Wednesday, February 16, 2011

2/17 TERMSC

     
    TERMSC    
   
What we should know before using tissue engineering techniques to repair injured tendons: A developmental biology perspective.
February 16, 2011 at 2:46 AM
 

What we should know before using tissue engineering techniques to repair injured tendons: A developmental biology perspective.

Tissue Eng Part B Rev. 2011 Feb 11;

Authors: Liu CF, Aschbacher-Smith L, Barthelery N, Dyment N, Butler DL, Wylie C

Tendons connect muscles to bones, and serve as the transmitters of force that allow all the movements of the body. Tenocytes are the basic cellular units of tendons, and produce the collagens which form the hierarchical fiber system of the tendon. Tendon injuries are common, and difficult to repair, particularly in the case of the insertion of tendon into bone. Successful attempts at cell based repair therapies will require an understanding of the normal development of tendon tissues, including their differentiated regions such as the fibrous mid-section and fibrocartilaginous insertion site. Many genes are known to be involved in the formation of tendon. However, their functional roles in tendon development have not been fully characterized. Tissue engineers have attempted to generate functional tendon tissue in vitro. However, a lack of knowledge of normal tendon development has hampered these efforts. Here we review studies focusing on the developmental mechanisms of tendon development, and discuss the potential applications of a molecular understanding of tendon development to the treatment of tendon injuries.

PMID: 21314435 [PubMed - as supplied by publisher]

   
   
New approaches for the generation of induced pluripotent stem cells.
February 16, 2011 at 2:46 AM
 

New approaches for the generation of induced pluripotent stem cells.

Expert Opin Biol Ther. 2011 Feb 12;

Authors: Sidhu KS

Introduction: The advent of induced pluripotent stem cell (iPSC) technology has opened up new vistas to generate patient-specific pluripotent stem cells from somatic cells. During the last 5 years, the iPSCs produced from a variety of somatic cell sources are found to be very similar, if not identical to embryonic stem cells. Invariably these cells are produced by viral transduction of four transcriptional factors that renders these cells unfit for therapeutic purposes. Areas covered: This review discusses current developments emphasising on new and improved methods of generating iPSCs, including minimal or no genetic modifications via excisable lentiviral and transposon vectors or through repeated application of transient plasmid, episomal and adenovirus vectors. Recent use of small molecules, synthetic mRNA and microRNAs is also reviewed. Expert opinion: iPSC technology is emerging as an unprecedented opportunity in biomedical research, disease modeling, drug discovery and regenerative medicine. However, to harness the full potential of this technology, a number of issues that need to be resolved pertaining to iPSC safety, stability, culture variability, their comparison with ES cells, the reprogramming mechanisms and better ways to direct a specific reprogramming process including lineage specifications.

PMID: 21314494 [PubMed - as supplied by publisher]

   
   
BMP12 and BMP13 gene transfer induce ligamentogenic differentiation in mesenchymal progenitor and anterior cruciate ligament cells.
February 16, 2011 at 2:46 AM
 

BMP12 and BMP13 gene transfer induce ligamentogenic differentiation in mesenchymal progenitor and anterior cruciate ligament cells.

Cytotherapy. 2010 Jul;12(4):505-13

Authors: Haddad-Weber M, Prager P, Kunz M, Seefried L, Jakob F, Murray MM, Evans CH, Nöth U, Steinert AF

To date there are only very few data available on the ligamentogenic differentiation capacity of mesenchymal stromal/progenitor cells (MSC) and anterior cruciate ligament (ACL) fibroblasts.

PMID: 20334610 [PubMed - indexed for MEDLINE]

   
   
IL-2-controlled expression of multiple T cell trafficking genes and Th2 cytokines in the regulatory T cell-deficient scurfy mice: implication to multiorgan inflammation and control of skin and lung inflammation.
February 16, 2011 at 2:46 AM
 

IL-2-controlled expression of multiple T cell trafficking genes and Th2 cytokines in the regulatory T cell-deficient scurfy mice: implication to multiorgan inflammation and control of skin and lung inflammation.

J Immunol. 2011 Jan 15;186(2):1268-78

Authors: Sharma R, Sharma PR, Kim YC, Leitinger N, Lee JK, Fu SM, Ju ST

Scurfy (Sf) mice bear a mutation in the Foxp3 transcription factor, lack regulatory T cells (Treg), develop multiorgan inflammation, and die prematurely. The major target organs affected are skin, lungs, and liver. Sf mice lacking the Il2 gene (Sf.Il2(-/-)), despite being devoid of Treg, did not develop skin and lung inflammation, but the inflammation in liver, pancreas, submandibular gland, and colon remained. Genome-wide microarray analysis revealed hundreds of genes that were differentially regulated among Sf, Sf.Il2(-/-), and B6 CD4(+) T cells, but the most significant changes were those encoding receptors for trafficking/chemotaxis/retention and cytokines. Our study suggests that IL-2 controls the skin and lung inflammation in Sf mice in an apparent "organ-specific" manner through two novel mechanisms: by regulating the expression of genes encoding a variety of receptors for T cell trafficking/chemotaxis/retention and by regulating Th2 cell expansion and cytokine production. Thus, IL-2 is potentially a master regulator for multiorgan inflammation and an underlying etiological factor for various diseases associated with skin and lung inflammation.

PMID: 21169543 [PubMed - indexed for MEDLINE]

   
   
Polymeric endoaortic paving: Mechanical, thermoforming, and degradation properties of polycaprolactone/polyurethane blends for cardiovascular applications.
February 16, 2011 at 2:46 AM
 

Polymeric endoaortic paving: Mechanical, thermoforming, and degradation properties of polycaprolactone/polyurethane blends for cardiovascular applications.

Acta Biomater. 2011 Jan;7(1):287-94

Authors: Ashton JH, Mertz JA, Harper JL, Slepian MJ, Mills JL, McGrath DV, Vande Geest JP

Polymeric endoaortic paving (PEAP) is a process by which a polymer is endovascularly delivered and thermoformed to coat or "pave" the lumen of the aorta. This method may offer an improvement to conventional endoaortic therapy in allowing conformal graft application with reduced risk of endoleak and customization to complex patient geometries. Polycaprolactone (PCL)/polyurethane (PU) blends of various blend ratios were assessed as a potential material for PEAP by characterizing their mechanical, thermoforming and degradation properties. Biaxial tension testing revealed that the blends' stiffness is similar to that of aortic tissue, is higher for blends with more PCL content, and may be affected by thermoforming and degradation. Tubes of blends were able to maintain a higher diameter increase after thermoforming at higher PCL content and higher heating temperatures; 50/50 blend tubes heated to 55 °C were able to maintain 90% of the diameter increase applied. Delamination forces of the blends ranged from 41 to 235 N m⁻². In a Pseudomonas lipase solution, the 50/50 blend had a 94% lower degradation rate than pure PCL, and the 10/90 blend exhibited no degradation. These results indicate that PEAP, consisting of a PCL/PU blend, may be useful in developing the next generation of endoaortic therapy.

PMID: 20832506 [PubMed - indexed for MEDLINE]

   
   
In Vitro and In Vivo Degradation Profile of Aliphatic Polyesters Subjected to Electron Beam Sterilization.
February 16, 2011 at 2:46 AM
 

In Vitro and In Vivo Degradation Profile of Aliphatic Polyesters Subjected to Electron Beam Sterilization.

