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Monday, 2 July 2012
Researchers improve living tissues with 3-D printed vascular networks made from sugar
Researchers improve living tissues with 3-D printed vascular networks made from sugar
Monday, July 2, 2012Researchers are hopeful that new advances in tissue engineering and regenerative medicine could one day make a replacement liver from a patient's own cells, or animal muscle tissue that could be cut into steaks without ever being inside a cow. Bioengineers can already make 2D structures out of many kinds of tissue, but one of the major roadblocks to making the jump to 3D is keeping the cells within large structures from suffocating; organs have complicated 3D blood vessel networks that are still impossible to recreate in the laboratory.
Now, University of Pennsylvania researchers have developed an innovative solution to this perfusion problem: they've shown that 3D printed templates of filament networks can be used to rapidly create vasculature and improve the function of engineered living tissues.
The research was conducted by a team led by postdoctoral fellow Jordan S. Miller and Christopher S. Chen, the Skirkanich Professor of Innovation in the Department of Bioengineering at Penn, along with Sangeeta N. Bhatia, Wilson Professor at the Massachusetts Institute of Technology, and postdoctoral fellow Kelly R. Stevens in Bhatia's laboratory.
Their work was published in the journal Nature Materials.
Without a vascular system ? a highway for delivering nutrients and removing waste products ? living cells on the inside of a 3D tissue structure quickly die. Thin tissues grown from a few layers of cells don't have this problem, as all of the cells have direct access to nutrients and oxygen. Bioengineers have therefore explored 3D printing as a way to prototype tissues containing large volumes of living cells.
The most commonly explored techniques are layer-by-layer fabrication, or bioprinting, where single layers or droplets of cells and gel are created and then assembled together one drop at a time, somewhat like building a stack of LEGOs.
Such "additive manufacturing" methods can make complex shapes out of a variety of materials, but vasculature remains a major challenge when printing with cells. Hollow channels made in this way have structural seams running between the layers, and the pressure of fluid pumping through them can push the seams apart. More important, many potentially useful cell types, like liver cells, cannot readily survive the rigors of direct 3D bioprinting.
To get around this problem, Penn researchers turned the printing process inside out.
Rather than trying to print a large volume of tissue and leave hollow channels for vasculature in a layer-by-layer approach, Chen and colleagues focused on the vasculature first and designed free-standing 3D filament networks in the shape of a vascular system that sat inside a mold. As in lost-wax casting, a technique that has been used to make sculptures for thousands of years, the team's approach allowed for the mold and vascular template to be removed once the cells were added and formed a solid tissue enveloping the filaments.
"Sometimes the simplest solutions come from going back to basics," Miller said. "I got the first hint at this solution when I visited a Body Worlds exhibit, where you can see plastic casts of free-standing, whole organ vasculature."
This rapid casting technique hinged on the researchers developing a material that is rigid enough to exist as a 3D network of cylindrical filaments but which can also easily dissolve in water without toxic effects on cells. They also needed to make the material compatible with a 3D printer so they could make reproducible vascular networks orders of magnitude faster, and at larger scale and higher complexity, than possible in a layer-by-layer bioprinting approach.
After much testing, the team found the perfect mix of material properties in a humble material: sugar. Sugars are mechanically strong and make up the majority of organic biomass on the planet in the form of cellulose, but their building blocks are also typically added and dissolved into nutrient media that help cells grow.
"We tested many different sugar formulations until we were able to optimize all of these characteristics together," Miller said. "Since there's no single type of gel that's going to be optimal for every kind of engineered tissue, we also wanted to develop a sugar formula that would be broadly compatible with any cell type or water-based gel."
The formula they settled on ? a combination of sucrose and glucose along with dextran for structural reinforcement ? is printed with a RepRap, an open-source 3D printer with a custom-designed extruder and controlling software. An important step in stabilizing the sugar after printing, templates are coated in a thin layer of a degradable polymer derived from corn. This coating allows the sugar template to be dissolved and to flow out of the gel through the channels they create without inhibiting the solidification of the gel or damaging the growing cells nearby. Once the sugar is removed, the researchers start flowing fluid through the vascular architecture and cells begin to receive nutrients and oxygen similar to the exchange that naturally happens in the body.
