Patient-Specific 3-Dimensional Model of Smooth Muscle Cell and Extracellular Matrix Dysfunction for the Study of Aortic Aneurysms.

INTRODUCTION: Abdominal aortic aneurysms (AAAs) are associated with overall high mortality in case of rupture. Since the pathophysiology is unclear, no adequate pharmacological therapy exists. Smooth muscle cells (SMCs) dysfunction and extracellular matrix (ECM) degradation have been proposed as underlying causes. We investigated SMC spatial organization and SMC-ECM interactions in our novel 3-dimensional (3D) vascular model. We validated our model for future use by comparing it to existing 2-dimensional (2D) cell culture. Our model can be used for translational studies of SMC and their role in AAA pathophysiology. MATERIALS AND METHODS: SMC isolated from the medial layer of were the aortic wall of controls and AAA patients seeded on electrospun poly-lactide-co-glycolide scaffolds and cultured for 5 weeks, after which endothelial cells (EC) are added. Cell morphology, orientation, mechanical properties and ECM production were quantified for validation and comparison between controls and patients. RESULTS: We show that cultured SMC proliferate into multiple layers after 5 weeks in culture and produce ECM proteins, mimicking their behavior in the medial aortic layer. EC attach to multilayered SMC, mimicking layer interactions. The novel SMC model exhibits viscoelastic properties comparable to biological vessels; cytoskeletal organization increases during the 5 weeks in culture; increased cytoskeletal alignment and decreased ECM production indicate different organization of AAA patients' cells compared with control. CONCLUSION: We present a valuable preclinical model of AAA constructed with patient specific cells with applications in both translational research and therapeutic developments. We observed SMC spatial reorganization in a time course of 5 weeks in our robust, patient-specific model of SMC-EC organization and ECM production.

An in vitro model to evaluate the properties of matrices produced by fibroblasts from osteogenesis imperfecta and Ehlers-Danlos Syndrome patients.

AIM OF THE STUDY: Osteogenesis imperfecta and Ehlers Danlos syndrome are hereditary disorders caused primarily by defective collagen regulation. Osteogenesis imperfecta patients were divided to haploinsufficient and dominant negative depending on the effect of COL1A1 and COL1A2 mutations whereas Ehlers Danlos syndrome patients had a mutation in PLOD1. Although collagen abnormalities have been extensively studied in monolayer cultures, there are no reports about 3D in vitro models which may reflect more accurately the dynamic cell environment. This is the first study presenting the structural and mechanical characterization of a 3D cell-secreted model using primary patient fibroblasts. MATERIALS AND METHODS: Fibroblasts from patients with osteogenesis imperfecta and Ehlers Danlos syndrome were cultured with ascorbic acid for 5 weeks. The effect of mutations on cytosolic and secreted collagen was tested by electrophoresis following incubation with radiolabeled 14C proline. Extracellular matrix was studied in terms of collagen fiber orientation, stiffness, as well as glycosaminoglycan and collagen content. RESULTS AND CONCLUSIONS: Osteogenesis imperfecta patients with haploinsufficient mutations had higher percentage of anisotropic collagen fibers alignment compared to other patient groups; all patients had a lower percentage of anisotropic samples compared to healthy controls. This correlated with higher average stiffness in the control group. Glycosaminoglycan content was lower in the control and haploinsufficient groups. In cells with PLOD1 mutations, there were no differences in PLOD2 expression. This proof of concept study was able to show differences in collagen fiber orientation between different patient groups which can potentially pave the way towards the development of 3D models aiming at improved investigation of disease mechanisms.

Morphogenesis of aligned collagen fibers in the annulus fibrosus: Mammals versus avians.

The mammalian intervertebral disc (IVD) consists of a gel-like, disordered nucleus pulposus (NP) surrounded by a highly ordered collagen structure, the annulus fibrosus (AF). While this concentric array of lamellae has been amply studied, its physical origin is poorly understood. The notochord is a rod-like organ located in the mid-line of the growing embryo and plays an essential role in IVD development. The aim of this study was to elucidate the effect of notochord development on the collagen fiber arrangement evolution in the AF. To that end, we studied IVD development in mouse embryos and compared these observations to those from chicken embryos, which do not form the typical laminar structure around the NP. In mouse, cross-aligned collagen arrangement of the AF forms from the sclerotome upon bulging of the notochord to become NP. By contrast, the notochord in the chicken embryo swells substantially without the physical restrictions of the future vertebrae and thus do not bulge. From these observations, we conclude that physical and geometrical constrictions are essential for the formation of the highly structured AF.

