Biomedical subjects

Xuejun Wen

Publications and source records attributed to Xuejun Wen.

12 recordsLinked to original sources

PubMed2007

Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues.

Periostin is predominantly expressed in collagen-rich fibrous connective tissues that are subjected to constant mechanical stresses including: heart valves, tendons, perichondrium, cornea, and the periodontal ligament (PDL). Based on these data we hypothesize that periostin can regulate collagen I fibrillogenesis and thereby affect the biomechanical properties of connective tissues. Immunoprecipitation and immunogold transmission electron microscopy experiments demonstrate that periostin is capable of directly interacting with collagen I. To analyze the potential role of periostin in collagen I fibrillogenesis, gene targeted mice were generated. Transmission electron microscopy and morphometric analyses demonstrated reduced collagen fibril diameters in skin dermis of periostin knockout mice, an indication of aberrant collagen I fibrillogenesis. In addition, differential scanning calorimetry (DSC) demonstrated a lower collagen denaturing temperature in periostin knockout mice, reflecting a reduced level of collagen cross-linking. Functional biomechanical properties of periostin null skin specimens and atrioventricular (AV) valve explant experiments provided direct evidence of the role that periostin plays in regulating the viscoelastic properties of connective tissues. Collectively, these data demonstrate for the first time that periostin can regulate collagen I fibrillogenesis and thereby serves as an important mediator of the biomechanical properties of fibrous connective tissues.

Adenoviridae↗

PubMed2006

Cardiac neural crest ablation inhibits compaction and electrical function of conduction system bundles.

Retroviral and transgenic lineage-tracing studies have shown that neural crest cells associate with the developing bundles of the ventricular conduction system. Whereas this migration of cells does not provide progenitors for the myocardial cells of the conduction system, the question of whether neural crest affects the differentiation and/or function of cardiac specialized tissues continues to be of interest. Using optical mapping of voltage-sensitive dye, we determined that ventricles from chick embryos in which the cardiac neural crest had been laser ablated did not progress to apex-to-base activation by the expected stage [i.e., Hamburger and Hamilton (HH) 35] but instead maintained basal breakthroughs of epicardial activation consistent with immature function of the conduction system. In direct studies of activation, waves of depolarization originating from the His bundle were found to be uncommon in control hearts from HH34 and HH35 embryos. However, activations propagating from septal base, at or near the His bundle, occurred frequently in hearts from HH34 and HH35 neural crest-ablated embryos. Consistent with His bundle cells maintaining electrical connections with adjacent working myocytes, histological analyses of hearts from neural crest-ablated embryos revealed His bundles that had not differentiated a lamellar organization or undergone a process of compaction and separation from surrounding myocardium observed in controls. Furthermore, measurements on histological sections from optically mapped hearts indicated that, whereas His bundle diameter in control embryos thinned by almost one-half between HH30 and HH34, the His bundle in ablated embryos underwent no such compaction in diameter, maintaining a thickness at HH30, HH32, and HH34 similar to that observed in HH30 controls. We conclude that the cardiac neural crest is required in a novel function involving lamellar compaction and electrical isolation of the basally located His bundle from surrounding myocardium.

Animals↗

PubMed2006

Proteomics and genomics of microgravity.

Many serious adverse physiological changes occur during spaceflight. In the search for underlying mechanisms and possible new countermeasures, many experimental tools and methods have been developed to study microgravity caused physiological changes, ranging from in vitro bioreactor studies to spaceflight investigations. Recently, genomic and proteomic approaches have gained a lot of attention; after major scientific breakthroughs in the fields of genomics and proteomics, they are now widely accepted and used to understand biological processes. Understanding gene and/or protein expression is the key to unfolding the mechanisms behind microgravity-induced problems and, ultimately, finding effective countermeasures to spaceflight-induced alterations. Significant progress has been made in identifying the genes/proteins responsible for these changes. Although many of these genes and/or proteins were observed to be either upregulated or downregulated, however, no large-scale genomics and proteomics studies have been published so far. This review aims at summarizing the current status of microgravity-related genomics and proteomics studies and stimulating large-scale proteomics and genomics research activities.

Animals↗

PubMed2006

Fabrication and characterization of permeable degradable poly(DL-lactide-co-glycolide) (PLGA) hollow fiber phase inversion membranes for use as nerve tract guidance channels.

