text:
Universal LogicUpdated 10/12/2016
Neocortex® is a new form of artificial intelligence that uses sensor information to learn. Originally co-developed between NASA and Vanderbilt University, it is unlike any other technology. The software is independent of any hardware, allowing it be used for a host of applications from data analysis to robot and motor control. It uses sensor information to discover multi-dimension patterns in dynamic environments.
Neocortex recognizes complex objects and can identify them in random locations, increasing flexibility. By automatically handling a wide range of constantly changing parts, Neocortex reduces the need for manual changeovers or months of initial engineering trying to recognize thousands of SKUs for a traditional vision system. It provides the ability to reliably recognize a wide range of objects not possible only with 3D vision. Neocortex is able to move boxes it has never seen before, learning on the fly. Neocortex machine learning software is utilized with Spatial Vision Robotics vision guidance software for Universal applications such as Unlimited Random Depalletization, Random Bin Picking and Random Bag Moving.
Universal Robotics is an artificial intelligence software company that uses sensor input to enable machines to see, react, and learn with human-like flexibility. Universal integrates 3D sensing, machine learning, and robotics through a highly adaptable software platform, which works with any machine and any sensor. The platform consists of modules that are grouped into products: intelligence (Neocortex), 3D sensing (Spatial Vision), and machine control (Autonomy). These products integrate into complete applications or function independently for implementation by Universal, integrators or end users.
Model: U7000A
Associated Categories


text:
Talk:Angela Anaconda
From Wikiquote
- Do not delete this page anymore! AngelaAnacondaFan, November 27, 2008, 12:34 PM
- Also do not block Wikiquote anymore! AngelaAnacondaFan, November 27, 2008, 12:46 PM
- We want to be able to edit Angela Anaconda. AngelaAnacondaFan, November 27, 2008, 12:46 PM
- This page was a real mess of random quotes. I've cleaned it up and removed the unnecessary headings. Soph 18:50, 24 September 2010 (UTC)
- Please also remember the differences between
- 'your' and 'you're'
- 'there', 'their', 'they're'
- do not add episode headings for episodes with no quotes
- Full stops and Capital Letters. Apostrophe's.
- If you know which episodes the quotes under 'unidentified episodes' belong to, then please help sort them. Soph 19:12, 24 September 2010 (UTC)

subset: commoncrawl


text:
Search Results
Keywords: trolley tracks
Historical Items Showing 3 of 192 View All
Item 15867
Laying Trolley Tracks, Sanford
Contributed by: Sanford-Springvale Historical Society
Date: circa 1905
Location: Sanford
Media: Print from Glass Negatives
Item 28802
The Gateway at the Cape Casino, Cape Elizabeth, ca. 1912
Contributed by: Seashore Trolley Museum
Date: circa 1912
Location: Cape Elizabeth
Media: Postcard
Item 29140
Dock Square and Trolley Tracks, Kennebunkport, ca. 1900
Contributed by: Kennebunkport Historical Society
Date: circa 1900
Location: Kennebunkport
Media: photograph
Exhibits Showing 3 of 8 View All
Many different types of trolley cars -- for different weather, different uses, and different locations -- were in use in Maine between 1895-1940. The "field guide" explains what each type looked like and how it was used.
At the heyday of trolleys in Maine, many of the trolley companies developed recreational facilities along or at the end of trolley lines as one further way to encourage ridership. The parks often had walking paths, dance pavilions, and various other entertainments. Cutting-edge technology came together with a thirst for adventure and forever changed social dynamics in the process.
History in Motion: The Era of the Electric Railways
Street railways, whether horse-drawn or electric, required the building of trestles and tracks. The new form of transportation aided industry, workers, vacationers, and other travelers.
Sites Showing 3 of 6 View All
Scarborough: They Called It Owascoag
The history of a 350+-year-old city south of Portland, the Scarborough site was constructed by representatives from Scarborough Historical Society, Scarborough Middle School, and Scarborough Public Library. Exhibits include the marsh, transportation and roads, shipyards and shipwrecks, clamming and lobstering, famous residents, and education.