Collagen Matrix Remodeling in Stented Pulmonary Arteries after Transapical Heart Valve Replacement.

The use of valved stents for minimally invasive replacement of semilunar heart valves is expected to change the extracellular matrix and mechanical function of the native artery and may thus impair long-term functionality of the implant. Here we investigate the impact of the stent on matrix remodeling of the pulmonary artery in a sheep model, focusing on matrix composition and collagen (re)orientation of the host tissue. Ovine native pulmonary arteries were harvested 8 (n = 2), 16 (n = 4) and 24 (n = 2) weeks after transapical implantation of self-expandable stented heart valves. Second harmonic generation (SHG) microscopy was used to assess the collagen (re)orientation of fresh tissue samples. The collagen and elastin content was quantified using biochemical assays. SHG microscopy revealed regional differences in collagen organization in all explants. In the adventitial layer of the arterial wall far distal to the stent (considered as the control tissue), we observed wavy collagen fibers oriented in the circumferential direction. These circumferential fibers were more straightened in the adventitial layer located behind the stent. On the luminal side of the wall behind the stent, collagen fibers were aligned along the stent struts and randomly oriented between the struts. Immediately distal to the stent, however, fibers on both the luminal and the adventitial side of the wall were oriented in the axial direction, demonstrating the stent impact on the collagen structure of surrounding arterial tissues. Collagen orientation patterns did not change with implantation time, and biochemical analyses showed no changes in the trend of collagen and elastin content with implantation time or location of the vascular wall. We hypothesize that the collagen fibers on the adventitial side of the arterial wall and behind the stent straighten in response to the arterial stretch caused by oversizing of the stent. However, the collagen organization on the luminal side suggests that stent-induced remodeling is dominated by contact guidance.

3D printed pH-responsive tablets containing N-acetylglucosamine-loaded methylcellulose hydrogel for colon drug delivery applications.

The pH-responsive drug release approach in combination with three-dimensional (3D) printing for colon-specific oral drug administration can address the limitations of current treatments such as orally administered solid tablets. Such existing treatments fail to effectively deliver the right drug dosage to the colon. In order to achieve targeted drug release profiles, this work aimed at designing and producing 3D printed tablet shells using Eudragit® FS100 and polylactic acid (PLA) where the core was filled with 100 µl of N-acetylglucosamine (GlcNAc)-loaded methyl cellulose (MC) hydrogel. To meet the requirements of such tablets, the effects of polymer blending ratios and MC concentrations on physical, thermal, and material properties of various components of the tablets and most importantly in vitro drug release kinetics were investigated. The tablets with 80/20 wt% of Eudragit® FS100/PLA and the drug-loaded hydrogel with 30 mg/ml GlcNAc and 3% w/v MC showed the most promising results having the best printability, processability, and drug release kinetics besides being non-cytotoxic. Manufacturing of these tablets will be the first milestone in shifting from the conventional "one size fits all" approach to personalized medicine where different dosages and various combinations of drugs can be effectively delivered to the inflammation site.

Thermoresponsive nanofibers loaded with antimicrobial α-aminophosphonate-o/w emulsion supported by cellulose nanocrystals for smart wound care patches.

Long-term topical application of antibiotics on wounds has led to the emergence of drug-resistant bacterial infections. Antibiotic incorporation into the wound dressing requires enormous advancement of the field to ensure that the needed dose is released when the infection arises. This study synthesized a series of antimicrobial α-aminophosphonate derivatives, and the most effective compound was incorporated into thermoresponsive wound dressing patches. Wound dressing mats were fabricated by needleless electrospinning, and the resultant nanofiber mats were coated with a thermoresponsive eicosane/cellulose nanocrystals o/w system loaded with active α-aminophosphonate derivatives. Chemical, physical, thermal, and antimicrobial properties of the wound dressings were characterized wound dressings. Using SEM analysis, Nanofibers spun with 20 % w/v solutions were selected for drug-emulsion loading since they showed lower diameters with higher surface area. Furthermore, the drug-emulsion coating on the electrospun dressings improved the hydrophilicity of the wound dressings, and the thermoresponsive behavior of the mats was proved using differential scanning calorimetry data. Finally, the drug-loaded electrospun meshes were found active against tested microorganisms, and clear inhibition zones were observed. In conclusion, this novel approach of synthesizing a new family of antimicrobial molecules and their incorporation into nanofibers from renewable sources exhibits great potential for smart and innovative dressings.