Biodegradable permeable poly(DL-lactide-co-glycolide) (PLGA) hollow fiber membranes (HFMs) were fabricated using a wet phase inversion technique. By varying several parameters, such as the spinneret size, solvent and non-solvent pair, polymer concentration, flow rate, precipitation method, drop height, and small molecular pore-forming agents, PLGA HFMs with variable sizes, surface morphologies, porosities, and diffusive permeability were obtained. Under simulated physiological conditions in vitro, PLGA HFMs exhibited a degradation profile to accommodate nervous system regeneration and axonal outgrowth. While accelerated degradation resulted in substantial molecular weight loss starting at 2 weeks and loss of selective permeability at 3 weeks, PLGA HFMs maintained gross structural integrity in the first 4 weeks, followed by sharp weight loss at 6 weeks and complete disappearance at about 8 weeks. When compared to the raw PLGA material in a pellet form, which underwent heterogeneous degradation, the PLGA HFMs exhibited a homogeneous degradation where the surface and bulk degraded at approximately the same rate, and an overall lower degradation rate. Our results indicate that using a wet phase inversion technique, degradable HFMs with variable size, inner and outer surface morphologies, porosity, and permeability with potential applications for nerve tract guidance conduits can be fabricated.

Animals↗

PubMed2006

Effect of filament diameter and extracellular matrix molecule precoating on neurite outgrowth and Schwann cell behavior on multifilament entubulation bridging device in vitro.

At present there is no clinically effective treatment for injuries or pathological processes that disrupt the continuity of axons in the mature central nervous system. However, a number of studies suggest that a tremendous potential exists for developing biomaterial based therapies. In particular, biomaterials in the form of bridging substrates have been shown to support at least some level of axonal regeneration across the lesion site, but display a limited capacity for directing axons toward their targets. To improve the directionality and outgrowth rate of the axonal regeneration process, filaments and tubes appear promising, but the technology is far from optimized. As a step toward optimization, the influence of filament diameter and various extracellular matrix coatings on nerve regeneration was evaluated in this article using a dorsal root ganglion (DRG) explant model. An increasing pattern of alignment and outgrowth of neurites in the direction parallel the long axis of the packed filament bundles with decreasing filament diameters ranging from supracellular and beyond (500 to 100 mum), cellular (30 mum), down to subcellular size (5 mum) was observed. Such effects became most prominent on filament bundles with individual filament diameters in the range of cellular size and below (5 and 30 mum) where highly directional and robust neuronal outgrowth was achieved. In addition, laminin-coated filaments that approached the size of spinal axons support significantly longer regenerative outgrowth than similarly treated filaments of larger diameter, and exceed outgrowth distance on similarly sized filaments treated with fibronectin. These data suggested the feasibility of using a multifilament entubulation bridging device for supporting directional axonal regeneration.

Acrylic Resins↗

PubMed2006

Research project: Charleston Bioengineered Kidney Project.

The goal of Charleston Bioengineered Kidney Project is to engineer a functional living human kidney suitable for surgical implantation using principles of directed tissue self-assembly and tissue fusion. This is a multidisciplinary project which incorporates multiple innovative bioengineering technologies and expertise from a broad spectrum of disciplines. The conceptual framework, engineering principles, design, potential cell source as well as the first preliminary data demonstrating the feasibility of the proposed Charleston Bioengineered Kidney Project are outlined. The potential challenges are described. Finally, the experts' opinion about the proposed project is also presented.

Animals↗

PubMed2006

Improving the elasticity and cytophilicity of biodegradable polyurethane by changing chain extender.

Two types of biodegradable polyurethanes (PUs) were synthesized from methylene di-p-phenyl-diisocyanate (MDI), polycaprolactone diol (PCL-diol), and chain extenders of either butanediol (BD) or 2,2'-(methylimino)diethanol (MIDE). The effects of two types of chain extenders on the degradation, mechanical properties, hydrophilicity, and cytophilicity of PUs were evaluated. In vitro degradation studies showed that PU containing MIDE has a higher degradation rate than PU synthesized using BD as a chain extender. Mechanical testing on dry and wet samples demonstrated that PU containing MIDE has a much higher elongation in the elastic region than PU containing BD. PU containing MIDE is more hydrophilic and retains more liquid during in vitro culture. Furthermore, preliminary cytocompatibility studies showed that both types of degradable PU are nontoxic, and fibroblasts adhere better and proliferate faster on MIDE containing PU than BD containing PU. To compare the cytocompatibility and degradation behaviors of the synthesized PU with existing FDA approved biocompatible material, polylactide (PLA), with a similar degradation rate, was used as negative control. Two types of PU were shown to have similar cytocompatibility and degradation behaviors as those of the PLA material. To verify the effectiveness of the cytotoxicity assay, latex was used as a positive control. Latex samples showed toxicity to cultured cells as expected. In conclusion, by changing the type of chain extender used during the synthesis of degradable PUs, the degradation rate, mechanical properties, hydrophilicity, and cytophilicity can be adjusted for different tissue engineering applications.