The history of a northern Maine community as told by an array of local institutions and organizations. Site contributors include University of Maine at Presque Isle, Presque Isle Historical Society, Mark and Emily Turner Memorial Library, Presque Isle Middle School. Some of the topics include historic buildings, potato farming, transportation and the Aroostook Valley Railroad.
Highlighting Historical Hampden
An introduction to Hampden history as presented by students from Reeds Brook Middle School, the Edythe L. Dyer Community Library, and Hampden Historical Society. Areas focused on include early settlement, expansion, Riverside Park, Hampden Academy, important residents, shipyards, the War of 1812, and more.


text:
Hello Guest Login Here or
Windows 7 USB / DVD Download Tool 18.104.22.168Downloading file: Windows7-USB-DVD-tool.exe
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A useful utility for backing up your Windows 7 image (ISO) installation file When you purchase Windows 7 from Microsoft Store, you have the option to download an ISO file or compressed files. The Windows 7 USB/DVD Download tool allows you to create a copy of your Windows 7 ISO file on a...more
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text:
Here I show how I'm attempting to convert a Boba Fett casting into a Magneto, X-men :First Class helmet.
I'm about halfway done.
Good luck
Very cool. This should be a great build to watch.
Cool work, but WHHHHYYYYYYY!!!!???
Wow this looks surprisingly doable. Great idea
Veeeeery, very smart starting with an existing helmet. Can't wait to see it complete, man.
I would think you could be forgiven seeing that you are doing an excellent tutorial on the use of bondo and refinishing. The work looks good.
Just don't forget the sweeping, outward flare at he lower edge.
I just saw this on the RPF, and i must admit like most on here I did cringe a little at the site of the fett helmet. But that is some superlative work you've done, and after seeing some of you other pieces this is no doubt going to be awesome
You may have to just do all of what you can see and then shelve the project until more photos or another trailer comes out to finish the back. That sucks if you wanted to get this done for a premiere or something, though.
You probably have all the reference photos available, but this is the only shot I could find of the back of the helmet.
I dont know if thats the same helmet as seen in the trailers as it looks like he's wearing the original style magneto costume, so whether the helmet changes I dont know, but its a start
Here's more progress. Added some to the helmet for the "flare" towards the bottom of the helmet.
Comparing the photos I may have to flaten the top of the helmet more, although I like what I have. We'll see.
Interesting project! Looks like you're making good progress. Seems like working in Bondo would be an agonizingly slow process, compared to what looks like it would be a fairly straightforward clay sculpt. What led you down this particular path?
Thanks for the background. Always interesting to learn how people approach a project.
Going to add a "crown" of bondo to rework the top of the helmet. looks a little small so i want to fill the shape back out, more round and flat on top rather than pointy. i took too much out i guess when i removed the pie shape piece from front to back.
More to come after the weekend, busy pulling some parts for another project.


text:
Youth Speaker Denise Winston
Inspiring. Engaging. Informative.
A leading financial authority, author, media personality and 25-year veteran of the banking industry, Denise is an expert on the new cable show Money Made Easy and a frequent contributor to numerous media outlets including ABC TV, FOX Business, Woman's Day and Martha Stewart Radio. Approachable and authentic, Denise teaches how to succeed in life and how to manage money from a personal perspective that kids relate to. Students leave with actionable advice to survive some of life's sticky situations and the often-harsh real world of finance.
Denise's talks are powerful and inspiring. Everyone in the audience comes away knowing they are important and that they are here to do something wonderful—something that will make a difference in their own life and the lives of others. Denise places high value on helping and being helped, and that we get more done by working together.
Educators and students praise Denise for her ability to be a genuine role model, to demonstrate how to turn a negative into a positive, to have people laughing one minute and deeply reflecting the next, and to deliver an eye-opening message that resonates.
Denise offers the following programs:
- Get What You Want: Use the power of your mind to control your future and achieve your goals. Learn how to harness the power of your mind, create energy, enhance your mood, deal with negative people, set goals and achieve your wildest dreams.