Mechanical characterization of a novel biomimetic artificial disc for the cervical spine.

A novel biomimetic artificial intervertebral disc (bioAID) replacement implant has been developed containing a swelling hydrogel representing the nucleus pulposus, a tensile strong fiber jacket as annulus fibrosus and titanium endplates with pins to primarily secure the device between the vertebral bodies. In this study, the design safety of this novel implant was evaluated based on several biomechanical parameters, namely compressive strength, shear-compressive strength, risk of subsidence and device expulsion as well as identifying the diurnal creep-recovery characteristics of the device. The bioAID remained intact up to 1 kN under static axial compression and only 0.4 mm of translation was observed under a compressive shear load of 20 N. No subsidence was observed after 0.5 million cycles of sinusoidal compressive loading between 50 and 225 N. After applying 400 N in antero-posterior direction under 100 N axial compressive preload, approximately 2 mm displacement was found, being within the range of displacements reported for other commercially available cervical disc replacement devices. The diurnal creep recovery behavior of the bioAID closely resembled what has been reported for natural intervertebral discs in literature. Overall, these results indicate that the current design can withstand (shear-compression loads and is able to remain fixed in a mechanical design resembling the vertebral bodies. Moreover, it is one of the first implants that can closely mimic the poroelastic and viscoelastic behavior of natural disc under a diurnal loading pattern.

Self-crosslinked polyvinyl alcohol/cellulose nanofibril cryogels loaded with synthesized aminophosphonates as antimicrobial wound dressings.

Microbial infection is the most common obstacle in the wound healing process, leading to wound healing impairment and complications and ultimately increasing morbidity and mortality. Due to the rising number of pathogens evolving resistance to the existing antibiotics used for wound care, alternative approaches are urgently required. In this study, α-aminophosphonate derivatives as antimicrobial agents were synthesized and incorporated into self-crosslinked tri-component cryogels composed of fully hydrolyzed polyvinyl alcohol (PVA-F), partially hydrolyzed polyvinyl alcohol (PVA-P), and cellulose nanofibrils (CNFs). Initially, the antimicrobial activity of four α-aminophosphonate derivatives against selected skin bacterial species was tested and their minimum inhibitory concentration was determined based on which the most effective compound was loaded into the cryogels. Next, the physical and mechanical properties of cryogels with various blending ratios of PVA-P/PVA-F and fixed amounts of CNFs were assessed, and drug release profiles and biological activities of drug-loaded cryogels were analyzed. Assessment of α-aminophosphonate derivatives showed the highest efficacy of a cinnamaldehyde-based derivative (Cinnam) against both Gram-negative and Gram-positive bacteria compared to other derivatives. The physical and mechanical properties of cryogels showed that PVA-P/PVA-F with a 50/50 blending ratio had the highest swelling ratio (1600%), surface area (523 m2 g-1), and compression recoverability (72%) compared to that with other blending ratios. Finally, antimicrobial and biofilm development studies showed that the cryogel loaded with a Cinnam amount of 2 mg (relative to polymer weight) showed the most sustained drug release profile over 75 h and had the highest efficacy against Gram-negative and Gram-positive bacteria. In conclusion, self-crosslinked tri-component cryogels loaded with the synthesized α-aminophosphonate derivative, having both antimicrobial and anti-biofilm formation properties, can have a significant impact on the management of uprising wound infection.

Biomechanical evaluation of a novel biomimetic artificial intervertebral disc in canine cervical cadaveric spines.