The whole process is quick and inexpensive, allowing the researchers to switch with ease between computer simulations and physical models of multiple vascular configurations.
"This new platform technology, from the cell's perspective, makes tissue formation a gentle and quick journey," Chen said, "because cells are only exposed to a few minutes of manual pipetting and a single step of being poured into the molds before getting nourished by our vascular network."
The researchers showed that human blood vessel cells injected throughout the vascular networks spontaneously generated new capillary sprouts to increase the network's reach, much in the way blood vessels in the body naturally grow. The team then created gels containing primary liver cells to test whether their technique could improve their function.
When the researchers pumped nutrient-rich media through the gel's template-fashioned vascular system, the entrapped liver cells boosted their production of albumin and urea, natural components of blood and urine, respectively, which are important measures of liver-cell function and health. There was also clear evidence of increased cell survival around the perfused vascular channels.
And theoretical modeling of nutrient transport in these perfused gels showed a striking resemblance to observed cell-survival patterns, opening up the possibility of using live-cell data to refine computer models to better design vascular architectures.
Though these engineered tissues were not equivalent to a fully functioning liver, the researchers used cell densities that approached clinical relevance, suggesting that their printed vascular system could eventually be used to further research in lab-grown organs and organoids.
"The therapeutic window for human-liver therapy is estimated at one to 10 billion functional liver cells," Bhatia said. "With this work, we've brought engineered liver tissues orders of magnitude closer to that goal, but at tens of millions of liver cells per gel we've still got a ways to go.
"More work will be needed to learn how to directly connect these types of vascular networks to natural blood vessels while at the same time investigating fundamental interactions between the liver cells and the patterned vasculature. It's an exciting future ahead."
With promising indications that their vascular networks will be compatible with all types of cells and gels, the team believes their 3D printing method will be a scalable solution for a wide variety of cell- and tissue-based applications because all organ vasculature follows similar architectural patterns.
"Cell biologists like the idea of 3D printing to make vascularized tissues in principle, but they would need to have an expert in house and highly specialized equipment to even attempt it," Miller said. "That's no longer the case; we've made these sugar-based vascular templates stable enough to ship to labs around the world."
Beyond integrating well with the world of tissue engineering, the researchers' work epitomizes the philosophy that drives much of the open source 3D printing community.
"We launched this project from innovations rooted in RepRap and MakerBot technology and their supporting worldwide communities," Miller said. "A RepRap 3D printer is a tiny fraction of the cost of commercial 3D printers, and, more important, its open-source nature means you can freely modify it. Many of our additions to the project are already in the wild."
Several of the custom parts of the RepRap printer the researchers used to make the vascular templates were printed in plastic on another RepRap. Miller will teach a class on building and using these types of printers at a workshop this summer and will continue tinkering with his own designs.
"We want to redesign the printer from scratch and focus it entirely on cell biology, tissue engineering and regenerative medicine applications," Miller said.
###
University of Pennsylvania: http://www.upenn.edu/pennnews
Thanks to University of Pennsylvania for this article.
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Sharapova loses at Wimbledon, will drop from No. 1
Sabine Lisicki of Germany reacts winning against Maria Sharapova of Russia during a fourth round single match at the All England Lawn Tennis Championships at Wimbledon, England, Monday, July 2, 2012. (AP Photo/Sang Tan)
Sabine Lisicki of Germany reacts winning against Maria Sharapova of Russia during a fourth round single match at the All England Lawn Tennis Championships at Wimbledon, England, Monday, July 2, 2012. (AP Photo/Sang Tan)
Maria Sharapova of Russia, right, congratulates Sabine Lisicki of Germany after she won a fourth round singles match at the All England Lawn Tennis Championships at Wimbledon, England, Monday, July 2, 2012. (AP Photo/Sang Tan)
Maria Sharapova of Russia reacts during a fourth round singles match against Sabine Lisicki of Germany at the All England Lawn Tennis Championships at Wimbledon, England, Monday, July 2, 2012. (AP Photo/Sang Tan)
Serena Williams of the United States reacts after defeating Yaroslava Shvedova of Kazakhstan during a fourth round singles match at the All England Lawn Tennis Championships at Wimbledon, England, Monday, July 2, 2012. (AP Photo/Kirsty Wigglesworth)
Serena Williams of the United States prepares for a fourth round women's singles match against Yaroslava Shvedova of Kazakhstan at the All England Lawn Tennis Championships at Wimbledon, England, Monday, July 2, 2012. (AP Photo/Kirsty Wigglesworth)
WIMBLEDON, England (AP) ? All at once, there was a frenzy of activity at a wet and windy All England Club early Monday afternoon.
