Microvascular network based on the Hilbert curve for nutrient transport in thick tissue.

To address the uneven nutrient distribution within three-dimensional (3D) tissue models and organoids currently used in medical research, this study introduces a microvascular network based on the Hilbert curve. Our aim was to develop innovative solutions for enhancing nutrient supply in thick tissue models in vitro. By using 3D bioprinting, we engineered microvascular networks of varying Hilbert orders and validated their efficacy in enhancing nutrient uniformity through numerical simulations and experiments. These networks facilitated broader and more uniform nutrient distribution throughout the thick tissue models, particularly the 2° Hilbert microvascular structure, which occupies less space and significantly reduces regions of cellular death. Furthermore, we explored the potential of assembling larger tissue constructs using the 2° Hilbert microvascular network, showcasing its applicability in constructing large-scale biological models. The findings suggest that the 2° Hilbert microvascular structure is particularly effective in ensuring adequate nutrient delivery, thus enhancing the viability and functionality of large-volume tissue models. These innovations hold significant promise for advancing the fields of tissue engineering and regenerative medicine by improving nutrient delivery to in vitro thick tissue block models. This provides a robust foundation for future in vitro research and clinical applications, potentially leading to more effective treatments and interventions in the medical field. The development of these microvascular networks represents a crucial step forward in overcoming the limitations of current 3D tissue models and organoids, paving the way for more sophisticated and reliable biomedical research tools.

Finite element analysis and in vitro tests on endurance life and durability of composite bone substitutes.

Bone structures facilitate the regeneration and repair of bone tissue in regions where it has been damaged or destroyed, either temporarily or permanently. Therefore, the bone's fatigue strength and durability are crucial to its efficacy and longevity. Several variables, such as the construct's material qualities, design, and production procedure, loading and unloading cycles, and physiological conditions influence the endurance life of bone constructs. Metals, ceramics, and polymers are all routinely utilized to create bone substitutes, and each of these materials has unique features that might affect the fatigue strength and endurance life of the final product. The mechanical performance and capacity to promote bone tissue regeneration may be affected by the scaffold's design, porosity, and pore size. Researchers employ mechanical testing under cyclic loading circumstances as one example of an experimental approach used to assess bone construction endurance. These analyses can give us important information about the stress-strain behavior, resistance to multiple loading cycles, and fatigue strength of the new structure. Predicting the endurance life of the developed construct may also be possible with the use of simulations and numerical analyses. Hence, in order to create reliable and efficient constructs for bone tissue engineering, it is crucial to understand their fatigue strength and durability. The purpose of this study is to analyze the effective parameters for fatigue strength of bone structures and to gather the models and evaluations utilized in endurance life assessments.

Biofabrication & cryopreservation of tissue engineered constructs for on-demand applications.

Tissue engineered constructs prepared using conventional scaffold-based approaches have the potential to repair or regenerate damaged tissues and organs. Various scaffold fabrication strategies such as electrospinning, solvent casting, particulate leaching, gas foaming, hydrogels, freeze-drying, and 3D bioprinting have been used to fabricate artificial tissues. In recent times, 3D bioprinting has been predominantly used in various biomedical fields, including healthcare and pharmaceutical applications due to precision in 3D geometry. However, there are no viable strategies to preserve bioprinted constructs for on-demand applications because of the lack of specialized techniques or cryopreservation agents to maintain the cell viability and functionality of the bioprinted tissues. To solve this issue, cryopreservation of bioprinted tissues has emerged in recent years to develop methods to create and cryopreserve bioprinted constructs for on-demand applications. This review discusses various techniques used for producing ready-to-use tissue engineered products such as electrospinning, hydrogels, 3D bioprinting, and other bioprinting approaches. Further, the factors influencing the bioprinted tissues, such as cryoprotectants, polymer types and crosslinker concentrations, crosslinking approaches, viscoelastic properties, storage facilities, etc, were also discussed in detail. The potential of cryopreservable bioprinted tissues in various healthcare applications are elaborated with lucid examples. Finally, the conclusions and possible future directions for the fabrication and cryopreservation of tissue engineered products are highlighted.

The interplay of depressive symptoms and self-efficacy in adolescents: a network analysis approach.