Absorbable Implants↗

PubMed2006

Cardiovascular tissue engineering I. Perfusion bioreactors: a review.

Tissue engineering is a fast-evolving field of biomedical science and technology with future promise to manufacture living tissues and organs for replacement, repair, and regeneration of diseased organs. Owing to the specific role of hemodynamics in the development, maintenance, and functioning of the cardiovascular system, bioreactors are a fundamental of cardiovascular tissue engineering. The development of perfusion bioreactor technology for cardiovascular tissue engineering is a direct sequence of previous historic successes in extracorporeal circulation techniques. Bioreactors provide a fluidic environment for tissue engineered tissue and organs, and guarantee their viability, maturation, biomonitoring, testing, storage, and transportation. There are different types of bioreactors and they vary greatly in their size, complexity, and functional capabilities. Although progress in design and functional properties of perfusion bioreactors for tissue engineered blood vessels, heart valves, and myocardial patches is obvious, there are some challenges and insufficiently addressed issues, and room for bioreactor design improvement and performance optimization. These challenges include creating a triple perfusion bioreactor for vascularized tubular tissue engineered cardiac construct; designing and manufacturing fluidics-based perfused minibioreactors; incorporation of systematic mathematical modeling and computer simulation based on computational fluid dynamics into the bioreactor designing process; and development of automatic systems of hydrodynamic regime control. Designing and engineering of built-in noninvasive biomonitoring systems is another important challenge. The optimal and most efficient perfusion and conditioning regime, which accelerates tissue maturation of tissue-engineered constructs also remains to be determined. This is a first article in a series of reviews on critical elements of cardiovascular tissue engineering technology describing the current status, unsolved problems, and challenges of bioreactor technology in cardiovascular tissue engineering and outlining future trends and developments.

Bioreactors↗

PubMed2005

Fabrication of semipermeable hollow fiber membranes with highly aligned texture for nerve guidance.

In order to improve the guidance potential of a nerve entubulation bridging device, highly aligned textures were formed on the inner surface of semipermeable hollow fiber membranes (HFMs) during the wet phase inversion process. By precisely controlling the fabrication parameters, such as polymer solution flow rate, coagulant solution flow rate, and the air-gap distance, also called drop height, different-sized aligned grooves can be fabricated on the inner surface of HFMs. Preliminary studies using in vitro dorsal root ganglion (DRG) regeneration assay showed that both the alignment and outgrowth rate of regenerating axons increased significantly on HFMs with aligned textures compared to those on HFMs with a smooth inner surface. Studies in progress are evaluating axonal outgrowth and regeneration using in vivo sciatic-nerve and spinal-cord-injury models.

Animals↗

PubMed2005

Tissue-engineering approaches for axonal guidance.

Owing to the profound impact of nervous system damage, extensive studies have been carried out aimed at facilitating axonal regeneration following injury. Tissue engineering, as an emerging and rapidly growing field, has received extensive attention for nervous system axonal guidance. Numerous engineered substrates containing oriented extracellular matrix molecules, cells or channels have displayed potential of supporting axonal regeneration and functional recovery. Most attempts are focused on seeking new biomaterials, new cell sources, as well as novel designs of tissue-engineered neuronal bridging devices, to generate safer and more efficacious neuronal tissue repairs.

Animals↗

PubMed2004

Resorption rate and biocompatibility characteristics of two polyester ventilation tubes in a guinea pig model.