Top-seeded and 2004 Wimbledon champion Maria Sharapova, a big hitter in her own right, was overpowered in a 6-4, 6-3 loss to No. 15 Sabine Lisicki. Four-time title winner Serena Williams was locked in a three-set tussle against a wild-card entry from Kazakhstan who is ranked 65th but is responsible for the only perfect set in women's professional tennis. Defending champion Petra Kvitova was trying to come back after dropping her opening set.
Oh, and over on Centre Court, there was the not-so-insignificant matter of 16-time Grand Slam champion Roger Federer's medical timeout to get treatment for his aching back.
The start of Week 2 at Wimbledon has been dubbed "Manic Monday," because it's the only major tournament that schedules all 16 fourth-round singles matches on one day.
Sure lived up to that moniker this year, even if rain prevented five of the eight men's matches from finishing.
The most newsworthy result was the abrupt end of Sharapova's bid to become the first woman since Williams in 2002 to win the French Open and Wimbledon in the same year. Less than a month after completing a career Grand Slam in Paris to return to No. 1, Sharapova bowed out against someone she had beaten the three other times they met. She will be replaced atop the rankings next week.
"Nothing is easy. Certainly not a Wimbledon title," Sharapova said. "So I don't know if it's easier or tougher now than it was years ago, but I don't think it's ever easier."
Federer, seeking a seventh trophy at the grass-court Grand Slam, beat Xavier Malisse 7-6 (1), 6-1, 4-6, 6-3 to reach a 33rd consecutive major quarterfinal, adding to his record. After the seventh game, Federer got help from a trainer for his back. When he returned, his play didn't appear to suffer all that much, other than slower-than-usual serves. On the other hand, Federer capped the match with a 122 mph ace.
"Honestly, I'm not too worried. I've had bad backs over the years. I've been around. They go as quick as they came," he said. "But of course I have to keep an eye on it now."
Federer now faces No. 26 Mikhail Youzhny, a 6-3, 5-7, 6-4, 6-7 (5), 7-5 winner over Denis Istomin. Federer is 13-0 against Youzhny, who chose to look on the bright side, saying: "I have one more chance."
The only other man assured a spot in Wednesday's quarterfinals is No. 1 Novak Djokovic. The defending champion improved to 12-1 against Viktor Troicki, his doubles partner for Serbia at the upcoming London Olympics, by winning 6-3, 6-1, 6-3 under the Centre Court roof.
"Weather is always an obstacle here," Djokovic said.
Two men's matches never started, and three were suspended: No. 4 Andy Murray leads No. 16 Marin Cilic by a set and a break; No. 10 Mardy Fish took the first set against No. 5 Jo-Wilfried Tsonga and they're tied 1-all in the second; No. 31 Florian Mayer leads No. 18 Richard Gasquet 6-3, 2-1.
The women's quarterfinals are set for Tuesday: No. 6 Williams vs. No. 4 Kvitova, who came back to beat No. 24 Francesca Schiavone of Italy 4-6, 7-5, 6-1; Lisicki vs. No. 8 Angelique Kerber, who ended the soon-to-retire Kim Clijsters' last Wimbledon 6-1, 6-1; No. 2 Victoria Azarenka vs. Tamira Paszek; and No. 3 Agnieszka Radwanska vs. No. 17 Maria Kirilenko.
Azarenka, the Australian Open champion, has lost only 14 games so far. The most interesting aspect of her 6-1, 6-0 win over 2008 French Open champion Ana Ivanovic? The pigeon feathers that slowly floated down to the grass after a bird collided with the roof.
"Sometimes it can be annoying when somebody is chewing chips right when you're serving. Doesn't really matter; you just have to stay focused on your game. Whatever is going on around is going on around. It's out of your hands," Azarenka said. "But the feathers? It was fun."