Background: Self-efficacy, a critical psychological construct representing an individual's belief in their ability to control their motivation, behavior, and social environment. In adolescents, self-efficacy plays a crucial role in mental health, particularly concerning depressive symptoms. Despite substantial research, the complex interplay between self-efficacy and depressive symptoms in adolescents remains incompletely understood. Aims: The aim of this study is to investigate the complex interrelationships between self-efficacy and depressive symptoms in adolescents using psychological network analysis. Methods: The cross-sectional study involved 3,654 adolescents. Self-efficacy was assessed using the General Self-Efficacy Scale (GSES), and depressive symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9). Network analysis, incorporating the least absolute shrinkage and selection operator (LASSO) technique and centrality analysis, constructed and compared self-efficacy networks between depressive symptoms and healthy control groups. Results: Of the 3,654 participants, 560 (15.32%) met criteria for moderate to severe depressive symptoms (PHQ-9 scores ≥10). Among those with depressive symptoms, 373 (66.61%) had moderate, 126 (22.50%) had moderate-severe, and 61 (10.89%) had severe symptoms. Bivariate correlation analyses revealed a significant negative correlation between depressive symptoms and self-efficacy (r = -0.41, p < 0.001). The results of the network analysis showed significant differences in self-efficacy networks between adolescents with and without depressive symptoms (global strength: S = 0.25, p < 0.05). Depressed participants showed a network with reduced global strength, suggesting diminished interconnectedness among self-efficacy items. Specific connections within the self-efficacy network were altered in the presence of depressive symptoms. Bridge analysis revealed that effort-based problem-solving (bridge strengths = 0.13) and suicidal ideation (bridge strengths = 0.09) were the key bridge nodes. Conclusion: Adolescent depressive symptoms significantly impacts the self-efficacy network, resulting in diminished integration of self-efficacy and highlighting the complex interplay between self-efficacy and depressive symptoms. These findings challenge the traditional unidimensional view of self-efficacy and emphasize the need for tailored interventions focusing on unique self-efficacy profiles in adolescents with depressive symptoms.

3D-Printed Hydrogels with Engineered Nanocrystalline Domains as Functional Vascular Constructs.

Three-dimensionally printed (3DP) hydrogel-based vascular constructs have been investigated in response to the impaired function of blood vessels or organs by replicating exactly the 3D structural geometry to approach their function. However, they are still challenged by their intrinsic brittleness, which could not sustain the suture piercing and enable the long-term structural and functional stability during the direct contact with blood. Here, we reported the high-fidelity digital light processing (DLP) 3D printing of hydrogel-based vascular constructs from poly(vinyl alcohol)-based inks, followed by mechanical strengthening through engineering the nanocrystalline domains and subsequent surface modification. The as-prepared high-precision hydrogel vascular constructs were imparted with highly desirable mechanical robustness, suture tolerance, swelling resistance, antithrombosis, and long-term patency. Notably, the hydrogel-based bionic vein grafts, with precise valve structures, exhibited excellent control over the unidirectional flow and successfully fulfilled the biological functionalities and patency during a 4-week implantation within the deep veins of beagles, thus corroborating the promising potential for treating chronic venous insufficiency.

Development of Neural Cells and Spontaneous Neural Activities in Engineered Brain-Like Constructs for Transplantation.

Stem cell transplantation has demonstrated efficacy in treating neurological disorders by generating functional cells and secreting beneficial factors. However, challenges remain for current cell suspension injection therapy, including uncontrollable cell distribution, the potential for tumor formation, and limited ability to treat spatial defects. Therefore, implants with programmable cell development, tailored 3D structure, and functionalized biomaterials have the potential to both control cell distribution and reduce or heal spatial defects. Here, a biomimetic material system comprising gelatin, alginate, and fibrinogen has been developed for neural progenitor cell constructs using 3D printing. The resulting constructs exhibit excellent formability, stability, and developmental functions in vitro, as well as biocompatibility and integration into the hippocampus in vivo. The controllability, reproducibility, and material composition of the constructs show potential for use in personalized stem cell-based therapies for defective neurological disorders, neural development research, disease modeling, and organoid-derived intelligent systems.

A stakeholder-involved adaptation of pathways and resources for engagement and participation (PREP) material with young adults with complex disability in Australia: an implementation feasibility study.