Background Context: Cervical disc replacement (CDR) aims to restore motion of the treated level to reduce the risk of adjacent segment disease (ASD) compared with spinal fusion. However, first-generation articulating devices are unable to mimic the complex deformation kinematics of a natural disc. Thus, a biomimetic artificial intervertebral CDR (bioAID), containing a hydroxyethylmethacrylate (HEMA)-sodium methacrylate (NaMA) hydrogel core representing the nucleus pulposus, an ultra-high-molecular-weight-polyethylene fiber jacket as annulus fibrosus, and titanium endplates with pins for primary mechanical fixation, was developed. Purpose: To assess the initial biomechanical effect of the bioAID on the kinematic behavior of the canine spine, an ex vivo biomechanical study in 6-degrees-of-freedom was performed. Study Design: A canine cadaveric biomechanical study. Methods: Six cadaveric canine specimens (C3-C6) were tested in flexion-extension (FE), lateral bending (LB) axial rotation (AR) using a spine tester in three conditions: intact, after C4-C5 disc replacement with bioAID, and after C4-C5 interbody fusion. A hybrid protocol was used where first the intact spines were subjected to a pure moment of ±1 Nm, whereafter the treated spines were subjected to the full range of motion (ROM) of the intact condition. 3D segmental motions at all levels were measured while recording the reaction torsion. Biomechanical parameters studied included ROM, neutral zone (NZ), and intradiscal pressure (IDP) at the adjacent cranial level (C3-C4). Results: The bioAID retained the sigmoid shape of the moment-rotation curves with a NZ similar to the intact condition in LB and FE. Additionally, the normalized ROMs at the bioAID-treated level were statistically equivalent to intact during FE and AR while slightly decreased in LB. At the two adjacent levels, ROMs showed similar values for the intact compared to the bioAID for FE and AR and an increase in LB. In contrast, levels adjacent to the fused segment showed an increased motion in FE and LB as compensation for the loss of motion at the treated level. The IDP at the adjacent C3-C4 level after implantation of bioAID was close to intact values. After fusion, increased IDP was found compared with intact but did not reach statistical significance. Conclusion: This study indicates that the bioAID can mimic the kinematic behavior of the replaced intervertebral disc and preserves that for the adjacent levels better than fusion. As a result, CDR using the novel bioAID is a promising alternative treatment for replacing severely degenerated intervertebral discs.

Nanofibrous Hydrogel Nanocomposite Based on Strontium-Doped Bioglass Nanofibers for Bone Tissue Engineering Applications.

The main aim of the current study is to fabricate an osteocompatible, bioactive, porous, and degradable bone tissue engineering scaffold. For this purpose, bioactive glasses (BGs) were chosen due to their similarity to bone's natural mineral composition, and the effect of replacing Ca ions with Sr on their properties were considered. First, strontium-containing BGs (Sr-BGs) were synthesized using the electrospinning technique and assembled by the sol-gel method, then they were incorporated into the alginate (Alg) matrix. Photographs of the scanning electron microscope (SEM) showed that the BG nanofibers have a diameter of 220 ± 36 nm, which was smaller than the precursor nanofibers (275 ± 66 nm). The scaffolds possess a porous internal microstructure (230-330 nm pore size) with interconnected pores. We demonstrated that the scaffolds could be degraded in the acetate sodium buffer and phosphate-buffered saline. The osteoactivity of the scaffolds was confirmed via visual inspection of the SEM illustrations after seven days of immersing them in the SBF solution. In vitro assessments disclosed that the produced Alg-based composites including Sr-BGs (Alg/Sr-BGs) are blood-compatible and biocompatible. Accumulating evidence shows that Alg/Sr-BG (5%, 10%, and 15%) hydrogels could be a promising scaffold for bone regeneration.

Bioactive tri-component nanofibers from cellulose acetate/lignin//N-vanillidene-phenylthiazole copper-(II) complex for potential diaper dermatitis control.

Current research targets innovative medical textiles of nanofibrous nature and antibacterial activity to prevent diaper dermatitis. The work is based on electrospun nanofibers from cellulose acetate (CA) and lignin (Lig) polymers. A series of new copper complexes were synthesized and loaded to the CA/Lig solution mix then subjected to electrospinning, giving rise to the tricomponent bioactive mats CA/Lig/Cu-complex. The surface morphology of electrospun nanofiber mats was smooth and homogenous as the concentration of lignin increased in the mixture. The incorporation of lignin improved the electrospinnability of the cellulose acetate; however, it increased the fiber diameter. The water contact angle, absorption underload were significantly improved as lignin content increased. The incorporation of Cu-complex in electrospun CA and CA/Lig fiber mats occurred without any substantial change in the surface morphology, indicating well encapsulation of the complex. The electrospun mats were active against Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus epidermidis, and Streptococcus faecalis. The cytotoxicity, protein leakage, and biological results, together with the above studies, would advocate copper complex loaded CA/Lig nanofibers as a potential candidate for hygienic applications.

