibility compared to the control PCL scaffolds. Furthermore, the 10 Mg/PCL scaffolds enhanced the macrophages' ability to polarize towards the M2 subtype and inhibited inflammation signaling activation. Discussion: These findings suggest that 3D-printed Mg-incorporated PCL scaffolds have the potential to improve RCT by enhancing osteogenesis, reducing inflammation, and promoting macrophage polarization. The incorporation of 10% Mg into PCL-based scaffolds provided the optimal combination of properties for RCT repair augmentation. This study highlights the potential of tissue engineering approaches in improving the outcomes of RCT repair and provides a foundation for future clinical applications.

Preparation of fibre-reinforced PLA-collagen@PLA-PCL@PCL-gelatin three-layer vascular graft by EDC/NHS cross-linking and its performance study.

In this study, a three-layer small diameter artificial vascular graft with a structure similar to that of natural blood vessels was first constructed by triple-step electrospinning technology, in which polylactic acid (PLA) and collagen (COL) were used for the inner layer, polylactic acid and polycaprolactone (PCL) was used for the middle layer and polycaprolactone and gelatin was used for the outer layer. The properties of the artificial vascular graft were adjusted by the EDC/NHS cross-linking agent through the reaction between the collagen or gelatine and EDC/NHS. The mechanical and hydrophilic properties of the cross-linked artificial vessels were substantially enhanced, with a maximum stress of 9.56 MPa in the axial direction and 9.31 MPa in the radial direction for the P/C (4:1) vascular graft, which exceeded that of many textile-based and natural vascular grafts. The increased hydrophilicity of the inner layer of the vessel before crosslinking was due to the addition of COL, and the inner layer of the artificial vessel after crosslinking had a substantial increase in hydrophilicity due to the production of a more hydrophilic urea derivative. The increased hydrophilicity led to easier cell adhesion to the inner layer of the artificial vessel, especially for the P/C (2:1) vascular graft, where the cell proliferation rate and adhesion were high due to COL incorporation and cross-linking. The three-layer vascular grafts studied did not lead to haemolysis. Therefore, the EDC/NHS cross-linked three-layer vascular graft had good mechanical properties, hydrophilicity, anticoagulation and could enhance cell adhesion and proliferation.

Current Status on Management of Primary Plasma Cell Leukemia.

PURPOSEOF REVIEW: Plasma Cell Leukemia (PCL) is a very rare and highly aggressive form of plasma cell dyscrasia. This review seeks to evaluate the outcomes of PCL in the context of combination novel agent therapy and stem cell transplant (SCT) protocols. RECENT FINDINGS: The diagnostic criteria for PCL have now evolved to include patients with 5% circulating PC. While management remains challenging, the incorporation of novel agent-based induction regimen has significantly improved early mortality and reduced attrition of patients proceeding to SCT. In recent prospective clinical trials, patients with PCL demonstrated an overall response rates of 69% to 86%, with progression-free and overall survival ranging from 13.8 to 15.5 months and 24.8 to 36.3 months, respectively. B-cell lymphoma 2 (BCL2) inhibitors, such as venetoclax present a targeted intervention opportunity for patients with PCL with t(11;14). Dedicated clinical trials tailored to PCL are crucial, integrating newer therapies in the frontline setting to further optimize responses and enhance overall outcomes.

Breast Tumor Cell Survival and Morphology in a Brain-like Extracellular Matrix Depends on Matrix Composition and Mechanical Properties.

Triple-negative breast cancer (TNBC) is the most invasive type of breast cancer with high risk of brain metastasis. To better understand interactions between breast tumors with the brain extracellular matrix (ECM), a 3D cell culture model is implemented using a thiolated hyaluronic acid (HA-SH) based hydrogel. The latter is used as HA represents a major component of brain ECM. Melt-electrowritten (MEW) scaffolds of box- and triangular-shaped polycaprolactone (PCL) micro-fibers for hydrogel reinforcement are utilized. Two different molecular weight HA-SH materials (230 and 420 kDa) are used with elastic moduli of 148 ± 34 Pa (soft) and 1274 ± 440 Pa (stiff). Both hydrogels demonstrate similar porosities. The different molecular weight of HA-SH, however, significantly changes mechanical properties, e.g., stiffness, nonlinearity, and hysteresis. The breast tumor cell line MDA-MB-231 forms mainly multicellular aggregates in both HA-SH hydrogels but sustains high viability (75%). Supplementation of HA-SH hydrogels with ECM components does not affect gene expression but improves cell viability and impacts cellular distribution and morphology. The presence of other brain cell types further support numerous cell-cell interactions with tumor cells. In summary, the present 3D cell culture model represents a novel tool establishing a disease cell culture model in a systematic way.