PURPOSE: Pathways and Resources for Engagement and Participation (PREP) is an intervention to optimise individuals' participation by building problem-solving capacity and addressing environmental barriers. We investigated the feasibility of implementing PREP with young adults (18-30 years) with complex disability in Australia. MATERIALS AND METHODS: Explanatory sequential mixed methods study in three stages. (i) PREP materials were collaboratively adapted by the research team and consumer research partners. (ii) Steps 1 and 2 of PREP (YA Supplement) were completed with three young adults with disability, and preliminary feasibility explored using qualitative methods. (iii) The feasibility of implementing adapted materials was examined using quantitative and qualitative methods involving four young adults with disability, six support people and two service providers. RESULTS: Stage 1: PREP Young Adults Supplement (PREP (YA Supplement)) for use alongside PREP was developed. Stages 2 and 3: findings indicated PREP (YA Supplement) was acceptable, appropriate and feasible. Three themes were identified: setting and achieving goals were associated with challenges and benefits; finding the right time to implement the program was necessary; and PREP (YA Supplement) drives a shift to a participation-focused approach. CONCLUSION: PREP delivered alongside PREP (YA Supplement) appears feasible with Australian young adults with complex disability.

A novel supplement for the evidence-based Pathways and Resources for Engagement and Participation (PREP) intervention has been developed to enhance participation in life situations for young adults with disability in an Australian context (PREP Young Adult Supplement).Setting participation goals may be a substantial shift for young adults with disability and rehabilitation professionals, and involves considering attendance at, and involvement in, life situations.Implementation of PREP/PREP Young Adult Supplement is inherently flexible and can be adapted to suit the needs, preferences and circumstances of the participant.

The updated mouse universal genotyping array bioinformatic pipeline improves genetic QC in laboratory mice.

The MiniMUGA genotyping array is a popular tool for genetic quality control of laboratory mice and genotyping samples from most experimental crosses involving laboratory strains, particularly for reduced complexity crosses. The content of the production version of the MiniMUGA array is fixed; however, there is the opportunity to improve the array's performance and the associated report's usefulness by leveraging thousands of samples genotyped since the initial description of MiniMUGA. Here, we report our efforts to update and improve marker annotation, increase the number and the reliability of the consensus genotypes for classical inbred strains and substrains, and increase the number of constructs reliably detected with MiniMUGA. In addition, we have implemented key changes in the informatics pipeline to identify and quantify the contribution of specific genetic backgrounds to the makeup of a given sample, remove arbitrary thresholds, include the Y Chromosome and mitochondrial genome in the ideogram, and improve robust detection of the presence of commercially available substrains based on diagnostic alleles. Finally, we have updated the layout of the report to simplify the interpretation and completeness of the analysis and added a section summarizing the ideogram in table format. These changes will be of general interest to the mouse research community and will be instrumental in our goal of improving the rigor and reproducibility of mouse-based biomedical research.

Dendritic cells transfected with DNA constructs encoding CCR9, IL-10, and type II collagen demonstrate induction of immunological tolerance in an arthritis model.

Introduction: Restoring immune tolerance is a promising area of therapy for autoimmune diseases. One method that helps restore immunological tolerance is the approach using tolerogenic dendritic cells (tolDCs). In our study, we analyzed the effectiveness of using dendritic cells transfected with DNA constructs encoding IL-10, type II collagen, and CCR9 to induce immune tolerance in an experimental model of arthritis. Methods: Dendritic cell cultures were obtained from bone marrow cells of Balb/c mice. Dendritic cells (DCs) cultures were transfected with pmaxCCR9, pmaxIL-10, and pmaxCollagen type II by electroporation. The phenotype and functions of DCs were studied using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Migration of electroporated DCs was assessed in vitro. Induction of antigen-collagen induced arthritis (ACIA) was carried out according to the protocol in Balb/c mice. DCs were then administered to ACIA mice. The development of arthritis was monitored by measuring paw swelling with a caliper at different time points. The immunological changes were assessed by analyzing the content of antibodies to type II collagen using enzyme immunoassay. Additionally, a histological examination of the joint tissue was conducted, followed by data analysis. The results are as follows: DCs were obtained, characterized by reduced expression of CD80, CD86, and H-2Db (MHC class I), increased expression of CCR9, as well as producing IL-10 and having migratory activity to thymus cells. Transfected DCs induced T-regulatory cells (T-reg) and increased the intracellular content of IL-10 and TGF-ß in CD4+T cells in their co-culture, and also suppressed their proliferative activity in response to antigen. The administration of tolDCs transfected with DNA constructs encoding type II collagen, IL-10, and CCR9 to mice with ACIA demonstrated a reduction in paw swelling, a reduction in the level of antibodies to type II collagen, and a regression of histological changes. Conclusion: The study presents an approach by which DCs transfected with DNA constructs encoding epitopes of type II collagen, IL-10 and CCR9 promote the development of antigen-specific tolerance, control inflammation and reduce the severity of experimental arthritis through the studied mechanisms: induction of T-reg, IL-10, TGF-ß.