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- Getting a Job: Showcase your skills, get the interview, then ace it. Learn how to identify your talents, write a killer resume, get references, find potential jobs, land an interview and become a top job candidate, then give your future boss what he or she needs.
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- Leadership: Achieve your goals and impact people's lives. Learn how to lead from the inside out, and how to use your unique talents to help yourself and others succeed and make a difference.
Programs are scalable, can be customized and range from 45 minutes to full-day seminars.
Want to learn more? Contact Denise today.


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The job is not finished quite yet, but the service has been excellent and I plan to utilise this service ongoing! Eric turned up the next day as requested and was patient whilst we learnt what is needed to make a video. Great service.
I hired We PhotoBooth You for my wedding at the start of the year. At first I was not sure about photo booths as I have not used one since the old style enclosed booths but when I seen their booth I was amazed!It is an open air booth meaning it took up no space at all and lots ..
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Spittin Game
Seriously can we put some more adds up to slow it down even more? Im on a very fast connection and it takes forever to load, then when you think it loaded and you can navigate around, it starts loading something else and your stuck again. Please put up more ads and shit on this forum so I can sit and watch my dick shrink smaller before the forum loads.


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What's New? Research Subscription Blog About
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I like to think I'm a knowledgeable shopper and a keen cook. In other words, I can put a meal on the table that is not only delicious but is made from ingredients with a certain integrity to them. But I have to admit to being an overenthusiastic shopper, and worse, occasionally downright wasteful in the kitchen. I am not the sort to bake scones purely to use up the sour milk I have just found in the fridge and I have probably thrown away almost as much bread and salad leaves as I have eaten. My excitement over a baker's loaf fresh from the oven will last precisely until I have had my fill, then I am unlikely to visit it again until it is hard enough to be declared a lethal weapon. Salad must always be crisp and perky if it is to interest me, which inevitably means some of it finds its way to the compost heap. Shameful? Well yes, I suppose so.
A new book out this week, The New English Kitchen by Rose Prince (£18.99, Fourth Estate), is just what I need to get me to mend my ways.
I read the bread chapter first. Once the initial enthusiasm for a loaf has passed there is, of course, the toast option, with olive oil, salad leaves and soft cheese, or spread with real dripping from Sunday's roast. But Rose Prince goes further: 'Next day, put a slice of the now drying bread into a bowl and ladle over some vegetable broth, or make a toffee pudding or a fruit charlotte. By the end of the week anything left can be made into breadcrumbs. Eat them spiked with lemon zest beside roast poultry or game, mix them with garlic, herbs and olive oil for stuffing vegetables, or store them in the freezer for bread sauce. By now,' Rose says, 'I think it would be safe to say your loaf has earned its keep. You bought it for a sandwich and it has contributed to four meals.'
Of course, this is how it should be, and how in many homes it always was. But this is not how most people I know cook nowadays. Sure, they would like things to be that way, but in practice they still find a lettuce turned to slime in the salad drawer of the fridge, or valuable chicken bones left till they are dry and too elderly to make stock with. Making the most of a loaf, a chicken, a round of beef is not in anyway akin to what I call 'tight-fisted cooking', something in which the British are world leaders (you know, that mean little habit of saving a few pennies by swapping the butter for margarine). It is simply about a respect for the food itself and a delicious way to cut down our food bills. Not to mention the fuzzy feeling you will get when you produce your eighth meal from a brace of pheasants.
But a sound kitchen is about so much more than making sure you use the bones for a shimmering stock. (Not to mention a creamy risotto, a ham hock and bean soup, a game and celery soup, a dish of pommes boulangere. (I could go on.) It is about the whole picture from farm and ocean to plate. It is about which fish to buy and which fish not to; about knowing the precise difference between a battery egg, a barn egg and a free-range egg and the mark our supper may make on the environment. That deep fish pie I made last night, with its furrowed top of mashed potatoes and thick parsley sauce, was positively sumptuous, and all the better for being made with fish from a sustainable source.
If I am to be a 'good' cook, by which I also mean a thinking cook, then it must mean more than making stock, saving my Parmesan rinds for soup and recycling my organic milk cartons. It may mean sometimes having to rethink the way I shop as well. With The New English Kitchen I have a blueprint with which to go forward.