Supercritical CO2 sterilization: An effective treatment to reprocess FFP3 face masks and to reduce waste during COVID-19 pandemic.

The outbreak of COVID-19 pandemic unveiled an unprecedented scarcity of personal protective equipment (PPE) available in sanitary premises and for the population worldwide. This situation fostered the development of new strategies to reuse PPE that would ensure sterility and, simultaneously, preserve the filtering properties of the materials. In addition, the reuse of PPEs by reprocessing could reduce the environmental impact of the massive single-use and disposal of these materials. Conventional sterilization techniques such as steam or dry heat, ethylene oxide, and gamma irradiation may alter the functional properties of the PPEs and/or leave toxic residues. Supercritical CO2 (scCO2)-based sterilization is herein proposed as a safe, sustainable, and rapid sterilization method for contaminated face masks while preserving their performance. The functional (bacterial filtration efficiency, breathability, splash resistance, straps elasticity) properties of the processed FFP3 face masks were evaluated after 1 and 10 cycles of sterilization. Log-6 sterilization reduction levels were obtained for face masks contaminated with Bacillus pumilus endospores at mild operating conditions (CO2 at 39 °C and 100 bar for 30 min) and with low contents of H2O2 (150 ppm). Physicochemical properties of the FFP3 face masks remained unchanged after reprocessing and differences in efficacy were not observed neither in the filtration tests, following UNE-EN 14683, nor in the integrity of FFP3 filtration after the sterilization process. The herein presented method based on scCO2 technology is the first reported protocol achieving the reprocessing of FFP3 masks up to 10 cycles while preserving their functional properties.

Drug-Eluting Medical Textiles: From Fiber Production and Textile Fabrication to Drug Loading and Delivery.

Drug-eluting medical textiles have recently gained great attention to be used in different applications due to their cost effectiveness and unique physical and chemical properties. Using various fiber production and textile fabrication technologies, fibrous constructs with the required properties for the target drug delivery systems can be designed and fabricated. This review summarizes the current advances in the fabrication of drug-eluting medical textiles. Different fiber production methods such as melt-, wet-, and electro-spinning, and textile fabrication techniques such as knitting and weaving are explained. Moreover, various loading processes of bioactive agents to obtain drug-loaded fibrous structures with required physicochemical and morphological properties, drug delivery mechanisms, and drug release kinetics are discussed. Finally, the current applications of drug-eluting fibrous systems in wound care, tissue engineering, and transdermal drug delivery are highlighted.

Cellulose aerogel micro fibers for drug delivery applications.

Textile engineering can offer a multi-scale toolbox via various fiber or textile fabrication methods to obtain woven or nonwoven aerogels with different structural and mechanical properties to overcome the current limitations of polysaccharide-based aerogels, such as poor mechanical properties and undeveloped shaping techniques. Hereby, a high viscous solution of microcrystalline cellulose and zinc chloride hydrate was wet spun to produce mono and multi-filament alcogel microfibers. Subsequently, cellulose aerogel fibers (CAF) were produced and impregnated with model drugs using supercritical CO2 processes. Fibers were characterized in terms of morphology and textural properties, thermal stability, mechanical properties, and in vitro biological and drug release assessments. Loaded and non-loaded CAFs proved to have a macro-porous outer shell and a nano-porous inner core with interconnected pore structure and a specific area in the range of 100-180 m2/g. The CAFs with larger diameter (d ~ 235 µm) were able to form knitted mesh while lower diameter fibers (d ~ 70 µm) formed needle punched nonwoven textiles. Humidity and water uptake assessments indicated that the fibrous structures were highly moisture absorbable and non-toxic with immediate drug release profiles due to the highly open interconnected porous structure of the fibers. Finally, CAFs are propitious to be further developed for biomedical applications such as drug delivery and wound care.

Nacre-Mimetic, Mechanically Flexible, and Electrically Conductive Silk Fibroin-MXene Composite Foams as Piezoresistive Pressure Sensors.