Sensitivity analysis and quality indicators for an in vitro oral irritation assay.

Biocompatibility testing using in vivo tests is often one of the final evaluations of new dental materials. To reduce the likelihood of failure at this late stage, predictive biocompatibility testing using in vitro methods is needed. In this study, we describe a sensitivity analysis of an oral irritation test by evaluating changes in the viability, using the MTT assay, of 3-D models with EpiOral constructs as a case study. Experiments that tested sources of variability in the assay led to recommendations regarding the storage of the constructs after arrival, pipetting procedure, use of MTT reagents from different vendors, use of transepithelial electrical resistance measurements, and statistical analyses. A statistical model was proposed to evaluate whether test substances yield a positive or negative result and the associated statistical confidence. Testing several test compounds such as the Y-4 polymer, that contains a known irritant, and dentally relevant substances such as sodium dodecyl sulfate (SDS) at varying concentrations revealed statistically significant results as expected. Lastly, a software app was designed to support a multiwell culture plate layout design. Overall, the findings and suggestions documented here will support the further development and potential standardization of this assay system and may be useful for the development of other assays using 3-D constructs.

New in vitro methods can support the development of novel dental materials by yielding information about their biocompatibility. In this study, an in vitro oral irritation assay was investigated to better understand what aspects of the method contribute to its variability. There is a potential that such a method could yield similar information to in vivo experiments and reduce animal testing.

Effects of pelvic fixation strategies and multi-rod constructs on biomechanics of the proximal junction in long thoracolumbar posterior instrumented fusions: a finite-element analysis.

PURPOSE: To assess the effect of various pelvic fixation techniques and number of rods on biomechanics of the proximal junction of long thoracolumbar posterior instrumented fusions. METHODS: A validated spinopelvic finite-element (FE) model was instrumented with L5-S1 ALIF and one of the following 9 posterior instrumentation configurations: (A) one traditional iliac screw bilaterally ("2 Iliac/2 Rods"); (B) T10 to S1 ("Sacral Only"); (C) unilateral traditional iliac screw ("1 Iliac/2 Rods"); (D) one traditional iliac screw bilaterally with one midline accessory rod ("2 Iliac/3 rods"); (E) S2AI screws connected directly to the midline rods ("2 S2AI/2 Rods"); and two traditional iliac screws bilaterally with two lateral accessory rods connected to the main rods at varying locations (F1: T10-11, F2: T11-12, F3: T12-L1, F4: L1-2) ("4 Iliac/4 Rods"). Range of motions (ROM) at T10-S1 and T9-T10 were recorded and compared between models. The T9-T10 intradiscal pressures and stresses of the T9-10 disc's annulus in addition to the von Mises stresses of the T9 and T10 vertebral bodies were recorded and compared. RESULTS: For T10-S1 ROM, 4 iliac/4 rods had lowest ROM in flexion and extension, while 2 S2AI/2 rods showed lowest ROM in rotation. Constructs with 3 or 4 rods had lower stresses on the primary rods compared to 2-rod constructs. At the proximal adjacent disc (T9-10), 4 iliac/4 rods showed lowest ROM, lowest intradiscal pressures, and lowest annular stress in all directions (most pronounced in flexion-extension). Under flexion and extension, 4 iliac/4 rods also showed the lowest von Mises stresses on the T10 vertebral body but the highest stresses on the T9 vertebral body. CONCLUSIONS: Dual iliac screws with 4 rods across the lumbosacral junction and extending to the thoracolumbar junction demonstrated the lowest T10-S1 ROM, the lowest adjacent segment disc (T9-T10) ROM, intradiscal pressures, and annular stresses, and the lowest UIV stresses, albeit with the highest UIV + 1 stresses. Additional studies are needed to confirm whether these biomechanical findings dictate clinical outcomes and effect rates of proximal junctional kyphosis and failure.