Poached chicken with leeks, tarragon and creamy stock
A recipe from The New English Kitchen. This is simmered chicken, but with minimal work. The sublime match between chicken and tarragon is shown off at its best in this dish - and it's especially lovely to eat in the colder months with bread fried in dripping or a buttery baked potato. The point here is that you use the whole bird, carcass and all; even better if you use the giblets to make your stock. Serves 4.
60g butter
1 chicken, jointed into 8 pieces
900ml chicken stock
3 leeks, cut into rounds
leaves from 4 sprigs of tarragon
250ml double cream
Melt the butter in a casserole dish over a medium-high heat, but do not let it burn. Add the chicken joints and brown them on both sides, then pour over the stock. Bring to the boil, skimming away any foam. Turn down to a simmer, cover and cook for about 45 minutes until the chicken is tender. Add the leeks, tarragon and cream, season and cook for a further 10 minutes.
Vegetable broth with basil and garlic oil
This is where I place a round of not-so-fresh bread, torn into spoonable pieces, in the bottom of my bowl before I pour on Rose's soup. What sounds so basic suddenly becomes a filling and fragrant meal made from things that would normally have been thrown away. A gem. I found some splendid celeriac roots at the market this week, so fresh and earthy as to be irresistible. I peeled them and grated them coarsely then steamed them with a little lemon juice before stirring into my second bowl of this soup. Serves 4.
1.75 litres chicken stock
2 courgettes, quartered lengthways and sliced into small pieces
4 tbsp peas
2 medium potatoes, boiled and cut into 1cm dice
other optional vegetables include turnips, fennel, chicory or cooked flageolet beans - all but the beans finely chopped
for the sauce:
4 tbsp olive oil
2 garlic cloves, crushed to a paste with a little salt
6 sprigs of basil, torn to bits
Bring the stock to the boil in a large saucepan and add all the vegetables. Bring back to the boil and simmer for 5 minutes, by which time the vegetables should be cooked. Taste and adjust the seasoning. Mix together all the sauce ingredients in a pestle and mortar, or give them a stir and mashing in a bowl with a wooden spoon. Give everyone a bowl of soup, dropping a tablespoon of sauce on top.


text:
It's a recurring theme: American students are falling behind other countries in math and science.
But students like West High's Delian Asparouhov and Cottonwood High's Katrina Wright are doing more than their part to bring up the national average.
The two students have won the Siemens Award for Advanced Placement. Both teens earned perfect scores (5 out of 5) on all of their AP math and science tests last year. Each year, the Siemens Foundation finds the boy and girl from each state who performed the best on these tests and gives them a $2,000 scholarship.
AP tests are given at the end of grueling courses, such as AP Biology, AP Calculus, AP Chemistry and AP Statistics. Simply earning a passing grade (3 out of 5) is difficult. Asparouhov and Wright aced every test they tried.
"We felt the need to attract more and more students into the math and science disciplines because we feel that those are the disciplines that are going to have the solutions for the global challenges that we have, such as clean energy, health care, clean water, the environment, and the efficiency of manufacturing in the United States," said Tom McCausland, chairman of the Siemens Foundation board.
This fall, Asparouhov will attend Massachusetts Institute of Technology (MIT), and Wright is still deciding between the University of Utah and Brigham Young University.
"I was really happy and told my parents about it," said Wright, who plays the piano and violin. "They were really proud of me."
Meanwhile, busy Asparouhov forgot to tell his mother he'd won the award for a few weeks. The Bulgarian-born teen was nonchalant about the Siemens Award, but not about being accepted to MIT.
"We heard a huge scream from downstairs," remembered Elena Asparouhova of the day in December her son learned his dream of attending MIT would come true.
Asparouhov chose MIT over his parents' alma mater, California Institute of Technology, because it has a varsity crew team. Rowing is a passion of his, along with building and programming robots.
"I'm not surprised; he's absolutely brilliant," said Erick Chen, a fellow West student, when he heard about his friend's award. "One of the great things about him is he is remarkably humble about his achievements. There are certain types of people who wear their AP scores stamped across their forehead, and he isn't one of them."