The hierarchical nacre-like three-dimensional (3D) assembly of porous and lightweight materials is in high demand for applications such as sensors, flexible energy storage and harvesting devices, electromagnetic interference shielding, and biomedical applications. However, designing such a biomimetic hierarchical architecture is highly challenging due to the lack of experimental approaches to achieve the necessary control over the materials' microstructure on the multilength scale. Aerogels and foam-based materials have recently been developed as attractive candidates for pressure-sensing applications. However, despite recent progress, the bottleneck for these materials to achieve electrical conductivity combined with high mechanical flexibility and fast strain recovery remains. In this study, for the first time, inspired by the multiscale architecture of nacre, we fabricated a series of ultra-lightweight, flexible, electrically conductive, and relatively high-strength composite foams through hybridizing the cross-linked silk fibroin (SF) biopolymer, extracted from Bombyx mori silkworm cocoon, reinforced with two-dimensional graphene oxide (GO) and Ti3C2 MXene nanosheets. Nacre is a naturally porous material with a lightweight, mechanically robust network structure, thanks to its 3D interconnected lamella-bridge micromorphology. Inspired by this material, we assemble a cross-linked SF fibrous solution with MXene and GO nanosheets into nacre-like architecture using a bidirectional freeze-casting technique. Subsequent freeze-drying and gas-phase hydrophobization resulted in composite foams with 3D hierarchical porous architectures with a unique combination of mechanical resilience, electrical conductance, and ultra-lightness. The developed composite presented excellent performances as piezoresistive pressure-sensing devices and sorbents for oil/water separation, which indicated great potential in mechanically switchable electronics.

Alteration of structural and mechanical properties of the temporomandibular joint disc following elastase digestion.

The temporomandibular joint disc is a fibrocartilaginous structure, composed of collagen fibers, elastin fibers, and proteoglycans. Despite the crucial role of elastin fibers in load-bearing properties of connective tissues, its contribution in temporomandibular joint disc biomechanics has been disregarded. This study attempts to characterize the structural-functional contribution of elastin in the temporomandibular joint disc. Using elastase, we selectively perturbed the elastin fiber network in porcine temporomandibular joint discs and investigated the structural, compositional, and mechanical regional changes through: (a) analysis of collagen and elastin fibers by immunolabeling and transmission electron microscopy; (b) quantitative analysis of collagen tortuosity, cell shape, and disc volume; (c) biochemical quantification of collagen, glycosaminoglycan and elastin content; and (d) cyclic compression test. Following elastase treatment, microscopic examination revealed fragmentation of elastin fibers across the temporomandibular joint disc, with a more pronounced effect in the intermediate regions. Also, biochemical analyses of the intermediate regions showed significant depletion of elastin (50%), and substantial decrease in collagen (20%) and glycosaminoglycan (49%) content, likely due to non-specific activity of elastase. Degradation of elastin fibers affected the homeostatic configuration of the disc, reflected in its significant volume enlargement accompanied by remarkable reduction of collagen tortuosity and cell elongation. Mechanically, elastase treatment nearly doubled the maximal energy dissipation across the intermediate regions while the instantaneous modulus was not significantly affected. We conclude that elastin fibers contribute to the restoration and maintenance of the disc resting shape and actively interact with collagen fibers to provide mechanical resilience to the temporomandibular joint disc.

Formation of cyclic structures in the cationic ring-opening polymerization of 1,3-dioxolane.

The cationic ring-opening polymerization of acetals is prone to cyclization of the polymer chains. This is also the case for the polymerization of 1,3-dioxolane. Literature states that this cyclization can be reduced by applying the Active Monomer mechanism, at least if no competition with the Active Chain End mechanism occurs. In this work, a detailed characterization of the different distributions resulting from the cationic ring-opening polymerization of 1,3-dioxolane via the Active Monomer mechanism is made by a combination of gel permeation chromatography, 1H NMR, and for the first time by matrix assisted laser desorption/ionization time of flight mass spectrometry. The influence of monomer addition speed, catalyst to initiator ratio and solvent were studied on both kinetics and composition of the product. Furthermore, it was found that increasing the conversion and monomer to initiator ratios leads to an increased amount of cyclic structures and to broader distributions, in correspondence with the Jacobson-Stockmayer theory. Furthermore, ion trapping experiments using 31P NMR provide insights into the actual reaction mechanism. Finally, purification of the products after the reactions led to a reduction of the cyclic fraction.

Differential Expression Profile of miR-27b, miR-29a, and miR-155 in Chronic Lymphocytic Leukemia and Breast Cancer Patients.