Acta Biomater. 2011 Feb 10;

Authors: Dånmark S, Finne-Wistrand A, Schander K, Hakkarainen M, Arvidson K, Mustafa K, Albertsson AC

Degradation characteristics in response to electron beam sterilization of designed and biodegradable aliphatic polyesters scaffolds are relevant for clinical successful synthetic graft tissue regeneration. Scaffold degradation in vitro and in vivo weredocumented and correlated to the macroscopic structure and chemical design of the original polymer. The materials tested were of inherently diverse hydrophobicity and crystallinity: poly(L-lactide) and random copolymers from L-lactide and ε-caprolactone or 1,5-dioxepan-2-one, fabricated into porous and non-porous scaffolds. After sterilization, the samples underwent hydrolysis in vitrofor up to a year. Invivo, scaffolds were surgically implanted into rat calvarial defects and retrieved for analysis after 28 and 91 days. In vitro, Poly(L-lactide-co-1,5-dioxepan-2-one) samples degraded most rapidly during hydrolysis, due to the pronounced chain-shortening reaction caused by the sterilization. Indicated by the rapidly decrease in mass and molecular weight of poly(LLA-co-DXO). Poly(L-Lactide-co-ε-caprolactone) samples were also strongly affected by sterilization, but mass loss was more gradual; molecular weight decreased rapidly during hydrolysis. Least affected by sterilization were the poly(L-lactide) samples, subsequently showing low mass loss rate and molecular weight decrease during hydrolysis. Mechanical stability varied greatly: poly(LLA-co-CL) withstood mechanical testing for up to 182 days, while poly(LLA) and poly(LLA-co-DXO) samples quickly became too brittle. Poly(LLA-co-DXO) samples unexpectedly degraded more rapidly in vivo than in vitro. After sterilization by electron beam irradiation, the three biodegradable polymers present widely diverse degradation profiles, both in vitro and in vivo. Each exhibits the potential to be tailored to meet diverse clinical tissue engineering requirements.

PMID: 21316490 [PubMed - as supplied by publisher]

   
   
Nano/micro electro-spun polyethylene terephthalate fibrous mat preparation and characterization.
February 16, 2011 at 2:46 AM
 

Nano/micro electro-spun polyethylene terephthalate fibrous mat preparation and characterization.

J Mech Behav Biomed Mater. 2011 Apr;4(3):340-51

Authors: Hadjizadeh A, Ajji A, Bureau MN

Electro-spun polyethylene terephthalate (PET) fibrous mats are potential substrates for biotechnological and biomedical applications. In this regard, substrate characteristics including, fiber diameter, orientation and mechanical properties play an important role in controlling the interaction of substrate with biological entities. However, few studies reporting the preparation of electro-spun PET substrates with such controlled characteristics have been published. In this study, electro-spun PET fibrous mats with fiber diameters in the nanometer and micrometer range were produced by varying polymer solution concentration and flow rate. Fiber orientation within the mats was also varied by varying collector surface velocities in rotation and translation. Their morphological, mechanical, thermal and structural properties were evaluated as a function of fiber diameter and collector speed using scanning electron microscopy (SEM), a micromechanical tester, differential scanning calorimetry (DSC) and X-ray diffraction (XRD), respectively. Varying polymer solution concentration and flow rate allowed the production of matrices with fiber diameters ranging from 400 nm to 2 μm. Tensile properties increased with fiber diameter and collector surface velocity. Thermal properties of electro-spun PET fibers were different from the structure of as received raw PET in the form of pellets, revealing an amorphous structure for the entire electro-spun PET. This was also confirmed by XRD analysis. No considerable differences were observed between electro-spun PET fibers, in terms of crystalline and thermal properties, produced under various conditions. These electro-spun mats with different fiber diameters, orientation and mechanical properties can be used for various applications including tissue engineering scaffolds.

PMID: 21316622 [PubMed - in process]

   
   
Xenogeneic extracellular matrix as an inductive scaffold for regeneration of a functioning musculotendinous junction.
February 16, 2011 at 2:46 AM
 

Xenogeneic extracellular matrix as an inductive scaffold for regeneration of a functioning musculotendinous junction.

Tissue Eng Part A. 2010 Nov;16(11):3309-17

Authors: Turner NJ, Yates AJ, Weber DJ, Qureshi IR, Stolz DB, Gilbert TW, Badylak SF

The prevailing dogma in tissue engineering is cell-centric. One shortcoming of this approach is the failure to provide the implanted cells with a suitable in vivo microenvironment that promotes tissue reconstruction. Extracellular matrix (ECM)-based scaffolds provide a three-dimensional microenvironment that can promote constructive and functional tissue remodeling rather than inflammation and scarring even in the absence of any implanted cells. The objective of this study was to determine the ability of an ECM-based scaffold to facilitate functional restoration of the distal gastrocnemius musculotendinous junction in a canine model after complete resection of the tissue. Within 6 months, vascularized, innervated skeletal muscle that was similar to normal muscle tissue had formed at the ECM-scaffold implantation site. This neo-tissue generated 48% of the contractile force of contralateral musculotendinous junction and represents the first report of de novo formation of contractile, vascularized, and innervated skeletal muscle in situ after significant tissue loss.

PMID: 20528669 [PubMed - indexed for MEDLINE]

   
   
BMHP1-Derived Self-Assembling Peptides: Hierarchically Assembled Structures with Self-Healing Propensity and Potential for Tissue Engineering Applications.
February 16, 2011 at 2:46 AM
 

BMHP1-Derived Self-Assembling Peptides: Hierarchically Assembled Structures with Self-Healing Propensity and Potential for Tissue Engineering Applications.

ACS Nano. 2011 Feb 11;

Authors: Gelain F, Silva D, Caprini A, Taraballi F, Natalello A, Villa O, Nam KT, Zuckermann RN, Doglia SM, Vescovi A

Self-assembling peptides (SAPs) are rapidly gaining interest as bioinspired scaffolds for cell culture and regenerative medicine applications. Bone Marrow Homing Peptide 1 (BMHP1) functional motif (PFSSTKT) was previously demonstrated to stimulate neural stem cell (NSC) viability and differentiation when linked to SAPs. We here describe a novel ensemble of SAPs, developed from the BMHP1 (BMHP1-SAPs), that spontaneously assemble into tabular fibers, twisted ribbons, tubes and hierarchical self-assembled sheets: organized structures in the nano- and microscale. Thirty-two sequences were designed and evaluated, including biotinylated and unbiotinylated sequences, as well as a hybrid peptide-peptoid sequence. Via X-ray diffraction (XRD), CD, and FTIR experiments we demonstrated that all of the BMHP1-SAPs share similarly organized secondary structures, that is, β-sheets and β-turns, despite their heterogeneous nanostructure morphology, scaffold stiffness, and effect over NSC differentiation and survival. Notably, we demonstrated the self-healing propensity of most of the tested BMHP1-SAPs, enlarging the set of potential applications of these novel SAPs. In in vitro cell culture experiments, we showed that some of these 10-mer peptides foster adhesion, differentiation, and proliferation of human NSCs. RGD-functionalized and hybrid peptide-peptoid self-assembling sequences also opened the door to BMHP1-SAP functionalization with further bioactive motifs, essential to tailor new scaffolds for specific applications. In in vivo experiments we verified a negligible reaction of the host nervous tissue to the injected and assembled BMHP1-SAP. This work will pave the way to the development of novel SAP sequences that may be useful for material science and regenerative medicine applications.

PMID: 21314189 [PubMed - as supplied by publisher]

   
   
Respiratory dialysis: Reduction in dependence on mechanical ventilation by venovenous extracorporeal CO2 removal*
February 16, 2011 at 2:46 AM
 

Respiratory dialysis: Reduction in dependence on mechanical ventilation by venovenous extracorporeal CO2 removal*

Crit Care Med. 2011 Feb 10;

Authors: Batchinsky AI, Jordan BS, Regn D, Necsoiu C, Federspiel WJ, Morris MJ, Cancio LC