Both students plan to pursue careers in the math or science fields.
"These students are in the top hundredth of one percent of students in the country," McCausland said. "These are the best and brightest kids in math and science in the country."


text:
|Publication number
|Publication type
|Application number
|Publication date
|May 23, 2006
|Filing date
|Aug 15, 2002
|Priority date
|Jul 6, 2002
|Fee status
|Also published as
|Publication number
|Douglas G Evans, Jeffrey C Kelly, Todd M DeWitt
|Original Assignee
|Kensey Nash Corporation
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (12), Non-Patent Citations (5), Referenced by (28), Classifications (17), Legal Events (3)
|External Links: USPTO, USPTO Assignment, Espacenet
This application is a Continuation of U.S. patent application Ser. No. 10/190,249, filed on Jul. 6, 2002, entitled Resorbable Structure for Treating and Healing of Tissue Defects.
Tissue defects are sometimes repaired with porous scaffolds comprising biocompatable materials. The porous nature of the devices allows the inward migration of cells, followed by the in-growth of tissue, thereby repairing the defect. The pore structure must be controlled to ensure optimal inward cell migration (e.g., sized large enough to accommodate cells, and avoid altering the cell phenotype), from which the new tissue may form. Current devices do not adequately control pore geometry, size, and distribution, with processes that are economically attractive. Additionally, open porous networks facilitate cell migration throughout the implant, thereby speeding up regeneration. Also, mechanical properties of existing porous structures are less than desirable for applications where the implant is subjected to post implant stresses. The porous nature also minimizes the amount of foreign material placed into the patient.
Most processes for producing porous biomaterial implants utilize a leaching method wherein a leachable substance such as sodium chloride is mixed with a biomaterial such as polymethylmethacrylate (PMMA) and later removed with a solvent such as water. U.S. Pat. No. 4,199,864 (Ashman), U.S. Pat. No. 4,636,526, (Dorman et al), and U.S. Pat. No. 5,766,618 (Laurencin et al), describe such methods. Such leaching methods are time consuming and in many instances only a portion of the leachable substance is effectively removed from the implant.
Other processes for creating porous medical implants utilize a vacuum freezing operation as described in U.S. Pat. No. 6,306,424 (Vyakarnam, et al), U.S. Pat. No. 5,766,618 (Laurencin et al), and U.S. Pat. No. 5,133,755 (Brekke). These processes are not generally suited to mass production and often utilize non-biocompatable solvents.
A "plasticized melt-flow" process (PMF) has been developed, in an effort to increase the strength, and reduce costs, of molded polymeric parts. Such a process is described in U.S. Pat. No. 6,169,122 (Blizard et al) and U.S. Pat. No. 6,231,942 (Blizard et al) and by David Pierick and Kai Jacobsen, "Injection Molding Innovation: The Microcellular Foam Process," Plastics Engineering, May 2001, pp 46–51 (such disclosures being incorporated herein by reference). In general, such a process uses a gas (e.g., N2, or CO2) under high pressures to create a supercritical fluid (SCF). The SCF, when depressurized, liberates the gas, thereby creating a porous structure.
The pores in the PMF processes noted above are nucleated by nucleating agents which are added in the range of 2 to 7 percent. As a result the pores may be more homogeneously dispersed through the molded part, than pores seen in other processing methods known in the art. The Pierick-Jacobsen paper reports that the aim of this technology is reducing costs, through the reduction of polymer used and decreasing cycle time, i.e., nucleating agent takes the place of matrix polymer, thereby reducing the amount of polymer needed.
The process is proposed for use in various industrial components (e.g., car mirror housings, ink and Laserjet printer parts), no medical applications, procedures, or devices are disclosed.