Enhanced Marine Biodegradation of Polycaprolactone through Incorporation of Mucus Bubble Powder from Violet Sea Snail as Protein Fillers.

Microplastics' spreading in the ocean is currently causing significant damage to organisms and ecosystems around the world. To address this oceanic issue, there is a current focus on marine degradable plastics. Polycaprolactone (PCL) is a marine degradable plastic that is attracting attention. To further improve the biodegradability of PCL, we selected a completely new protein that has not been used before as a functional filler to incorporate it into PCL, aiming to develop an environmentally friendly biocomposite material. This novel protein is derived from the mucus bubbles of the violet sea snail (VSS, Janthina globosa), which is a strong bio-derived material that is 100% degradable in the sea environment by microorganisms. Two types of PCL/bubble composites, PCL/b1 and PCL/b5, were prepared with mass ratios of PCL to bubble powder of 99:1 and 95:5, respectively. We investigated the thermal properties, mechanical properties, biodegradability, surface structure, and crystal structure of the developed PCL/bubble composites. The maximum biochemical oxygen demand (BOD) degradation for PCL/b5 reached 96%, 1.74 times that of pure PCL (≈55%), clearly indicating that the addition of protein fillers significantly enhanced the biodegradability of PCL. The surface morphology observation results through scanning electron microscopy (SEM) definitely confirmed the occurrence of degradation, and it was found that PCL/b5 underwent more significant degradation compared to pure PCL. The water contact angle measurement results exhibited that all sheets were hydrophobic (water contact angle > 90°) before the BOD test and showed the changes in surface structure after the BOD test due to the newly generated indentations on the surface, which led to an increase in surface toughness and, consequently, an increase in surface hydrophobility. A crystal structure analysis by wide-angle X-ray scattering (WAXS) discovered that the amorphous regions were decomposed first during the BOD test, and more amorphous regions were decomposed in PCL/b5 than in PCL, owing to the addition of the bubble protein fillers from the VSS. The differential scanning calorimeter (DSC) and thermal gravimetric analysis (TGA) results suggested that the addition of mucus bubble protein fillers had only a slight impact on the thermal properties of PCL. In terms of mechanical properties, compared to pure PCL, the mucus-bubble-filler-added composites PCL/b1 and PCL/b5 exhibited slightly decreased values. Although the biodegradability of PCL was significantly improved by adding the protein fillers from mucus bubbles of the VSS, enhancing the mechanical properties at the same time poses the next challenging issue.

Electrospun Ibuprofen-Loaded Blend PCL/PEO Fibers for Topical Drug Delivery Applications.

Electrospun drug-eluting fibers have demonstrated potentials in topical drug delivery applications, where drug releases can be modulated by polymer fiber compositions. In this study, blend fibers of polycaprolactone (PCL) and polyethylene oxide (PEO) at various compositions were electrospun from 10 wt% of polymer solutions to encapsulate a model drug of ibuprofen (IBP). The results showed that the average polymer solution viscosities determined the electrospinning parameters and the resulting average fiber diameters. Increasing PEO contents in the blend PCL/PEO fibers decreased the average elastic moduli, the average tensile strength, and the average fracture strains, where IBP exhibited a plasticizing effect in the blend PCL/PEO fibers. Increasing PEO contents in the blend PCL/PEO fibers promoted the surface wettability of the fibers. The in vitro release of IBP suggested a transition from a gradual release to a fast release when increasing PEO contents in the blend PCL/PEO fibers up to 120 min. The in vitro viability of blend PCL/PEO fibers using MTT assays showed that the fibers were compatible with MEF-3T3 fibroblasts. In conclusion, our results explained the scientific correlations between the solution properties and the physicomechanical properties of electrospun fibers. These blend PCL/PEO fibers, having the ability to modulate IBP release, are suitable for topical drug delivery applications.

Design and evaluation of mechanical strength of multi-material polymeric implants for mandibular reconstruction.