OBJECTIVES:: Mechanical ventilation is injurious to the lung. Use of lung-protective strategies may complicate patient management, motivating a search for better lung-replacement approaches. We investigated the ability of a novel extracorporeal venovenous CO2 removal device to reduce minute ventilation while maintaining normocarbia. DESIGN:: Prospective animal study. SETTING:: Government laboratory animal intensive care unit. SUBJECTS:: Seven sedated swine. INTERVENTIONS:: Tracheostomy, volume-controlled mechanical ventilation, and 72 hrs of round-the-clock intensive care unit care. A 15-Fr dual-lumen catheter was inserted in the external jugular vein and connected to the Hemolung, an extracorporeal pump-driven venovenous CO2 removal device. Minute ventilation was reduced to maintain normocarbia (Paco2 35-45 mm Hg). Heparinization was maintained at an activated clotting time of 150-180 secs. MEASUREMENTS AND MAIN RESULTS:: Minute ventilation (L/min), CO2 removal by Hemolung (mL/min), Hemolung blood flow, O2 consumption (mL/min), CO2 production by the lung (mL/min), Paco2, and plasma-free hemoglobin (g/dL) were measured at baseline (where applicable), 2 hrs after device insertion, and every 6 hrs thereafter. Minute ventilation was reduced from 5.6 L/min at baseline to 2.6 L/min 2 hrs after device insertion and was maintained at 3 L/min until the end of the study. CO2 removal by Hemolung remained steady over 72 hrs, averaging 72 ± 1.2 mL/min at blood flows of 447 ± 5 mL/min. After insertion, O2 consumption did not change; CO2 production by the lung decreased by 50% and stayed at that level (p < .001). As the arterial PCO2 rose or fell, so did CO2 removal by Hemolung. Plasma-free hemoglobin did not change. CONCLUSIONS:: Venovenous CO2 removal enabled a 50% reduction in minute ventilation while maintaining normocarbia and may be an effective lung-protective adjunct to mechanical ventilation.

PMID: 21317644 [PubMed - as supplied by publisher]

   
   
In Vitro Manipulation of Endothelial Progenitor Cell Adhesion to Vascular Endothelium and Extracellular Matrix by the Phorbol Ester PMA.
February 16, 2011 at 2:46 AM
 

In Vitro Manipulation of Endothelial Progenitor Cell Adhesion to Vascular Endothelium and Extracellular Matrix by the Phorbol Ester PMA.

Artif Cells Blood Substit Immobil Biotechnol. 2011 Feb 11;

Authors: Powerski M, Henrich D, Sander A, Teiler A, Marzi I

Abstract: Injection of endothelial progenitor cells (EPCs) into arteries for cell therapy is a promising field in regenerative medicine. However, adhesion of EPCs during capillary passage is restricted, and non-adhering cells are lost into circulation. Here we demonstrate that it is possible to achieve a three- to sevenfold higher rate of EPC adhesion to endothelium and extracellular matrix molecules after short-term activation with phorbol myristate acetate (PMA). In addition, differentiation and toxicity analyses of PMA activated EPCs showed no impact on cell differentiation and negligible impact on cell survival.

PMID: 21314293 [PubMed - as supplied by publisher]

   
   
Stem cells therapy for retinal degeneration.
February 16, 2011 at 2:46 AM
 

Stem cells therapy for retinal degeneration.

Pak J Biol Sci. 2010 Nov 1;13(21):1016-22

Authors: Safari M

Stem cell therapy is widely considered as a therapeutic approach for retinal degeneration. Retinal injury results in permanent visual disturbance or blindness. Repair of such damage by stem cells is one of the most feasible types of central nervous system repair. In this review, we consider how stem cells might be optimized for use as donor cells. We discuss the benefits of stem cells for transplantation in retinal degenerative disease. A wide range of stem cells from different sources is being investigated for the treatment of retinal degeneration. This study reviews the recent and old achievements about stem cells for retinal repair.

PMID: 21313871 [PubMed - in process]

   
   
Yield and characterization of subcutaneous human adipose-derived stem cells by flow cytometric and adipogenic mRNA analyzes.
February 16, 2011 at 2:46 AM
 

Yield and characterization of subcutaneous human adipose-derived stem cells by flow cytometric and adipogenic mRNA analyzes.

Cytotherapy. 2010 Jul;12(4):538-46

Authors: Yu G, Wu X, Dietrich MA, Polk P, Scott LK, Ptitsyn AA, Gimble JM

Adipose-derived stromal/stem cells (ASC) capable of multipotential differentiation can be isolated with high yields from human subcutaneous lipoaspirates. This study reports our recent experience of isolating and immunophenotypically characterizing ASC from >60 human patients with a mean age of 43.6 and body mass index (BMI) of 27.

PMID: 20380539 [PubMed - indexed for MEDLINE]

   
   
Drug-Carrier/Hydrogel Scaffold for Controlled Growth of Cells.
February 16, 2011 at 2:46 AM
 

Drug-Carrier/Hydrogel Scaffold for Controlled Growth of Cells.

Eur J Pharm Biopharm. 2011 Feb 10;

Authors: Wei L, Lin J, Cai C, Fang Z, Fu W

In this work, a novel functional drug-carrier/hydrogel scaffold was prepared to control the growth of cells for tissue engineering. The drug-carrier/hydrogel scaffold was constructed from a micelle/Ca-alginate microparticles (Alg-MPs)/poly(vinyl alcohol) (PVA) hydrogel composite. In such a system, paclitaxel (PTX) is encapsulated in the micelles formed by poly(L-glutamic acid)-b-poly(propylene oxide)-b-poly(L-glutamic acid) (GPG), while human vascular endothelial growth factor-165 (VEGF(165)) is loaded in the Alg-MPs. The designed function of this scaffold is to encourage the fast growth of cells such as endothelial cells (ECs) in the early period to reduce the rejection, and inhibit the growth of cells such as smooth muscle cells (SMCs) in late period to prevent the vascular intimal hyperplasia. The effect of VEGF(165) is to encourage the growth of ECs, while PTX is used to inhibit the growth of smooth muscle cells (SMCs). Structure characterizations show that the drug carriers are well dispersed in the PVA hydrogel. Independent release behaviors of the two drugs are observed. VEGF(165) shows a short-term release behavior while PTX shows a long-term release behavior from the drug-carrier/hydrogel scaffolds. Further study shows a controllable cell growth behavior on this functional drug-carrier/hydrogel scaffold via the MTT assay.

PMID: 21316449 [PubMed - as supplied by publisher]

   
   
Osteoconductive properties of poly(96L/4D-lactide)/beta-tricalcium phosphate in long term animal model.
February 16, 2011 at 2:46 AM
 

Osteoconductive properties of poly(96L/4D-lactide)/beta-tricalcium phosphate in long term animal model.

Biomaterials. 2011 Feb 9;

Authors: Daculsi G, Goyenvalle E, Cognet R, Aguado E, Suokas EO

The objective of this study was to determine the effect of calcium phosphate mineral content on the bone in-growth at the expense of composite of co-polylactide polymer charged with 2 different ratios of β-TCP granules (10 and 24 w-% of β-TCP). The evaluation was realized in a long term rabbit bone model. After 24, 48 and 76 weeks, the implants were examined by micro CT, scanning electron microscopy (SEM) using backscattered electron (BSE) and light microscopy (polarized and blue light microscopy). No foreign body reaction was detected during the 76 weeks follow-up in any of the test samples. Polymer hydrolysis began at approximately 24 weeks, by 76 weeks, the pure polymer implant had begun to release P(96L/4D)LA particles and show signs of peripheral localized bone resorption. A decrease in the amount of CaP was noticed between 24 and 76 weeks in both 10 wt-% and 24 wt-% β-TCP/P(96L/4D)LA composites. The study showed that the highest bone in-growth was with 24 wt-% β-TCP/P(96L/4D)LA composite. Bone in-growth and mineralization were evident for the composites associated with specific peripheral bone architecture. Fluorescent labelling demonstrated high bone in-growth and remodeling at the interface, while for pure co-polymer no bone remodeling or bone activity was maintained after 48 weeks. The study demonstrated the positive effect of calcium phosphate content into P(96L/4D)LA. This kind of composite is a suitable resorbable osteoconductive matrix, which provides long term stability required for ligament fixation device.

PMID: 21315446 [PubMed - as supplied by publisher]

   
   
In pursuit of the newt.
February 16, 2011 at 2:46 AM
 

In pursuit of the newt.