A CESP process (Controlled Expansion of Saturated Polymers), however, has been contemplated for use in manufacturing implantable polymer structures by Pfannschmidt, et al, "Production of Drug-Releasing Resorbable Polymer Stents with Foam Structure", Medical Plastics Technology News, Fall 1999-Winter 1999–2000, pp 10–12. The focus of the paper is the use of CESP for the incorporation of "thermally sensitive additives." These additives are suggested to include proteins and growth factors. The devices proposed to deliver these additives are stents. No structural or load-bearing applications are disclosed. In fact, the focus of the invention is the low temperature processability of the invention, however, the resulting process is not readily mass producible.
The CESP may be useful for the delivery of those agents because of the low temperature employed in the CESP process; that is, as previously mentioned, the temperature is not raised to create flow, but rather the pressure is. Therefore, additives may be used that would not survive the temperature of traditional high-temperature molding techniques. However, the CESP process additionally does not adequately address the problem of satisfactory tissue ingrowth or regeneration.
The need for higher strengths in porous polymers has previously been recognized, as in U.S. Pat. No. 6,169,122 (Blizard, et al), where the process is controlled to minimize the cell (i.e., porosity) growth. The aim of the invention is to create homogeneously distributed pores, of a small size (i.e., preferably below 50 microns). To this end, nucleation aids (e.g., talc and titania) are added to the polymer, in an effort to nucleate a larger number of pores during the decompression step (as previously described). However, this paper does not contemplate the problem of satisfactory tissue ingrowth or regeneration, since it strives to create pores that may not be of suitable size to cause effective cellular differentiation and reproduction.
These approaches to utilizing PMF and CESP types of processes for creating porous polymers, for the repair of tissue, would fall short of what is needed in existing surgical procedures. Higher strengths are paramount for implants that may need to withstand any loading following implant; additionally, some implant products (e.g., screws) require continuing strength to withstand the procedural stress. However, proper cell migration into the implant structure, in most cases, require pores on the order of 100 to 250 microns. Therefore, decreasing the pore size below about 100 microns—while increasing strength—could actually prohibit proper cell ingress.
Additionally, talc or titania nucleation aids may not be suited for certain cellular environments, and may further deter cell ingress, or damage or alter normal cellular function and differentiation if such cells were to infiltrate the implant.
The PMF and CESP processes, as disclosed above, creates pores that typically do not communicate with each other. This isolation slows and potentially prevents the continued ingress of cells, through the entire implant cross section, which may delay tissue development, and/or restrict tissue development to the regions at or near the surface of the implant.
Additionally, the closed cell pores of the PMF process do not address the concerns of heterogeneous degradation that occur in massive biodegradable implants. Hydrolysis is not an erosion phenomenon for most biodegradable polymers, but is, instead, a bulk process with random hydrolytic scission of covalent ester bonds. The correlation of in vivo and in vitro rates of hydrolysis has led to the theory that degradation is not facilitated by enzymatic catalysis, or at least not during the initial loss of molecular weight. Hydrolysis is affected by many factors including crystallinity, molecular weight, polydispersity, sterilization process, geometry of the device, total surface area exposed to interstitial fluid, sight of implantation, etc. Although many functions affect biodegradation, hydrolysis has generally been identified to proceed in four main steps i.e., hydration, strength loss, structural integrity loss, and mass loss.
The closed cell pores of the PMF and CESP processes may exasperate problems associated with heterogeneous degradation by providing multiple isolated chambers separated by a thin membrane. These thin membranes may expedite the movement of body fluids deep into the implant where they may pool for a prolonged period of time isolated from interstitial turnover.
In addition, the pores produced by these, and similar, processes typically have uniform or smooth surfaces between the matrix juncture (similar to that of honeycomb structures). Even if these processes were able to yield pores with open architectures, the smooth walls would not be conducive to cell attachment.
Accordingly, there exists a need for homogenous, mass-producible, higher strength, resorbable implants with large pores. The pores may be modeled (i.e., the surfaces made rough or irregular) or intercommunicating and/or foster cell attachment. Embodiments of the current invention address these and other shortcomings in the prior art.
The present invention provides a resorbable porous structure for healing tissue defects comprising a porous polymer body produced from a process utilizing an SCF but without, in a preferred embodiment, any nucleating aids or fillers.