Lisicki certainly had a grand ol' time against Sharapova, smiling all the while.
She used flat, powerful groundstrokes to neutralize Sharapova from the baseline. She also served bigger than Sharapova, reaching 118 mph and collecting six aces. A second-serve winner at 117 mph earned Lisicki's third match point, which she converted with a second-serve ace at 108 mph, then dropped to her knees and shook her fists while Dallas Mavericks star Dirk Nowitzki cheered from her Court 1 guest box. (Michael Jordan's Chicago Bulls running-mate Scottie Pippen was at Williams' match on Court 2.)
"That's my game, to serve well and be aggressive. That's what I did. I think it worked well," Lisicki said. "As soon as I got the break in the second set, I knew, 'I'm going to take it home.'"
Lisicki missed seven months in 2010 because of a left ankle injury ? she's described what she went through as having "to learn how to walk again" ? and dropped out of the top 200. After twisting that ankle in April, Lisicki withdrew from two tournaments and then lost her opening matches at four consecutive events, including the French Open.
But she clearly has taken a liking to the All England Club, having reached the semifinals last year, when she lost to Sharapova.
Despite their history, Sharapova referred to Lisicki as "the girl I played today," rather than by name. Sort of the way Williams' father talked about Yaroslava Shvedova, who gave the 13-time major champion all she could handle over the last two sets before losing 6-1, 2-6, 7-5.
"Whatever her name is, her feet were moving very well," Richard Williams said. "Serena's feet weren't moving."
"Looked like Serena's just not playing. She's not moving forward. Standing still. Getting caught on her back heels too much," he said. "Looked like if the girl took the ball early, she won the point."
In the third round, Shvedova won every single point ? 24 of 24 ? in the first set against French Open runner-up Sara Errani, the first "golden set" by a woman in the 44-year Open era.
When Williams began Monday's match by sailing her first groundstroke, a backhand, long to trail love-15, did that perfect set by Shvedova cross her mind?
"I was worried about it," Williams joked. "I just said, 'Serena, just get a point in this set and try to figure it out.' I definitely thought about it."
Quickly, the question became not whether Williams would win a point ? OK, everyone knew that answer beforehand ? but whether Shvedova would win a game. Call it a "Serena Set": She won 16 of 19 points in one stretch and went ahead 5-0.
But from 2-all in the second, Shvedova began hitting backhand winners at will, serving better and returning well, too, reeling off five games in a row. After the second set ended on a forehand into the net by Williams, she earned a warning from the chair umpire for racket abuse.
Williams already was pushed to a 9-7 third set in the third round, then trailed Shvedova 5-4 in the third. But with her father yelling encouragement from the stands, Williams took the final three games.
They played through drizzles that left Shvedova's prescription glasses tough to see through, so she removed them. And at 5-5, she double-faulted twice in a row to set up break point, then missed a backhand wide. But Shvedova insisted her mistakes had nothing to do with her vision.
"It's just I was a bit nervous," she said.
Plus, of course, that was Williams out there.
"In the right moments," Shvedova explained, "she did the right things."
That included a running, stretching cross-court backhand lob that Shvedova let drop behind her for a winner.
"I was surprised it went in. Maybe it was wind or something," Shvedova said. "Very weird."
Richard Williams' take?
"Actually," he said, "it was luck, to be honest with you."
His daughter acknowledged she "had no intention of hitting that shot. ... I thought I was going for a backhand down the line, and somehow it ended up being a cross court lob. That was not in the plans whatsoever."
She'll play Kvitova in a quarterfinal between the only past Wimbledon champions left in the women's draw, now that Sharapova is gone. Williams is 2-0 against Kvitova, both straight-set victories in 2010, at the Australian Open and Wimbledon.
"She's obviously a great grass-court player, as well as I am," Williams said. "I'll be ready."
___
Follow Howard Fendrich on Twitter at http://twitter.com/HowardFendrich
Associated Pressmarchmadness mike d antoni nba trade rumors 2012 ncaa tournament schedule laurent robinson dantoni gillian anderson
Sunday, 17 June 2012
Sale-Kershaw duel doesn't really materialize
Associated Press Sports
updated 1:31 a.m. ET June 16, 2012
LOS ANGELES (AP) - The anticipated duel between Clayton Kershaw and Chris Sale never materialized. Both aces folded midway through a seesaw game that went to the Los Angeles Dodgers because their relievers performed a little bit better than their counterparts on the Chicago White Sox.