IEEE Pulse. 2011 Jan-Feb;2(1):26-33

Authors: Campbell S

It looks like a frog-but with a tail. Its legs are as long as its arms. Some live in water, and some are semiaquatic, returning to water to breed. But perhaps what's most noteworthy about the newt is its remarkable ability to bounce back from what would be catastrophic injuries to other creatures. Front leg munched off by a predator? Another leg will grow in its place. Eye poked out by a fast-moving branch? The newt can fix that too. Even more complicated organs are not beyond the regenerative capacities of the little newt: intestines, spinal cord, and even heart can be recovered. It's superhero material and, more close to home, it's a model that researchers in regenerative medicine are not beyond aspiring to. Dr. Cato Laurencin was heard earlier this year encouraging his colleagues at the Annual Society for Biomaterials Conference to bring out the inner newt in all of us. Newts may be phylogenetically much lower than humans, but in the areas of regenerative medicine and tissue engineering, advances in research have propelled us to the point that we might, in fact, aspire to newtness-before us lies the possibility and project of figuring out how we too might grow an entire limb or repair whole organs at the site of injury.

PMID: 21317064 [PubMed - in process]

   
   
Cardiac Arrhythmias Induced by Chloral Hydrate in Rhesus Monkeys.
February 16, 2011 at 2:46 AM
 

Cardiac Arrhythmias Induced by Chloral Hydrate in Rhesus Monkeys.

Cardiovasc Toxicol. 2011 Feb 13;

Authors: Han P, Song H, Yang P, Xie H, Kang YJ

Chloral hydrate has been long used as a safe sedative and hypnotic drug in humans. However, reports on its cardiovascular adverse effects have been published from time to time. The present study was undertaken to use Rhesus monkeys as a model to define the dose regiment of chloral hydrate at which cardiac arrhythmias can be induced and the consequences of the cardiac events. Male Rhesus monkeys of 2-3 years old were intravenously infused with chloral hydrate starting at 50 mg/kg with an increasing increment of 25 mg/kg until the occurrence of cardiac arrhythmias. In addition, a traditional up-and-down dosing procedure was applied to define a single dose level at which cardiac arrhythmias can be induced. The data obtained showed that when the sequentially escaladed dose reached 125 mg/kg, cardiac arrhythmias occurred in all monkeys tested. The single effective dose to cause cardiac arrhythmias calculated from the crossover analysis was 143 ± 4 mg/kg. This value would be equivalent to 68.6 ± 1.9 mg/kg for children and 46.4 ± 1.3 mg/kg for adults in humans. Under either multiple or single dose condition, cardiac arrhythmias did not occur before 40 min after the onset of anesthesia induced by chloral hydrate. Cardiac arrhythmias were recovered without help at the end of the anesthesia in most cases, but also continued after the regain of consciousness in some cases. The cardiac arrhythmias were accompanied with compromised cardiac function including suppressed fractional shortening and ejection fraction. This study thus suggests that cautions need to be taken when chloral hydrate is used above certain levels and beyond a certain period of anesthesia, and cardiac arrhythmias induced by chloral hydrate need to be closely monitored because compromised cardiac function may occur simultaneously. In addition, patients with cardiac arrhythmias induced by chloral hydrate should be monitored even after they are recovered from the anesthesia.

PMID: 21318465 [PubMed - as supplied by publisher]

   
   
The decellularized vascular allograft as an experimental platform for developing a biocompatible small-diameter graft conduit in a rat surgical model.
February 16, 2011 at 2:46 AM
 

The decellularized vascular allograft as an experimental platform for developing a biocompatible small-diameter graft conduit in a rat surgical model.

Yonsei Med J. 2011 Mar 1;52(2):227-33

Authors: Hwang SJ, Kim SW, Choo SJ, Lee BW, Im IR, Yun HJ, Lee SK, Song H, Cho WC, Lee JW

Purpose: The present study was aimed to assess the feasibility of using decellularized aortic allograft in a rat small animal surgical model for conducting small diameter vascular tissue engineering research. Materials and Methods: Decellularized aortic allografts were infra-renally implanted in 12 Sprague-Dawley (SD) adult rats. The conduits were harvested at 2 (n = 6) and 8 weeks (n = 6), and assessed by hematoxylin and eosin (H&E), van Gieson, Masson Trichrome staining, and immunohistochemistry for von Willebrand factor, CD 31(+), and actin. Results: Consistent, predictable, and reproducible results were produced by means of a standardized surgical procedure. All animals survived without major complications. Inflammatory immune reaction was minimal, and there was no evidence of aneurysmal degeneration or rupture of the decellularized vascular implants. However, the aortic wall appeared thinner and the elastic fibers in the medial layer showed decreased undulation compared to the normal aorta. There was also minimal cellular repopulation of the vascular media. The remodeling appeared progressive from 2 to 8 weeks with increased intimal thickening and accumulation of both collagen and cells staining for actin. Although the endothelial like cells appeared largely confluent at 8 weeks, they were not as concentrated in appearance as in the normal aorta. Conclusion: The results showed the present rat animal model using decellularized vascular allograft implants to be a potentially durable and effective experimental platform for conducting further research on small diameter vascular tissue engineering.

PMID: 21319339 [PubMed - in process]

   
   
A hybrid biomimetic nanomatrix composed of electrospun polycaprolactone and bioactive peptide amphiphiles for cardiovascular implants.
February 16, 2011 at 2:46 AM
 

A hybrid biomimetic nanomatrix composed of electrospun polycaprolactone and bioactive peptide amphiphiles for cardiovascular implants.

Acta Biomater. 2011 Jan;7(1):225-33

Authors: Andukuri A, Kushwaha M, Tambralli A, Anderson JM, Dean DR, Berry JL, Sohn YD, Yoon YS, Brott BC, Jun HW

Current cardiovascular therapies are limited by the loss of endothelium, restenosis and thrombosis. The goal of this study was to develop a biomimetic hybrid nanomatrix that combined the unique properties of electrospun polycaprolactone (ePCL) nanofibers with self-assembled peptide amphiphiles (PAs). ePCL nanofibers have interconnected nanoporous structures, but are hampered by a lack of surface bioactivity to control cellular behavior. It has been hypothesized that PAs could self-assemble onto the surface of ePCL nanofibers and endow them with the characteristic properties of native endothelium. The PAs, which comprised hydrophobic alkyl tails attached to functional hydrophilic peptide sequences, contained enzyme-mediated degradable sites coupled to either endothelial cell-adhesive ligands (YIGSR) or polylysine (KKKKK) nitric oxide (NO) donors. Two different PAs (PA-YIGSR and PA-KKKKK) were successfully synthesized and mixed in a 90:10 (YK) ratio to obtain PA-YK. PA-YK was reacted with pure NO to develop PA-YK-NO, which was then self-assembled onto ePCL nanofibers to generate a hybrid nanomatrix, ePCL-PA-YK-NO. Uniform coating of self-assembled PA nanofibers on ePCL was confirmed by transmission electron microscopy. Successful NO release from ePCL-PA-YK-NO was observed. ePCL-YK and ePCL-PA-YK-NO showed significantly increased adhesion of human umbilical vein endothelial cells (HUVECs). ePCL-PA-YK-NO also showed significantly increased proliferation of HUVECs and reduced smooth muscle cell proliferation. ePCL-PA-YK-NO also displayed significantly reduced platelet adhesion compared with ePCL, ePCL-PA-YK and a collagen control. These results indicate that this hybrid nanomatrix has great potential application in cardiovascular implants.

PMID: 20728588 [PubMed - indexed for MEDLINE]

   
   
Single cell transcriptional profiling reveals heterogeneity of human induced pluripotent stem cells.
February 16, 2011 at 2:46 AM
 

Single cell transcriptional profiling reveals heterogeneity of human induced pluripotent stem cells.