Over the past decade, studies on microRNA (miRNA) and cancer quickly became known. miRNAs are small non-coding RNAs that play a vital role in regulation of gene expression. In the present study, the expression of miR-27b, miR-29a, and miR-155, their prognostic roles, and their potential targets in chronic lymphocytic leukemia (CLL) and breast cancer (BC) by qRT-PCR were investigated. In two case-control studies, qRT-PCR was used to analyze the peripheral blood serum of 15 CLL patients and tissue samples of 15 BC patients for the expression of miR-27b, miR-29a, and miR-155. miRNA expression levels were calculated using the qRT-PCR method. The results revealed a significant increase in the expression of all miRNAs in patients with BC and CLL compared with respective healthy groups (p < 0.001). In BC patients, there was a significant difference between the expression of miR-155 and miR-29a (p < 0.05), miR-155 and miR-27b (p < 0.01), and miR-27b and miR-29a (p < 0.001). In CLL patients, a significant difference between expression of both miR-27b and miR-29a compared with expression of miR-155 (p < 0.001) was found. Furthermore, a significant association between miR-155 and prevascular invasion was found. Significantly, elevated circulating miRNAs were shown to be BC specific and could differentiate BC tissues from the controls. It was demonstrated that miRNAs used in this study and their expression profiles can be developed as biomarkers for early diagnosis and prognosis of CLL and BC. Further studies utilizing a larger test group of patients would provide identification of miRNAs as key players in intercellular interactions.

Evaluation of an elastic decellularized tendon-derived scaffold for the vascular tissue engineering application.

Due to the limited success rate of currently available vascular replacements, tissue engineering has received tremendous attention in recent years. A main challenge in the field of regenerative medicine is creating a mechanically functional tissue with a well-organized extracellular matrix, particularly of collagen and elastin. In this study, the native collagen scaffold derived from decellularized tendon sections, as a scaffold having the potential to be used for vascular tissue engineering applications, was studied. We showed that the elasticity of the scaffolds was improved when crosslinked with the bovine elastin. The effect of different concentrations of elastin on mechanical properties of the collagen scaffolds was evaluated of which 15% elastin concentration was selected for further analysis based on the results. Addition of 15% elastin to collagen scaffolds significantly decreased Young's modulus and the tensile stress at the maximum load and increased the tensile strain at the maximum load of the constructs as compared to those of the collagen scaffolds or control samples. Moreover, tubular elastin modified collagen scaffolds showed significantly higher burst pressure compared to the control samples. Smooth muscle cells and endothelial cells cultured on the elastin modified collagen scaffolds showed high viability (>80%) after 1, 3, and 7 days. Furthermore, the cells showed a high tendency to align with the collagen fibers within the scaffold and produced their own extracellular matrix over time. In conclusion, the results show that the decellularized tendon sections have a great potential to be used as scaffolds for vascular tissue engineering applications. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1225-1234, 2019.

The dynamic mechanical viscoelastic properties of the temporomandibular joint disc: The role of collagen and elastin fibers from a perspective of polymer dynamics.

The temporomandibular joint disc is a structure, characterized as heterogeneous fibrocartilage, and is composed of macromolecular biopolymers. Despite a large body of characterization studies, the contribution of matrix biopolymers on the dynamic viscoelastic behavior of the disc is poorly understood. Given the high permeability and low concentration of glycosaminoglycans in the disc, it has been suggested that poro-elastic behavior can be neglected and that the intrinsic viscoelastic nature of solid matrix plays a dominant role in governing its time-dependent behavior. This study attempts to quantify the contribution of collagen and elastin fibers to the viscoelastic properties of the disc. Using collagenase and elastase, we perturbed the collagen and elastin fibrillar network in porcine temporomandibular joint discs and investigated the changes of dynamic viscoelastic properties in five different regions of the disc. Following both treatments, the storage and loss moduli of these regions were reduced dramatically up to the point that the tissue was no longer mechanically heterogeneous. However, the proportion of changes in storage and loss moduli were different for each treatment, reflected in the decrease and increase of the loss tangent for collagenase and elastase treated discs, respectively. The reduction of storage and loss moduli of the disc correlated with a decrease of biopolymer length. The present study indicates that the compositional and structural changes of collagen and elastin fibers alter the viscoelastic properties of the disc consistent with polymer dynamics.