OBJECTIVES: Determine the resorption rate and biocompatibility characteristics of 2 polyester ventilation tubes, and to determine whether soap and water exposure accelerates polyester tube degradation. STUDY DESIGN AND SETTING: 50/50 poly (D, L-lactide-co-glycolide; PLGA-50) and poly (L-lactide; PLA) polymers were placed into the tympanic membranes of Hartley pigmented guinea pigs. Integrity of the tubes was determined by weekly otoscopic examination. Biocompatibility was assessed by comparing auditory brainstem response (ABR) thresholds and by examining tympanic membrane changes following tube resorption. Shah minigrommet ventilation tubes were used as controls. In the second portion of this study, implanted PLGA-50 and PLA tubes were exposed weekly to a mixture of soap and water (1:5) until complete resorption was observed. Biocompatibility was assessed by periodic ABR testing and tympanic membrane examination. RESULTS: The PLA tubes remained in the tympanic membrane for a longer period (63.2 +/- 19.3 days) than the PLGA-50 (18.8 +/- 8.1 days). The tympanic membrane and resorbable tube interface demonstrated equivalent findings for auditory thresholds and tissue histopathology at the implant site compared to nonresorbable controls. The resorption behavior was not altered by exposure to soap and water. Tympanic membranes of all animals following tube degradation and soap water exposure were intact with minimal scarring and no signs of persistent foreign body response. The histological analysis showed that implantation of resorbable tubes was not accompanied by secondary infection with otorrhea through the tube, did not result in a permanent perforation or dislocation of the tube into the middle ear cavity, and was not followed by excess tympanosclerosis or localized or diffuse membrane atrophy. CONCLUSIONS AND SIGNIFICANCE: Resorbable polyester pressure equalization tubes demonstrate predictable resorption behavior and similar biocompatibility characteristics when compared with nonresorbable Shah minigrommet ventilation tubes. Exposure to soap water does not accelerate polyester tube degradation nor change the host tissue response during the indwelling period or after complete resorption. The data suggests that resorbable ventilation tubes are substantially equivalent to other FDA-approved tympanostomy devices with regard to safety and biocompatibility in the guinea pig model examined and may provide improved clinical performance by combining this approach with sustained release technology. EBM RATING: B-2.

Animals↗

PubMed2003

[Phosphorus transfer between mixed poplar and black locust seedlings].

In this paper, the 32P radio-tracer technique was applied to study the ways of phosphorus transfer between poplar (Populus euramericana cv. 'I-214') and black locust (Robinia pseudoacacia). A five compartment root box (18 cm x 18 cm x 26 cm) was used for testing the existence of the hyphal links between the roots of two tree species when inoculated with vesicular-arbuscular (VA) mycorrhizal fungus (Glomus mosseae). Populus I-214 (donor) and Robinia pseudoacacia (receiver) were grown in two terminal compartments, separated by a 2 cm root-free soil layer. The root compartments were lined with bags of nylon mesh (38 microns) that allowed the passage of hyphae but not roots. The top soil of a mixed stand of poplar and black locust, autoclaved at 121 degrees C for one hour, was used for growing seedlings for testing. In 5 compartment root box, mycorrhizal root colonization of poplar was 34%, in which VA mycorrhizal fungus was inoculated, whereas 26% mycorrhizal root colonization was observed in black locust, the other terminal compartment, 20 weeks after planting. No root colonization was observed in non-inoculated plant pairs. This indicated that the mycorrhizal root colonization of black locust was caused by hyphal spreading from the poplar. Test of tracer isotope of 32P showed that the radioactivity of the treatment significantly higher than that of the control (P < 0.05), 14 days from the tracer applied, to 27 days after, when VA mycorrhizal fungus was inoculated in poplar root. Furthermore, mycorrhizal interconnections between the roots of poplar and black locust seedlings was observed in situ by binocular in root box. All these experiments showed that the hyphal links was formed between the roots of two species of trees inoculated by VA mycorrhizal fungus. Four treatments were designed according to if there were two nets (mesh 38 microns), 2 cm apart, between the poplar and black locust, and if the soil in root box was pasteurized. Most significant differences of radioactivity among four treatments appeared 44 days after feeding 32P, the radioactivity of the day was applied to estimating the contribution of the various possible transfer ways to the total amount of nutrient transfer. Level of 32P radioactivity was found to be significantly (P < 0.05) higher in leaves of the treatment of "no separated and soil non-pasteurized" (17.1 pulse.g-1.s-1) than in leaves of "net separated and soil non-pasteurized" (5.3 pulse.g-1.s-1), and also significantly higher in leaves of "no net separated and soil pasteurized" (11.5 pulse.g.s-1) than in leaves of "net separated and soil pasteurized" (2.3 pulse.g-1.s-1), and very significantly (P < 0.01) higher in leaves of "no net separated and soil non-pasteurized" than in leaves of "net separated and soil pasteurized", whereas the levels of 32P radioactivity were not significantly different between the other treatments. The results showed that root contact and root exudations were the main ways of phosphorus transfer between the two species and the amount of phosphorus transfer through these two ways accounted for 62% of the total. The activity of the microorganisms including VA mycorrhizal fungi and the interaction between the microorganisms and root contact and root exudations made up 38% of total amount of phosphorus. The effect of mycorrhizal hyphal links in the direct nutrient transfer between poplar and black locust through separate mesh (38 microns) was little.

Biological Transport↗