J Clin Invest. 2011 Feb 7;

Authors: Narsinh KH, Sun N, Sanchez-Freire V, Lee AS, Almeida P, Hu S, Jan T, Wilson KD, Leong D, Rosenberg J, Yao M, Robbins RC, Wu JC

Human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) are promising candidate cell sources for regenerative medicine. However, despite the common ability of hiPSCs and hESCs to differentiate into all 3 germ layers, their functional equivalence at the single cell level remains to be demonstrated. Moreover, single cell heterogeneity amongst stem cell populations may underlie important cell fate decisions. Here, we used single cell analysis to resolve the gene expression profiles of 362 hiPSCs and hESCs for an array of 42 genes that characterize the pluripotent and differentiated states. Comparison between single hESCs and single hiPSCs revealed markedly more heterogeneity in gene expression levels in the hiPSCs, suggesting that hiPSCs occupy an alternate, less stable pluripotent state. hiPSCs also displayed slower growth kinetics and impaired directed differentiation as compared with hESCs. Our results suggest that caution should be exercised before assuming that hiPSCs occupy a pluripotent state equivalent to that of hESCs, particularly when producing differentiated cells for regenerative medicine aims.

PMID: 21317531 [PubMed - as supplied by publisher]

   
   
Diels-Alder Click Cross-Linked Hyaluronic Acid Hydrogels for Tissue Engineering.
February 16, 2011 at 2:46 AM
 

Diels-Alder Click Cross-Linked Hyaluronic Acid Hydrogels for Tissue Engineering.

Biomacromolecules. 2011 Feb 11;

Authors: Nimmo CM, Owen SC, Shoichet MS

Hyaluronic acid (HA) is a naturally occurring polymer that holds considerable promise for tissue engineering applications. Current cross-linking chemistries often require a coupling agent, catalyst, or photoinitiator, which may be cytotoxic, or involve a multistep synthesis of functionalized-HA, increasing the complexity of the system. With the goal of designing a simpler one-step, aqueous-based cross-linking system, we synthesized HA hydrogels via Diels-Alder "click" chemistry. Furan-modified HA derivatives were synthesized and cross-linked via dimaleimide poly(ethylene glycol). By controlling the furan to maleimide molar ratio, both the mechanical and degradation properties of the resulting Diels-Alder cross-linked hydrogels can be tuned. Rheological and degradation studies demonstrate that the Diels-Alder click reaction is a suitable cross-linking method for HA. These HA cross-linked hydrogels were shown to be cytocompatible and may represent a promising material for soft tissue engineering.

PMID: 21314111 [PubMed - as supplied by publisher]

   
   
Effect of molecular weight of chitosan degraded by microwave irradiation on lyophilized scaffold for bone tissue engineering applications.
February 16, 2011 at 2:46 AM
 

Effect of molecular weight of chitosan degraded by microwave irradiation on lyophilized scaffold for bone tissue engineering applications.

J Biomed Mater Res A. 2011 Feb 11;

Authors: Mecwan MM, Rapalo GE, Mishra SR, Haggard WO, Bumgardner JD

Chitosan (CTS) is biocompatible, biodegradable, and can be formed into 3D porous structures for bone tissue engineering applications. Although studies have reported on the effects of molecular weight (MW) on CTS physicochemical properties, studies evaluating CTS biological property relationships often do not account for MW that confounds interpretation of study results. The aim of this study was to evaluate the effect of MW on CTS physicochemical and biological properties. CTS materials were treated for 6, 18, and 30 min by microwave irradiation to decrease MW without affecting deacetylation (DDA). Materials were evaluated for crystallinity using X-ray diffraction, thermal degradation using differential scanning calorimetry, water content, swelling ratio, and in vitro compatibility using Saos-2. Results showed that microwave treatments did not affect DDA but decreased MW and swelling ratio by 45.78% and 36.75%, respectively, after 30 min of microwave treatment. Microwave-treated CTS showed reduced or no crystalline peaks. Initial increase in exothermic peak temperatures with short (6 min) microwave treatment times were followed by a decrease with longer (18 and 30 min) treatment times. Cell growth over 7 days on samples was proportional to MW with the number of cells being 62% higher on CTS with the highest MW (3.71 ± 0.25 × 10(5) g/mol) when compared with the lower MW CTS (2.38 ± 0.12 × 10(5) g/mol). These results demonstrate the importance of MW of CTS to both its physicochemical characteristics and biological properties, providing researchers with another tool for the modulation and optimization of CTS for different biomedical applications. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.

PMID: 21319294 [PubMed - as supplied by publisher]

   
   
Adrenal extracellular matrix scaffolds support adrenocortical cell proliferation and function in vitro.
February 16, 2011 at 2:46 AM
 

Adrenal extracellular matrix scaffolds support adrenocortical cell proliferation and function in vitro.

Tissue Eng Part A. 2010 Nov;16(11):3363-74

Authors: Allen RA, Seltz LM, Jiang H, Kasick RT, Sellaro TL, Badylak SF, Ogilvie JB

Transplantation of functional adrenal cortex cells could reduce morbidity and increase the quality of life of patients with adrenal insufficiency. Our aim was to determine whether adrenal extracellular matrix (ECM) scaffolds promote adrenocortical cell endocrine function and proliferation in vitro. We seeded decellularized porcine adrenal ECM with primary human fetal adrenocortical (HFA) cells. Adrenocortical function was quantified by cortisol secretion of HFA-ECM constructs after stimulation with adrenocorticotropic hormone. Proliferation was assessed by adenosine triphosphate assay. HFA-ECM construct morphology was evaluated by immunofluorescence microscopy and scanning electron microscopy. Adrenal HFA-ECM constructs coated with laminin were compared to uncoated constructs. Laminin coating did not significantly affect HFA morphology, proliferation, or function. We demonstrated HFA cell attachment to adrenal ECM scaffolds. Cortisol production and HFA cell proliferation were significantly increased in HFA-ECM constructs compared to controls (p < 0.05), and cortisol secretion rate per cell is comparable to that of human adult and fetal explants. We conclude that adrenal ECM supports endocrine function and proliferation of adrenocortical cells in vitro. Adrenal ECM scaffolds may form the basis for biocompatible tissue-engineered adrenal replacements.

PMID: 20528677 [PubMed - indexed for MEDLINE]

   
   
Osteogenic comparison of expanded and uncultured adipose stromal cells.
February 16, 2011 at 2:46 AM
 

Osteogenic comparison of expanded and uncultured adipose stromal cells.

Cytotherapy. 2010 Jul;12(4):554-62

Authors: Cheung WK, Working DM, Galuppo LD, Leach JK

Adipose stromal cells (ASC) are a promising alternative to progenitor cells from other tissue compartments because of their multipotential and capacity to retrieve significantly more progenitor cells. Initial cell samples are heterogeneous, containing a collection of cells that may contribute to tissue repair, but the sample becomes more homogeneous with each passage. Therefore, we hypothesized that the osteogenic potential of culture-expanded ASC would differ from uncultured ASC.

PMID: 20370353 [PubMed - indexed for MEDLINE]

   
   
Translational potential of human embryonic and induced pluripotent stem cells for myocardial repair: insights from experimental models.
February 16, 2011 at 2:46 AM
 

Translational potential of human embryonic and induced pluripotent stem cells for myocardial repair: insights from experimental models.

Thromb Haemost. 2010 Jul 5;104(1):30-8

Authors: Kong CW, Akar FG, Li RA

Heart diseases have been a major cause of death worldwide, including developed countries. Indeed, loss of non-regenerative, terminally differentiated cardiomyocytes (CMs) due to aging or diseases is irreversible. Current therapeutic regimes are palliative in nature, and in the case of end-stage heart failure, transplantation remains the last resort. However, this option is significantly hampered by a severe shortage of donor cells and organs. Human embryonic stem cells (hESCs) can self-renew while maintaining their pluripotency to differentiate into all cell types. More recently, direct reprogramming of adult somatic cells to become pluripotent hES-like cells (a.k.a. induced pluripotent stem cells or iPSCs) has been achieved. The availability of hESCs and iPSCs, and their successful differentiation into genuine human heart cells have enabled researchers to gain novel insights into the early development of the human heart as well as to pursue the revolutionary paradigm of heart regeneration. Here we review our current knowledge of hESC-/iPSC-derived CMs in the context of two fundamental operating principles of CMs (i.e. electrophysiology and Ca2+-handling), the resultant limitations and potential solutions in relation to their translation into clinical (bioartificial pacemaker, myocardial repair) and other applications (e.g. as models for human heart disease and cardiotoxicity screening).