In yet another embodiment, the present invention relates to an improved porous implant wherein the pores of the implant present a modeling material or agent on their surfaces. This "second" material provides a textured or roughened face to the internal surfaces of pores. Additionally, this second material can be incorporated in sufficient quantity to, among other things, create a microporous network connecting interior closed cell pores with each other as well as the exterior of the device.
In yet another embodiment, the structure is reinforced with a strengthening agent, as will be discussed later.
Certain polymers are very thermally sensitive and extended residence time within melt processing equipment (e.g., PMF equipment) can lead to extensive molecular weight degradation. Other polymers have very narrow processing windows where on the high end of a narrow range the polymer burns and on the low end of the range the polymer does not flow effectively and high stress conditions are created in the final part. By using a gas or solvent to plasticize the polymer, processing temperatures, pressures and time can be reduced. For example, when processing resorbable polymers (e.g. polylactide, polyglycolide, polycaprolactone, etc.), this reduction in processing temperature, pressure and time can help to preserve the molecular weight of the final product. By using described processes for this invention, these polymers can be used for creating large low-stress mass-produced resorbable medical devices.
PMF and PSPC (Phase Separation Polymer Concentration) (as described later) processes may appear complex and varied but in actuality produce similar results. It is recognized that there exists other processes that are known in the art, which also produce analogous systems and results These alternate processes are incorporated herein, to the extent practicable.
In the PMF process, the nucleating agent, if any, can be mixed into a gas permeated plasticized polymer. The gas (e.g. air, oxygen, carbon dioxide, nitrogen, argon, or any inert gas, including combinations thereof) trapped within the polymer begins to expand as the pressure external to the polymer is reduced. As the gas expands it attempts to create uniformly dispersed homogeneous spherical pores. The growth of the pores is disrupted as the walls defining the pores thin to the point that the nucleating agent begins to protrude and therefore the nucleating agent may act as a "modeling agent". As the gas continues to expand the modeling agent particles begin to interfere with each other and/or the expanding pore walls, and force the pore to take on an irregular shape.
In the PSPC process, the modeling agent is dispersed within a polymer solvent solution. The temperature of the mixture is lowered until crystals form within the solution. As the crystals grow they force the polymer into a smaller and smaller area similar to the expanding gas in the PMF process. The growth of the crystals is disrupted as they come in contact with the modeling agent. As the crystals continue to grow they press the modeling agent particles in contact with each other and are thus forced to grow around the particles in an irregular fashion. After solidification vacuum or leaching, a chilled non-solvent removes the solvent crystals.
By varying the ratio of polymer to modeling agent in the PMF and PSPC processes, the porosity, pore surface texture and geometry of the matrix may be controlled; wherein matrix is polymer, molding agent and porosity combined. Low polymer constituent concentrations combined with longer processing times allows the growth of large pores, thereby affecting mechanical and physical properties. The rate at which the pores grow (via gas expansion or crystal growth, as appropriate) can determine where in the polymer mass the modeling agent is located. Slow growth of pores allows the modeling agent to migrate within the thinning polymer walls and remain covered or encapsulated (see
Examples and Subtypes of Bioresorbable Polymers for
Construction of the Device of the Current Invention:
Aliphatic polyesters
Types 1 to 20
Native fibrous
Reconstituted fibrous
Recombinant derived
Copolymers of glycolide
Copolymers of lactide
Glycolide/l-lactide copolymers (PGA/PLLA)
Glycolide/trimethylene carbonate copolymers (PGA/TMC)
Lactide/tetramethylglycolide copolymers
Lactide/trimethylene carbonate copolymers
Lactide/ε-caprolactone copolymers
Lactide/σ-valerolactone copolymers
L-lactide/dl-lactide copolymers
Methyl methacrylate-N-vinyl pyrrolidone copolymers
Modified proteins
PHBA/γ-hydroxyvalerate copolymers (PHBA/HVA)
PLA/polyethylene oxide copolymers
PLA-polyethylene oxide (PELA)
Poly (amino acids)
Poly (trimethylene carbonates)
Poly hydroxyalkanoate polymers (PHA)
Poly(alklyene oxalates)
Poly(butylene diglycolate)
Poly(hydroxy butyrate) (PHB)
Poly(n-vinyl pyrrolidone)
Poly(ortho esters)
Poly-dl-lactide (PDLLA)
Polyesters of oxalic acid
Polyglycolide (PGA)
Polylactides (PLA)
Poly-l-lactide (PLLA)
Poly-p-dioxanone (PDO)
Polyurethanes (PU)
Polyvinyl alcohol (PVA)
Poly-β-hydroxypropionate (PHPA)
Poly-β-hydroxybutyrate (PBA)
Poly-β-alkanoic acids
Poly-β-malic acid (PMLA)
Poly-ε-caprolactone (PCL)
Pseudo-Poly (Amino Acids)
Trimethylene carbonate (TMC)
Tyrosine based polymers
In certain embodiments, the nucleating agent (or modeling agent) may be left out of the processing mix to allow the pores to grow (e.g. since fewer pores are nucleated they may grow larger). Pores in the range of about 50–500 microns may be used in an implant, but may preferably be about 100–300 microns. It is realized that there may be a strength trade-off with this approach.