Reconstruction of mandible implants to address segmental abnormalities is still a challenging task, both in vitro and in vivo. The mechanical strength of the materials used is a critical factor that determines how well bone is regenerated. The reconstruction technique of mandibular abnormalities widely uses polymeric implants. It is critical to evaluate the mechanical resilience under different load cases, including axial, combined, and flexural loading conditions. This study developed implants for mandibular defects using a combination of four materials: polylactic acid (PLA), polyethylene terephthalate glycol (PETG), thermoplastic polyurethane (TPU), and polycaprolactone (PCL), with the aim of mimicking the inherent characteristics of cortical and cancellous bone structures and evaluating their mechanical properties to support bone Osseo integration. The eleven of these combinations of structures result below the micro strain threshold level of <3000 µÎµ, and the five combinations of the structures result in micro strain above the threshold value. The intact bone study results show that the stress under axial, combined, and flexural loading conditions is 27.6, 38.9, and 64.9 MPa, respectively. This study's stress results are lower than those from the intact bone study. The study found that the combinations of PLA and TPU material were most preferred for the cortical and cancellous bone regions of polymeric implants. These materials are also compatible with 3D printing. The results of this study can be used to find multi-material combinations that are strong and flexible.

Three-Dimensional Melted Electrowriting Drug Coating Fibers for the Prevention of Device-Associated Infections: A Pilot Study.

Medical device-related infections (DRIs), especially prevalent among critically ill patients, impose significant health and economic burdens and are mainly caused by bacteria. Severe infections often necessitate device removal when antibiotic therapy is inefficient, delaying recovery. To tackle this issue, PCL drug-eluting coated meshes were explored, and they were printed via melt electrowriting (MEW). These meshes were coated with gentamicin sulfate (GS) and tetracycline hydrochloride (TCH) and underwent FTIR analysis to confirm drug integration. Antimicrobial activity was assessed via agar diffusion assays and biofilm formation assays against bacterial strains: Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 43300, and Staphylococcus epidermidis ATCC 35984. FTIR analysis evidenced the presence of the drugs in the meshes. TCH displayed broad-spectrum antimicrobial activity against all strains, whereas GS was effective against all except S. aureus. These findings indicate the potential of cost-effective ultra-fine drug coating fibers for medical device applications, offering infection prevention during implantation. This preliminary study demonstrates the feasibility of producing drug-eluting fibers for DRI prevention through a non-toxic, fast, and cost-efficient technique, paving the way for enhanced patient care and reduced healthcare costs.

Energy-based devices and hyaluronic acid filler, polymer filler, and threads: Cadaveric study.

INTRODUCTION: The objective of this experiment was to investigate the thermal effects on hyaluronic acid fillers, PCL fillers, and PDO threads when exposed to controlled heat. This study aims to provide insights into how these materials respond to thermal energy, which is crucial for safe and effective cosmetic procedures involving combined modalities. MATERIALS AND METHODS: Cadaveric tissue was utilized to simulate clinical conditions. Hyaluronic acid fillers were injected at approximately 1 mm and 5 mm thicknesses, with variations in G' value (high and low). PCL fillers were similarly injected in 1 mm and 5 mm thicknesses. PDO threads were also inserted. All materials were injected at a depth of 2 cm. A thermometer was used to measure heat penetration, and a multi-wavelength laser was applied to the tissue. The temperature was maintained at 60°C for 5 min to assess whether heat penetrated more than 3 cm in thickness. Observations were made regarding the heat distribution and any physical changes in the fillers and threads. RESULTS: In thick layers, heat accumulated above the PCL filler without penetrating deeper layers. In thin layers, heat penetration was observed. For the HA fillers, heat energy was not blocked, regardless of the G' value or thickness. For the threads, no significant heat blockage effect was observed. For all materials, no visual changes were detected in any of the materials due to temperature exposure. DISCUSSION: The findings suggest that the thickness and composition of fillers significantly influence heat penetration. Thick PCL fillers act as a thermal barrier, whereas thin PCL fillers allow deeper heat penetration. Hyaluronic acid fillers do not impede heat transfer, regardless of their physical properties. PDO threads do not exhibit any notable thermal resistance. These insights are essential for optimizing the safety and efficacy of combined filler and energy-based device treatments in esthetic medicine.

3D-printed bone regeneration scaffolds modulate bone metabolic homeostasis through vascularization for osteoporotic bone defects.