PMID: 20539906 [PubMed - indexed for MEDLINE]

   
   
Heart valve tissue engineering: quo vadis?
February 16, 2011 at 2:46 AM
 

Heart valve tissue engineering: quo vadis?

Curr Opin Biotechnol. 2011 Feb 9;

Authors: Schoen FJ

Surgical replacement of diseased heart valves by mechanical and tissue valve substitutes is now commonplace and generally enhances survival and quality of life. However, a fundamental problem inherent to the use of existing mechanical and biological prostheses in the pediatric population is their failure to grow, repair, and remodel. A tissue engineered heart valve could, in principle, accommodate these requirements, especially somatic growth. This review provides a brief overview of the field of heart valve tissue engineering, with emphasis on recent studies and evolving concepts, especially those that establish design criteria and key hurdles that must be surmounted before clinical implementation.

PMID: 21315575 [PubMed - as supplied by publisher]

   
   
Hybrid adipogenic implants from adipose stem cells for soft tissue reconstruction in vivo.
February 16, 2011 at 2:46 AM
 

Hybrid adipogenic implants from adipose stem cells for soft tissue reconstruction in vivo.

Tissue Eng Part A. 2010 Nov;16(11):3299-307

Authors: Moioli EK, Chen M, Yang R, Shah B, Wu J, Mao JJ

A critical barrier in tissue regeneration is scale-up. Bioengineered adipose tissue implants have been limited to ∼10  mm in diameter. Here, we devised a 40-mm hybrid implant with a cellular layer encapsulating an acellular core. Human adipose-derived stem cells (ASCs) were seeded in alginate. Poly(ethylene)glycol-diacrylate (PEGDA) was photopolymerized into 40-mm-diameter dome-shaped gel. Alginate-ASC suspension was painted onto PEGDA surface. Cultivation of hybrid constructs ex vivo in adipogenic medium for 28 days showed no delamination. Upon 4-week in vivo implantation in athymic rats, hybrid implants well integrated with host subcutaneous tissue and could only be surgically separated. Vascularized adipose tissue regenerated in the thin, painted alginate layer only if ASC-derived adipogenic cells were delivered. Contrastingly, abundant fibrous tissue filled ASC-free alginate layer encapsulating the acellular PEGDA core in control implants. Human-specific peroxisome proliferator-activated receptor-γ (PPAR-γ) was detected in human ASC-seeded implants. Interestingly, rat-specific PPAR-γ was absent in either human ASC-seeded or ASC-free implants. Glycerol content in ASC-delivered implants was significantly greater than that in ASC-free implants. Remarkably, rat-specific platelet/endothelial cell adhesion molecule (PECAM) was detected in both ASC-seeded and ASC-free implants, suggesting anastomosis of vasculature in bioengineered tissue with host blood vessels. Human nuclear staining revealed that a substantial number of adipocytes were of human origin, whereas endothelial cells of vascular wall were of chemaric human and nonhuman (rat host) origins. Together, hybrid implant appears to be a viable scale-up approach with volumetric retention attributable primarily to the acellular biomaterial core, and yet has a biologically viable cellular interface with the host. The present 40-mm soft tissue implant may serve as a biomaterial tissue expander for reconstruction of lumpectomy defects.

PMID: 20528671 [PubMed - indexed for MEDLINE]

   
   
Cellular analysis by open-source software for affordable cytometry.
February 16, 2011 at 2:46 AM
 

Cellular analysis by open-source software for affordable cytometry.

Scanning. 2011 Feb 11;

Authors: Mittag A, Pinto FE, Endringer DC, Tarnok A, Lenz D

Image cytometry is an important technique in affordable healthcare and cellular research. Some efforts toward establishing a personal, low-cost cytometer have been described in the literature. However, a self-assembled fluorescence microscope requires software for cytometric analysis. There are some open-source image-based software analysis applications available. However, for a quantitative analysis of images, software that can generate data comparable to those of previously evaluated cytometric analyses programs is required. Hence, the aim of this study is to compare results of a commercially available image cytometry program to data obtained using the open-source software CellProfiler (CP). Leukocytes and fluorescent bead images obtained using a Laser Scanning Cytometer were analyzed by CP and the results compared with those of conventional cytometric analyses' programs. Algorithms were developed enabling the analysis of leukocytes and beads by CP. CP provided similar results to those obtained by the cytometer software. Hallmark parameters, including cell count and fluorescence intensity, revealed a high correlation in the analysis of both programs. Therefore, CP is appropriate for cellular analysis on a self-assembled microscope, thereby enabling affordable cytometry. SCANNING 33: 1-8, 2011. © 2011 Wiley Periodicals, Inc.

PMID: 21319173 [PubMed - as supplied by publisher]

   
   
Methods for forming human microvascular tubes in vitro and measuring their macromolecular permeability.
February 16, 2011 at 2:46 AM
 

Methods for forming human microvascular tubes in vitro and measuring their macromolecular permeability.

Methods Mol Biol. 2011;671:281-93

Authors: Price GM, Tien J

This chapter describes a protocol for forming open endothelial tubes in vitro and quantifying their permeability to macromolecules. These tubes consist of confluent monolayers of human microvascular endothelial cells in perfused microfluidic collagen gels. The cylindrical geometry of the tubes mimics the shape of microvessels in vivo; it allows simultaneous and/or repeated measurements of permeability coefficients and detection of focal leaks. We have used these in vitro models to test the effects of agonists on microvascular permeability and are developing arrays of microvascular tubes to enable large-scale testing.

PMID: 20967637 [PubMed - indexed for MEDLINE]

   
   
Large-scale cultivation of transplantable dermal papilla cellular aggregates using microfabricated PDMS arrays.
February 16, 2011 at 2:46 AM
 

Large-scale cultivation of transplantable dermal papilla cellular aggregates using microfabricated PDMS arrays.

Acta Biomater. 2011 Jan;7(1):315-24

Authors: Hsieh CH, Wang JL, Huang YY

In this work we have developed a strategy for cultivating dermal papilla (DP) cells to form multiple arrayed spheroidal microtissues for transplantation on a micropatterned polydimethylsiloxane (PDMS)-based tissue culture polystyrene (TCPS) plate system. We also describe the behavior of dermal papilla cells on this platform and the spontaneous formation of spheroidal microtissues by DP cells. We used a hydrophobic PDMS arrayed chip as a master to separate the seeded cells in the TCPS culture plate. By controlling the cell seeding densities, a microwell with arrayed DP spheroidal microtissues was easily formed. Formation of DP microtissues was associated with overlapping multilayered cells on the microwells and low cell-substrate adhesivity on the PDMS film. The microwell environment enhanced the aggregation of DP cells into spheroidal microtissues on the TCPS culture plate. The spheroidal microtissues preserved their hair induction potential in vitro and in vivo. A large quantity of DP spheroidal microtissues could be obtained rapidly and simply using this platform. We could harvest hundreds of DP microtissues (352 microtissues) with a cell seeding density of 1×10⁶ cells well⁻¹ after 3 days cultivation in one well of a 24-well plate. This is the first demonstration of the formation of DP spheres in large quantitites.

PMID: 20728585 [PubMed - indexed for MEDLINE]

   
   
A multilayered synthetic human elastin/polycaprolactone hybrid vascular graft with tailored mechanical properties.
February 16, 2011 at 2:46 AM
 

A multilayered synthetic human elastin/polycaprolactone hybrid vascular graft with tailored mechanical properties.