Recent Advances in Hydrogel-Based 3D Bioprinting and Its Potential Application in the Treatment of Congenital Heart Disease.

Congenital heart disease (CHD) is the most common birth defect, requiring invasive surgery often before a child's first birthday. Current materials used during CHD surgery lack the ability to grow, remodel, and regenerate. To solve those limitations, 3D bioprinting is an emerging tool with the capability to create tailored constructs based on patients' own imaging data with the ability to grow and remodel once implanted in children with CHD. It has the potential to integrate multiple bioinks with several cell types and biomolecules within 3D-bioprinted constructs that exhibit good structural fidelity, stability, and mechanical integrity. This review gives an overview of CHD and recent advancements in 3D bioprinting technologies with potential use in the treatment of CHD. Moreover, the selection of appropriate biomaterials based on their chemical, physical, and biological properties that are further manipulated to suit their application are also discussed. An introduction to bioink formulations composed of various biomaterials with emphasis on multiple cell types and biomolecules is briefly overviewed. Vasculogenesis and angiogenesis of prefabricated 3D-bioprinted structures and novel 4D printing technology are also summarized. Finally, we discuss several restrictions and our perspective on future directions in 3D bioprinting technologies in the treatment of CHD.

Collagen: The superior material for full-thickness oral mucosa tissue engineering.

BACKGROUND: Tissue engineering has significantly progressed in developing full-thickness oral mucosa constructs designed to replicate the natural oral mucosa. These constructs serve as valuable in vitro models for biocompatibility testing and oral disease modeling and hold clinical potential for replacing damaged or lost oral soft tissue. However, one of the major challenges in tissue engineering of the oral mucosa is the identification of an appropriate scaffold with optimal porosity, interconnected porous networks, biodegradability, and biocompatibility. These characteristics facilitate cell migration, nutrient delivery, and vascularization. Various biomaterials have been investigated for constructing tissue-engineered oral mucosa models; collagen has demonstrated superior outcomes compared with other materials. HIGHLIGHT: This review discusses the different types of tissue-engineered oral mucosa developed using various materials and includes articles published between January 2000 and December 2022 in PubMed and Google Scholar. The review focuses on the superiority of collagen-based scaffolds for tissue engineering of oral mucosa, explores in vitro applications, and discusses potential clinical applications. CONCLUSION: Among the various scaffold materials used for engineering the connective tissue of the oral mucosa, collagen-based scaffolds possess excellent biological properties, offering high-quality oral mucosa constructs and high resemblance to the native human oral mucosa in terms of histology and expression of various differentiation markers.

Multimaterial Printing of Serpentine Microarchitectures with Synergistic Mechanical/Piezoelectric Stimulation for Enhanced Cardiac-Specific Functional Regeneration.

Recreating the natural heart's mechanical and electrical environment is crucial for engineering functional cardiac tissue and repairing infarcted myocardium in vivo. In this study, multimaterial-printed serpentine microarchitectures are presented with synergistic mechanical/piezoelectric stimulation, incorporating polycaprolactone (PCL) microfibers for mechanical support, polyvinylidene fluoride (PVDF) microfibers for piezoelectric stimulation, and magnetic PCL/Fe3O4 for controlled deformation via an external magnet. Rat cardiomyocytes in piezoelectric constructs, subjected to dynamic mechanical stimulation, exhibit advanced maturation, featuring superior sarcomeric structures, improved calcium transients, and upregulated maturation genes compared to non-piezoelectric constructs. Furthermore, these engineered piezoelectric cardiac constructs demonstrate significant structural and functional repair of infarcted myocardium, as evidenced by enhanced ejection and shortening fraction, reduced fibrosis and inflammation, and increased angiogenesis. The findings underscore the therapeutic potential of piezoelectric cardiac constructs for myocardial infarction therapy.

mRNA Technology and Mucosal Immunization.