The treatment of osteoporotic bone defects poses a challenge due to the degradation of the skeletal vascular system and the disruption of local bone metabolism within the osteoporotic microenvironment. However, it is feasible to modulate the disrupted local bone metabolism imbalance through enhanced vascularization, a theory termed "vascularization-bone metabolic balance". This study developed a 3D-printed polycaprolactone (PCL) scaffold modified with EPLQLKM and SVVYGLR peptides (PCL-SE). The EPLQLKM peptide attracts bone marrow-derived mesenchymal stem cells (BMSCs), while the SVVYGLR peptide enhances endothelial progenitor cells (EPCs) vascular differentiation, thus regulating bone metabolism and fostering bone regeneration through the paracrine effects of EPCs. Further mechanistic research demonstrated that PCL-SE promoted the vascularization of EPCs, activating the Notch signaling pathway in BMSCs, leading to the upregulation of osteogenesis-related genes and the downregulation of osteoclast-related genes, thereby restoring bone metabolic balance. Furthermore, PCL-SE facilitated the differentiation of EPCs into "H"-type vessels and the recruitment of BMSCs to synergistically enhance osteogenesis, resulting in the regeneration of normal microvessels and bone tissues in cases of femoral condylar bone defects in osteoporotic SD rats. This study suggests that PCL-SE supports in-situ vascularization, remodels bone metabolic translational balance, and offers a promising therapeutic regimen for osteoporotic bone defects.

A new application of avocado oil to enrich the biological activities of polycaprolactone membranes for tissue engineering.

The metabolites synthesized by plants to protect themselves serves as natural antimicrobial agents used in biomaterials. In this study, avocado oil (AO), was incorporated as a plant source and natural antimicrobial agent into polycaprolactone (PCL) membranes. The effects of varying AO ratios (25, 50, and 100 wt%.-PCL@25AO, PCL@50AO, PCL@100AO) on PCL membrane morphology, chemical structure, wettability, antimicrobial activity, and cell viabilities were investigated. It was demonstrated that the AO acts as a pore-forming agent in solvent-casted membranes. Young's modulus of the membranes varied between 602.68 and 31.92 MPa and more flexible membranes were obtained with increasing AO content. Inhibition zones of AO were recorded between 7.86 and 13.97 mm against clinically relevant microbial strains including bacteria, yeast, and fungi. Antimicrobial activity of AO was retained in PCL membranes at all ratios. Resazurin assay indicated that PCL@25AO membranes were cytocompatible with mouse fibroblast cells (L929 cell line) on day 6 showing 72.4% cell viability with respect to neat PCL membranes. Viability results were supported by scanning electron microscopy images and DAPI staining. The overall results of this study highlight the potential of PCL@25AO membranes as a biomaterial with antimicrobial properties, cytocompatibility, and mechanical strength suitable for various biomedical applications.

Tongxieyaofang Decotion Alleviates IBS by Modulating CHRM3 and Gut Barrier.

Purpose: Through network pharmacology combined with molecular docking and in vivo validation, the study examines the unexplored molecular mechanisms of Tongxieyaofang (TXYF) in the treatment of irritable bowel syndrome (IBS). In particular, the potential pharmacological mechanism of TXYF alleviating IBS by regulating CHRM3 and intestinal barrier has not been studied. Patients and Methods: LC-MS technique and TCMSP database were used in combination to identify the potential effective components and target sites of TXYF. Potential targets for IBS were obtained from Genecards and OMIM databases. PPI and cytoHub analysis for targets. Molecular docking was used to validate the binding energy of effective components with related targets and for visualization. GO and KEGG analysis were employed to identify target functions and signaling pathways. In the in vivo validation, wrap restraint stress-induced IBS model was employed to verify the change for cytoHub genes and CHRM3 expression. Furthermore, inflammatory changes of colon were observed by HE staining. The changes of Ach were verified by ELISA. IHC and WB validated CHRM3 and GNAQ/PLC/MLCK channel variations. AB-PAS test and WB test confirmed the protection of TXYF on gut barrier. The NF-κB/MLCK pathway was also verified. Results: In TXYF decoction, LC-MS identified 559 chemical components, with 23 remaining effective components after screening in TCMSP. KEGG analysis indicated that calcium plays a crucial role in TXYF treated for IBS. Molecular docking validated the binding capacity of the effective components Naringenin and Nobiletin with cytoHub-gene and CHRM3. In vivo validation demonstrated that TXYF inhibits the activation of Ach and CHRM3 in IBS, and inhibits for the GNAQ/PLC/MLCK axis. Additionally, TXYF downregulates TNF-α, MMP9, and NF-κB/MLCK, while modulating goblet cell secretion to protect gut barrier. Conclusion: TXYF inhibits Ach and CHRM3 expression, regulating the relaxation of intestinal smooth muscle via GNAQ/PLC/MLCK. Additionally, TXYF inhibits NF-κB/MLCK activated and goblet cell secretion to protect gut barrier.