Acta Biomater. 2011 Jan;7(1):295-303

Authors: Wise SG, Byrom MJ, Waterhouse A, Bannon PG, Ng MK, Weiss AS

Small-diameter synthetic vascular graft materials fail to match the patency of human tissue conduits used in vascular bypass surgery. The foreign surface retards endothelialization and is highly thrombogenic, while the mismatch in mechanical properties induces intimal hyperplasia. Using recombinant human tropoelastin, we have developed a synthetic vascular conduit for small-diameter applications. We show that tropoelastin enhances endothelial cell attachment (threefold vs. control) and proliferation by 54.7 ± 1.1% (3 days vs. control). Tropoelastin, when presented as a monomer and when cross-linked into synthetic elastin for biomaterials applications, had low thrombogenicity. Activation of the intrinsic pathway of coagulation, measured by plasma clotting time, was reduced for tropoelastin (60.4 ± 8.2% vs. control). Platelet attachment was also reduced compared to collagen. Reductions in platelet interactions were mirrored on cross-linked synthetic elastin scaffolds. Tropoelastin was subsequently incorporated into a synthetic elastin/polycaprolactone conduit with mechanical properties optimized to mimic the human internal mammary artery, including permeability, compliance, elastic modulus and burst pressure. Further, this multilayered conduit presented a synthetic elastin internal lamina to circulating blood and demonstrated suturability and mechanical durability in a small scale rabbit carotid interposition model.

PMID: 20656079 [PubMed - indexed for MEDLINE]

   
   
Magnetic resonance imaging evaluation of remodeling by cardiac elastomeric tissue scaffold biomaterials in a rat model of myocardial infarction.
February 16, 2011 at 2:46 AM
 

Magnetic resonance imaging evaluation of remodeling by cardiac elastomeric tissue scaffold biomaterials in a rat model of myocardial infarction.

Tissue Eng Part A. 2010 Nov;16(11):3395-402

Authors: Stuckey DJ, Ishii H, Chen QZ, Boccaccini AR, Hansen U, Carr CA, Roether JA, Jawad H, Tyler DJ, Ali NN, Clarke K, Harding SE

Grafting of elastomeric biomaterial scaffolds may offer a radical strategy for the prevention of heart failure after myocardial infarction by increasing efficacy of stem cell delivery as well as acting as mechanical restraint devices to constrain scar expansion. Biomaterials can be partially optimized in vitro, but their in vivo performance is most critical and should ideally be monitored serially and noninvasively. We used magnetic resonance imaging (MRI) to assess three scaffold materials with a range of structural moduli equal to or greater than myocardial tissue: poly(glycerol sebacate) (PGS), poly(ethyleneterephathalate)/dimer fatty acid (PED), and TiO(2)-reinforced PED (PED-TiO(2)). Patches, 1  cm in diameter, were grafted onto the hearts of infarcted rats, with biomaterial-free infarcted rat hearts used as controls. MRI was able to determine scaffold size and location on the heart and identified unexpectedly rapid in vivo degradation of the PGS compared with previous in vitro testing. PED patches did not withstand in vivo attachment, but the more rigid PED-TiO(2) material was detrimental to heart function, increasing chamber and scar sizes and reducing ejection fractions compared with controls. In contrast, the mechanically compatible PGS scaffold successfully reduced hypertrophy, giving it potential for limiting excessive postinfarct remodeling. PGS was unable to support systolic function, but it would be suitable for strategies to deliver cardiac stem/progenitor cells, to limit remodeling during the period of functional cellular integration, and to degrade after cell assimilation by the heart. This work has also shown for the first time the value of using MRI as a noninvasive tool for evaluating and optimizing therapeutic biomaterials in vivo.

PMID: 20528670 [PubMed - indexed for MEDLINE]

   
   
Getting beneath the skin to understand MSC complexity.
February 16, 2011 at 2:46 AM
 

Getting beneath the skin to understand MSC complexity.

Cytotherapy. 2010 Jul;12(4):438-9

Authors: Dominici M, Horwitz EM

PMID: 20608761 [PubMed - indexed for MEDLINE]

   
   
10(th) annual meeting of the Safety Pharmacology Society: an overview.
February 16, 2011 at 2:46 AM
 

10(th) annual meeting of the Safety Pharmacology Society: an overview.

Expert Opin Drug Saf. 2011 Feb 14;

Authors: Cavero I

The 10(th) annual meeting of the Safety Pharmacology (SP) Society covered numerous topics of educational and practical research interest. Biopolymers - the theme of the keynote address - were presented as essential components of medical devices, diagnostic tools, biosensors, human tissue engineering and pharmaceutical formulations for optimized drug delivery. Toxicology and SP investigators - the topic of the Distinguished Service Award Lecture - were encouraged to collaborate in the development of SP technologies and protocols applicable to toxicology studies. Pharmaceutical companies, originally organizations bearing all risks for developing their portfolios, are increasingly moving towards fully integrated networks which outsource core activities (including SP studies) to large contract research organizations. Future nonclinical data are now expected to be of such high quality and predictability power that they may obviate the need for certain expensive and time-consuming clinical investigations. In this context, SP is called upon to extend its risk assessment purview to areas which currently are not systematically covered, such as drug-induced QRS interval prolongation, negative emotions and feelings (e.g., depression), and minor chronic cardiovascular and metabolic changes (e.g., as produced by drugs for type 2 diabetes) which can be responsible for delayed morbidity and mortality. The recently approved ICH S9 guidance relaxes the traditional regulatory SP package in order to accelerate the clinical access to anticancer drugs for patients with advanced malignancies. The novel FDA 'Animal Rule' guidance proposes that for clinical candidates with well-understood toxicities, marketing approval may be granted exclusively on efficacy data generated in animal studies as human clinical investigations for these types of drugs are either unfeasible or unethical. In conclusion, the core messages of this meeting are that SP should consistently operate according to the 'fit-for-purpose' principle and gradually integrate new mechanism-oriented safety paradigms into the traditional ones for ensuring more effectively the safety of drugs for any population of patients in need.

PMID: 21314442 [PubMed - as supplied by publisher]

   
   
A multiphase model for tissue construct growth in a perfusion bioreactor.
February 16, 2011 at 2:46 AM
 

A multiphase model for tissue construct growth in a perfusion bioreactor.

Math Med Biol. 2010 Jun;27(2):95-127

Authors: O'Dea RD, Waters SL, Byrne HM

The growth of a cell population within a rigid porous scaffold in a perfusion bioreactor is studied, using a three-phase continuum model of the type presented by Lemon et al. (2006, Multiphase modelling of tissue growth using the theory of mixtures. J. Math. Biol., 52, 571-594) to represent the cell population (and attendant extracellular matrix), culture medium and porous scaffold. The bioreactor system is modelled as a 2D channel containing the cell-seeded rigid porous scaffold (tissue construct) which is perfused with culture medium. The study concentrates on (i) the cell-cell and cell-scaffold interactions and (ii) the impact of mechanotransduction mechanisms on construct composition. A numerical and analytical analysis of the model equations is presented and, depending upon the relative importance of cell aggregation and repulsion, markedly different cell movement is revealed. Additionally, mechanotransduction effects due to cell density, pressure and shear stress-mediated tissue growth are shown to generate qualitative differences in the composition of the resulting construct. The results of our simulations indicate that this model formulation (in conjunction with appropriate experimental data) has the potential to provide a means of identifying the dominant regulatory stimuli in a cell population.

PMID: 19805485 [PubMed - indexed for MEDLINE]

   
   
Electrospun fiber mats containing shikonin and derivatives with potential biomedical applications.
February 16, 2011 at 2:46 AM
 

Electrospun fiber mats containing shikonin and derivatives with potential biomedical applications.

Int J Pharm. 2011 Feb 10;

Authors: Kontogiannopoulos KN, Assimopoulou AN, Tsivintzelis I, Panayiotou C, Papageorgiou VP

Alkannin, Shikonin (A/S) and their derivatives are naturally occurring hydroxynaphthoquinones with a well-established spectrum of wound healing, antimicrobial, anti-inflammatory, antioxidant and antitumor activity. Clinical studies over the years revealed that A/S derivatives-based wound healing preparations (such as HELIXDERM(®)) are among a very small group of therapeutics that modulate both the inflammatory and proliferative phases of wound healing and present significant tissue regenerative activity. The purpose of the present work was to combine the biological properties of A/S and the advantages of electrospun meshes to prepare a potent topical/transdermal biomaterial for A/S. Four biocompatible polymers (cellulose acetate, poly(L-lactide), poly(lactide-co-glycolide) LA/GA:50/50 and 75/25) were used for the first time, to produce electrospun fiber mats containing either shikonin or A/S mixture in various amounts. Both drugs were effectively loaded into the above biomaterials. The incorporation of drugs did not considerably affect fibers morphology and their mean diameter size varied from 315 to 670nm. High drug entrapment efficiencies (ranged from 74% to 95%) and appropriate release profiles were achieved, that render these fibers as potential A/S topical/transdermal wound healing dressings. Given the multifunctional activity of the natural products alkannins and shikonins, their consideration as bioactive constituents for tissue engineering scaffolds seems a promising strategy for repairing and regenerating tissues and mainly skin.