Current mRNA vaccines are mainly administered via intramuscular injection, which induces good systemic immunity but limited mucosal immunity. Achieving mucosal immunity through mRNA vaccination could diminish pathogen replication at the entry site and reduce interhuman transmission. However, delivering mRNA vaccines to mucosae faces challenges like mRNA degradation, poor entry into cells, and reactogenicity. Encapsulating mRNA in extracellular vesicles may protect the mRNA and reduce reactogenicity, making mucosal mRNA vaccines possible. Plant-derived extracellular vesicles from edible fruits have been investigated as mRNA carriers. Studies in animals show that mRNA vehiculated in orange-derived extracellular vesicles can elicit both systemic and mucosal immune responses when administered by the oral, nasal, or intramuscular routes. Once lyophilized, these products show remarkable stability. The optimization of mRNA to improve translation efficiency, immunogenicity, reactogenicity, and stability can be obtained through adjustments of the 5'cap region, poly-A tail, codons selection, and the use of nucleoside analogues. Recent studies have also proposed self-amplifying RNA vaccines containing an RNA polymerase as well as circular mRNA constructs. Data from parenterally primed animals demonstrate the efficacy of nasal immunization with non-adjuvanted protein, and studies in humans indicate that the combination of a parenteral vaccine with the natural exposure of mucosae to the same antigen provides protection and reduces transmission. Hence, mucosal mRNA vaccination would be beneficial at least in organisms pre-treated with parenteral vaccines. This practice could have wide applications for the treatment of infectious diseases.

Damage Resistance of Kevlar® Fabric, UHMWPE, PVB Multilayers Subjected to Concentrated Drop-Weight Impact.

The impact resistance of layered polymer structures using polyvinyl butyral (PVB) in combination with Kevlar® fabric and ultra-high molecular weight polyethylene (UHMWPE) were fabricated and tested. Methods of wet impregnation and hot-press impregnation and consolidation of fabric with PVB and UHMWPE were used to manufacture multilayer constructs. All sandwich constructs were fixed to the surface of ballistic clay and subject to a free drop-weight test with a conical impactor having a small contact area. All tests were made at the same impact energy of 9.3 J and velocity of 2.85 m/s. The change in the resistance force was recorded using a piezoelectric force sensor at the time intervals of 40 µs. Using experimental force-time history, the change in the impactor's velocity, the depth of impactor penetration, the energy transformation at various stages of impactor interaction with the sample, and other parameters were obtained. Three indicators were considered as the main criteria for the effectiveness of a sample's resistance to impact: (1) minimum deformation, bulging, of the panel backside at the moment of impact, (2) minimum absorption of impact energy per areal density, and (3) minimal or, better yet, no destruction of structural integrity. Under the tested conditions, the rigid Kevlar-PVB-Kevlar sandwich at the frontside and relatively soft but flexible UHMWPE-Kevlar-UHMWPE layers in the middle helped to localize and absorb impact energy, while the backside Kevlar-PVB-Kevlar sandwich minimized local bulging providing the best overall performance. The front layer damage area was very shallow and less than two impactor tip diameters. The backside bulging was also less than in any other tested configurations.

Chinese hamster ovary cell line engineering strategies for modular production of custom extracellular vesicles.

Continuously secreted by all cell types, extracellular vesicles (EVs) are small membrane-bound structures which shuttle bioactive cargo between cells across their external environment. Their central role as natural molecular messengers and ability to cross biological barriers has garnered significant attention in the use of EVs as therapeutic delivery vehicles. Still, harnessing the potential of EVs is faced with many obstacles. A cell line engineering approach can be used to exploit EVs to encapsulate a bespoke cargo of interest. However, full details regarding native EV-loading mechanisms remain under debate, making this a challenge. While Chinese hamster ovary (CHO) cells are well known to be the preferred host for recombinant therapeutic protein production, their application as an EV producer cell host has been largely overlooked. In this study, we engineered CHO DG44 cells to produce custom EVs with bespoke cargo. To this end, genetic constructs employing split green fluorescent protein technology were designed for tagging both CD81 and protein cargoes to enable EV loading via self-assembling activity. To demonstrate this, NanoLuc and mCherry were used as model reporter cargoes to validate engineered loading into EVs. Experimental findings indicated that our custom EV approach produced vesicles with up to 15-fold greater cargo compared with commonly used passive loading strategies. When applied to recipient cells, we observed a dose-dependent increase in cargo activity, suggesting successful delivery of engineered cargo via our custom CHO EVs.

Topping-Off a Long Thoracic Stabilization With Semi-Rigid Constructs May Have Favorable Biomechanical Effects to Prevent Proximal Junctional Kyphosis: A Biomechanical Comparison.