James Loney scored the go-ahead run on a wild pitch by Matt Thornton in the eighth inning, and the Dodgers beat the White Sox 7-6 on Friday night in the opener of an interleague series between division leaders.
Alex Rios hit his second homer of the game in the top half of the eighth, but the Dodgers went in front again in the bottom half.
Loney started the winning rally with a one-out single against Thornton (2-4). Dee Gordon walked and Elian Herrera grounded into a fielder's choice, putting runners at the corners. Bobby Abreu batted for Ronald Belisario (2-0) and Gordon took off for second as Thornton's first pitch to Abreu bounced past A.J. Pierzynski.
"We weren't holding the guy on, so there was no need to rush the pitch," Pierzynski said. "He just made a bad pitch. It happens."
Belisario pitched 1 1-3 innings for the victory and Kenley Jansen worked a perfect ninth for his 11th save in 14 chances.
Kershaw was charged with five runs - four earned - and eight hits over six innings with seven strikeouts.
"Baseball goes in cycles and it has its ups and downs," Kershaw said. "I mean, this game's not easy. Just because you had a couple of good starts, this game will continue to humble you. So you've just got to keep battling and competing.
"They have some big-name guys over there. The lack of familiarity didn't really bother me too much, but it's definitely different that facing the same teams in the NL West over and over again. That's for sure."
Sale, trying to win his sixth straight start, took an AL-leading 2.05 ERA into his marquee matchup against Kershaw, the reigning NL Cy Young Award winner. But Chicago's 23-year-old left-hander didn't get out of the sixth inning as the Dodgers rallied against Sale and Jesse Crain for five runs, giving them a 6-5 lead.
"Usually when we've had Sale on the mound, we're in pretty good shape. But they battled and just beat us," slugger Adam Dunn said.
Ivan De Jesus hit for Kershaw during the big rally and singled home a run to trim Chicago's lead to 5-3 after an RBI double by Juan Uribe. Gordon came up after De Jesus and bunted a line drive that tipped off the glove of first baseman Paul Konerko. But second baseman Gordon Beckham, heading toward first to cover on the botched sacrifice, was right there to catch it.
At that point, rookie manager Robin Ventura replaced Sale with Crain, who gave up a tying two-run double by Herrera and an RBI single by Juan Rivera that gave the Dodgers their first lead. But Rios erased that advantage when he belted a leadoff drive in the eighth.
Sale was charged with five runs, seven hits and a season-high four walks in 5 2-3 innings after allowing no more than three runs in any of his 11 previous major league starts.
"You feel good with him on the mound and a 5-1 lead in the sixth inning with the way he's been throwing, but tonight he just didn't get it done," Pierzynski said. "He walked too many guys. He walked Jerry Hairston three times, he walked Dee Gordon twice, and a couple other guys. That just can't happen. We were behind in the count on every guy."
Dunn gave the White Sox a 2-0 lead in the first, driving an 0-2 pitch to right for his major league-leading 23rd homer and fourth of his career against Kershaw. The 12-year veteran has connected in each of his last five starts.
"Against a guy like Kershaw, if you can get early runs it's great," Dunn said. "He's obviously one of the best in the game, if not the best, so you try to be aggressive and try to get something you can hit because he's got so many good pitches. I fell behind 0-2, so I was just trying to put the ball in play and ran into one."
The Dodgers also scored in the first when Gordon walked and came all the way around on Herrera's double. Herrera advanced on Pierzynski's sixth passed ball of the season, but was stranded when A.J. Ellis grounded out.
The third inning began a string of three consecutive innings in which the White Sox scored one run. Konerko hit an RBI single, Alexei Ramirez scored on a throwing error by Gordon after he charged Orlando Hudson's infield hit to shortstop, and Rios added his seventh homer to make it 5-2.