PMID: 21316431 [PubMed - as supplied by publisher]

   
   
Two pole air gap electrospinning: Fabrication of highly aligned, three-dimensional scaffolds for nerve reconstruction.
February 16, 2011 at 2:46 AM
 

Two pole air gap electrospinning: Fabrication of highly aligned, three-dimensional scaffolds for nerve reconstruction.

Acta Biomater. 2011 Jan;7(1):203-15

Authors: Jha BS, Colello RJ, Bowman JR, Sell SA, Lee KD, Bigbee JW, Bowlin GL, Chow WN, Mathern BE, Simpson DG

We describe the structural and functional properties of three-dimensional (3D) nerve guides fabricated from poly-ε-caprolactone (PCL) using the air gap electrospinning process. This process makes it possible to deposit nano-to-micron diameter fibers into linear bundles that are aligned in parallel with the long axis of a cylindrical construct. By varying starting electrospinning conditions it is possible to modulate scaffold material properties and void space volume. The architecture of these constructs provides thousands of potential channels to direct axon growth. In cell culture functional assays, scaffolds composed of individual PCL fibers ranging from 400 to 1500 nm supported the penetration and growth of axons from rat dorsal root ganglion. To test the efficacy of our guide design we reconstructed 10mm lesions in the rodent sciatic nerve with scaffolds that had fibers 1 μm in average diameter and void volumes >90%. Seven weeks post implantation, microscopic examination of the regenerating tissue revealed dense, parallel arrays of myelinated and non-myelinated axons. Functional blood vessels were scattered throughout the implant. We speculate that end organ targeting might be improved in nerve injuries if axons can be directed to regenerate along specific tissue planes by a guide composed of 3D fiber arrays.

PMID: 20727992 [PubMed - indexed for MEDLINE]

   
   
A novel spatially designed and functionally graded electrospun membrane for periodontal regeneration.
February 16, 2011 at 2:46 AM
 

A novel spatially designed and functionally graded electrospun membrane for periodontal regeneration.

Acta Biomater. 2011 Jan;7(1):216-24

Authors: Bottino MC, Thomas V, Janowski GM

A periodontal membrane with a graded structure allows tailoring of the layer properties to design a material system that will retain its physical, chemical and mechanical characteristics for a period long enough to optimize periodontal regeneration. In this work a novel functionally graded membrane (FGM) was designed and fabricated via sequential multilayer electrospinning. The FGM consists of a core layer (CL) and two functional surface layers (SLs) interfacing with bone (nano-hydroxyapatite, n-HAp) and epithelial (metronidazole, MET) tissues. The CL comprises a neat poly(DL-lactide-co-ε-caprolactone) (PLCL) layer surrounded by two composite layers composed of a protein/polymer ternary blend (PLCL:PLA:GEL). Electrospinning parameters involved in fabrication of the individual layers (i.e. neat PLCL, ternary blend, PLA:GEL+10%n-HAp and PLA:GEL+25%MET) were optimized to obtain fibrous layers free of beads. Morphology, structure and mechanical property studies were carried out on each electrospun layer. The individual fiber morphology and roughness of the functional SLs, which are the n-HAp containing and drug-incorporating layers were evaluated by atomic force microscopy. The CL structure demonstrated higher strength (8.7 MPa) and a more elastic behavior (strain at break 357%) compared with the FGM (3.5 MPa, 297%). Incorporation of n-HAp to enhance osteoconductive behavior and MET to combat periodontal pathogens led to a novel FGM that holds promise at solving the drawbacks of currently available membranes.

PMID: 20801241 [PubMed - indexed for MEDLINE]

   
   
Engineering an in vitro model of a functional ligament from bone to bone.
February 16, 2011 at 2:46 AM
 

Engineering an in vitro model of a functional ligament from bone to bone.

Tissue Eng Part A. 2010 Nov;16(11):3515-25

Authors: Paxton JZ, Grover LM, Baar K

For musculoskeletal tissues that transmit loads during movement, the interfaces between tissues are essential to minimizing injury. Therefore, the reproduction of functional interfaces within engineered musculoskeletal tissues is critical to the successful transfer of the technology to the clinic. The goal of this work was to rapidly engineer ligament equivalents in vitro that contained both the soft tissue sinew and a hard tissue bone mimetic. This goal was achieved using cast brushite (CaHPO(4)·2H(2)O) anchors to mimic bone and a fibrin gel embedded with fibroblasts to create the sinew. The constructs formed within 7 days. Fourteen days after seeding, the interface between the brushite and sinew could withstand a stress of 9.51 ± 1.7  kPa before failure and the sinew reached a Young's modulus value of 0.16 ± 0.03  MPa. Treatment with ascorbic acid and proline increased the collagen content of the sinew (from 1.34% ± 0.2% to 8.34% ± 0.37%), strength of the interface (29.24 ± 6  kPa), and modulus of the sinew (2.69 ± 0.25  MPa). Adding transforming growth factor-β resulted in a further increase in collagen (11.25% ± 0.39%), interface strength (42 ± 8  kPa), and sinew modulus (5.46 ± 0.68  MPa). Both scanning electron and Raman microscopy suggested that the interface between the brushite and sinew mimics the in vivo tidemark at the enthesis. This work describes a major step toward the development of tissue-engineered ligaments for the repair of ligament ruptures in humans.

PMID: 20593972 [PubMed - indexed for MEDLINE]

   
   
Methods for the Identification, Characterization and Banking of Human DPSCs: Current Strategies and Perspectives.
February 16, 2011 at 2:46 AM
 

Methods for the Identification, Characterization and Banking of Human DPSCs: Current Strategies and Perspectives.

Stem Cell Rev. 2011 Feb 12;

Authors: Tirino V, Paino F, d'Aquino R, Desiderio V, De Rosa A, Papaccio G

Dental pulp stem cells (DPSCs), originating from neural crests, can be found within dental pulp. Up to now, it has been demonstrated that these cells are capable of producing bone tissue, both in vitro and in vivo and differentiate into adipocytes, endotheliocytes, melanocytes, neurons, glial cells, and can be easily cryopreserved and stored. Moreover, recent attention has been focused on tissue engineering and on the properties of these cells. In addition, adult bone tissue with good vascularisation has been obtained in grafts. The latest use in clinical trials for bone repair enforces the notion that DPSCs can be used successfully in patients. Therefore, their isolation, selection, differentiation and banking is of great importance. The isolation and detection techniques used in most laboratories are based on the use of antibodies revealed by flow-cytometers with cell sorter termed FACS (fluorescent activated cell sorter). In this report, we focus our attention on the main procedures used in the selection of DPSCs by flow cytometry, cell culture, freezing/thawing, cell cycle evaluation, histochemistry/immunofluorescence and differentiation of DPSCs. In addition, new methods/protocols to select and isolate stem cells without staining by fluorescent markers for implementation in biomedical/clinical laboratories are discuss. We emphasize that the new methods must address simplicity and short times of preparation and use of samples, complete sterility of cells, the potential disposable, low cost and complete maintenance of the viability and integrity of the cells with real-time response for subsequent applications in the biomedical/clinical/surgical fields.

PMID: 21318597 [PubMed - as supplied by publisher]

   
   
Public, Researchers, Industry Left in Dark on CIRM Chair Selection Criteria
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Has CIRM Funded Stem Cell Research that Bush Would Have Banned?
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Stem Cell Directors Meet Next Thursday to Deal With Klein Replacement
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Okarma's Departure, Pfizer and More
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