STUDY DESIGN: In-vitro cadaveric biomechanical study. OBJECTIVES: Long posterior spinal fusion is a standard treatment for adult spinal deformity. However, these rigid constructs are known to alter motion and stress to the adjacent non-instrumented vertebrae, increasing the risk of proximal junctional kyphosis (PJK). This study aimed to biomechanically compare a standard rigid construct vs constructs "topped off" with a semi-rigid construct. By understanding semi-rigid constructs' effect on motion and overall construct stiffness, surgeons and researchers could better optimize fusion constructs to potentially decrease the risk of PJK and the need for revision surgery. METHODS: Nine human cadaveric spines (T1-T12) underwent non-destructive biomechanical range of motion tests in pure bending or torsion and were instrumented with an all-pedicle-screw (APS) construct from T6-T9. The specimens were sequentially instrumented with semi-rigid constructs at T5: (i) APS plus sublaminar bands; (ii) APS plus supralaminar hooks; (iii) APS plus transverse process hooks; and (iv) APS plus short pedicle screws. RESULTS: APS plus transverse process hooks had a range of motion (ie, relative angle) for T4-T5 and T5-T6, as well as an overall mechanical stiffness for T1-T12, that was more favourable, as it reduced motion at adjacent levels without a stark increase in stiffness. Moreover, APS plus transverse process hooks had the most linear change for range of motion across the entire T3-T7 range. CONCLUSIONS: Present findings suggest that APS plus transverse process hooks has a favourable biomechanical effect that may reduce PJK for long spinal fusions compared to the other constructs examined.

Social cognition correlates of self-management behaviors in patients with familial hypercholesterolemia (FH): A meta-analytic review.

OBJECTIVE: Familial Hypercholesterolemia (FH) is an inherited disorder leading to increased risk of premature atherosclerotic cardiovascular disease. This risk can be ameliorated through adherence to pharmacological treatment and salient lifestyle behaviors (e.g., physical activity participation, healthy eating). Identifying theory-based, modifiable determinants of these behaviors may inform behavioral interventions promoting participation in FH self-management behaviors. We aimed to identify the belief-based social cognition constructs uniquely associated with intentions to perform, and actual participation in, FH self-management behaviors in the extant research. METHOD: A systematic database search identified studies (k = 9, N = 1394) reporting relations between social cognition theory constructs and intention toward, or actual participation in, self-management behaviors in FH patients. As no studies examining prospectively-measured behaviors were identified, we tested relations among social cognition constructs, intentions, and past FH-self-management behavior using random effects multi-level meta-analysis and meta-analytic structural equation modelling. RESULTS: We found non-zero averaged correlations among the key social cognition constructs (attitudes, norms, risk perceptions, self-efficacy), intentions, and past behavior. A meta-analytic structural equation model indicated non-zero averaged direct effects of attitudes, norms, self-efficacy, and past behavior on FH self-management behavioral intentions. There were also non-zero averaged indirect effects of past behavior on intentions mediated by the social cognition constructs. CONCLUSION: Findings provide evidence to support the proposed model and highlight the importance of personal, normative, and capacity related beliefs and past experience as unique correlates of intentions to perform FH self-management behaviors. The model may signal potential constructs that could be targeted in behavioral interventions to promote participation in FH self-management behaviors.

Nanostructured Biopolymer-Based Constructs for Cartilage Regeneration: Fabrication Techniques and Perspectives.

The essential functions of cartilage, such as shock absorption and resilience, are hindered by its limited regenerative capacity. Although current therapies alleviate symptoms, novel strategies for cartilage regeneration are desperately needed. Recent developments in three-dimensional (3D) constructs aim to address this challenge by mimicking the intrinsic characteristics of native cartilage using biocompatible materials, with a significant emphasis on both functionality and stability. Through fabrication methods such as 3D printing and electrospinning, researchers are making progress in cartilage regeneration; nevertheless, it is still very difficult to translate these advances into clinical practice. The review emphasizes the importance of integrating various fabrication techniques to create stable 3D constructs. Meticulous design and material selection are required to achieve seamless cartilage integration and durability. The review outlines the need to address these challenges and focuses on the latest developments in the production of hybrid 3D constructs based on biodegradable and biocompatible polymers. Furthermore, the review acknowledges the limitations of current research and provides perspectives on potential avenues for effectively regenerating cartilage defects in the future.