NOTES: Dunn has homered seven times in 74 at-at-bats against lefties, compared to none last season in 94 at-bats. ... Sale, who spent his two previous big league seasons as a reliever, batted in a regular-season game for the first time and had two strikeouts along with a sacrifice bunt. ... This is the sixth interleague series between the Dodgers and White Sox, who have shared the Camelback Ranch spring training facility at in Glendale, Ariz., since 2009. ... Kershaw's only other regular-season start against the White Sox was on June 26, 2008, when he pitched four innings in a 2-0 loss to John Danks at Dodger Stadium.
? 2012 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
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CSN: There was a familiar scene inside the locker room at Wrigley Field Friday. Frustration oozed from both manager and players as a lack of offense led to yet another rough loss.
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Sunday, 3 June 2012
The Internet news? Blog Archive ? Get Rid Of Spam
Every day, both dmoestic and corporate users of the internet receive considerable amounts of spam e-mail. They are not only annoying, but sometimes you can miss an important e-mail or newsletter simply because you lose it among the great number of e-mails that flood out your Inbox. Often you?ll find that important people neglect to read your e-mail, because busy people like them hardly have the time and patience to browse through the huge quantities of spam mail they receive. One solution to this problem is a filter or a free spam blocker. Many companies have designed filters for their customers. Many e-mail servers, especially the renowned ones that have a reputation to protect, have their own free spam blocker. There are several types of programs that can help you stop spam, including: ? the ones that are offered when you create a new e-mail address. Every company that provides e-mail service has a spam filter, including those that offer free accounts like Hotmail, Yahoo!, Gmail and so forth. ? there are also standalone programs that go through your mail folders regularly and do their best to separate valid e-mail from spam and unwanted mail. The main disadvantage with these free spam blockers is the fact that, when they do their checks, they use quite a large percentage of your computer?s resources and sometimes also of your bandwidth. Before installing this kind of free spam blocker, you?ll need to decide if this is okay with you. ? other types of free spam blockers are the ones that work as plug-ins to other programs like e-mail clients. The disadvantage with this kind of approach is that you need to download all your mail anyway, before the plug-in can do its stuff. When you decide to use a filter, you must be sure that you update it or install new versions regularly, because marketing researchers working for spammres are continuously developing new ways of ?fooling? the filters. Filter makers must keep up by improving their software accordingly. A free spam blocker works by looking for trigger words or phrases inside the text of the e-mails, and categorizing e-mails on that basis. Nowadays, there are special programs being created that are designed to pass spam through free spam blockers by re-arranging words or using a different language style in the e-mails. This is an unfair marketing strategy, of course, but if you want to be protected against it, you must always have an up-to-date version of your free spam blocker program. Specialists recommend that you should review your needs and see what kind of filter suits you best. Each approach has its advantages and disadvantages. You must make up your mind whether you want to use the default filter on the e-mail server, or if you want to download all your mail before scanning them, or if you are willing to share your bandwidth with a standalone application. The best way is of course, if you can blend all the programs in one, but that?s not always practicable. Still, it is advisable that you should not remain satisfied with the free spam blocker that your e-mail server provides, because you will probably continue to receive unwanted mail in spite of it. Using a plugin in addition to server-side filters is viewed by many experts as the most effective way of getting rid of spam, considering the trivial effort it takes to set up.
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Saturday, 2 June 2012
Creative HanZpad hurdles FCC, will deliver ICS and quad-core goodness to China
Creative Labs might want to get some white gloves, because we recognized its fingerprints on the HanZPad, a Chinese tablet platform which just landed at the FCC. Using its own ZiiLABS division's ZMS-40 ICS optimized SoC (system on chip), the thinnish 7.95mm tab looks to have meaty specs with a quad-core ARM 1.5GHz processor, 1280 x 800 10-inch IPS display, 1GB RAM and microSD slot allowing up to 64GB of external storage. On top of Android 4.0 support, Creative will be developing its own OS for the device, which will be distributed through OEMs and its own channels. While currently tapped for the Chinese market, Creative's weighty US presence may suggest it'll eventually reach across the Pacific -- if it does, let's just hope it leaves the smudges behind.
Creative HanZpad hurdles FCC, will deliver ICS and quad-core goodness to China originally appeared on Engadget on Fri, 01 Jun 2012 03:38:00 EDT. Please see our terms for use of feeds.
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