The modeling agent may also be composed of one or more materials that may have the ability to react with each other to create additional substances within the porosity of the invention. For example, Chitosan and sodium hyaluronate powders can be blended into the polymer and chemically linked to each other within the pores of the invention. This is accomplished by rapid expansion of the pores resulting in exposure of the two modeling agents after which the pores are flooded with a pH-adjusted fluid. The pH-adjusted fluid dissolves the modeling agents within the pores creating a polyelectrolytic system. Within this system chitosan and hylauronate become bound to each other and precipitate out of solution as an insoluble hydrogel.
The incorporation of high modulus strengthening components (e.g., polymers, ceramics or metallics) as the modeling agent will affect the strength and toughness of the resulting structure. The strengthening agent may be in various forms (e.g., particulate, fiber or whisker). The incorporation of these strengthening components improves the strength, such that the pore size may be increased to allow inward cell migration, while retaining or improving the mechanical properties (when compared with a small pore implant without a strengthening component). Additionally, the same modeling agent used to affect the physical properties of the implant can also affect its biologic properties. Hydroxyapatite would not only improve the strength of the implant, but also be capable of, for example, extracting endogenous growth factors from the host tissue bed while functioning as a microporous conduit facilitating movement of interstitial fluid throughout the isolated porosities of the device. Examples of materials useful as modeling agents are listed in Table 2.
Examples of Materials that may be Utilized as Modeling Agents of
the Current Invention:
Bone allograft or autograft
Bone Chips
Calcium Phosphate
Calcium Sulfate
Demineralized bone
Hydroxy apatite
Hydroxyethyl methacrylate
Hyaluronic Acid
Mesenchymal cells
Natural Polymers
Oxidized regenerated cellulose
Phosphate glasses
Polyethylene glycol
Polyvinyl alcohol
Platelets, blood cells
Steel (e.g. Stainless Steel)
Synthetic polymers
Tricalcium phosphate
The modeling agent can serve multiple purposes which may include but are not limited to:
The irregular pore surfaces formed by the modeling agent serves multiple purposes which may include but are not limited to:
Additional materials may also be used at the time of manufacture to control the process output (e.g. plastisizers, surfactants, dyes, etc.) For example, processing the polymer with stearic agents will cause the thinning of matrix between the pores, which is most easily penetrable, or rapidly resorbing, following implantation. This will result in a device with high strength, and interconnected pores, which will afford easier migration of cells through the implant.
In yet another embodiment, the polymer and modeling agent, as well as the pores, once formed, can be invested with drugs or other biologically active or therapeutic agents including cells and cellular components (together "therapy") for rapid or slow delivery, as will be discussed. Additionally, microspheres may be incorporated for an additional mode of therapy delivery, as will be discussed. The methods of therapy delivery contemplated by the various embodiments of the current invention include: delivery from the polymer constituent, delivery from the pores, delivery from the modeling agent, and/or delivery via microspheres, including any combination of the preceding modalities. These therapies may treat any underlying condition, which necessitated the implant or procedure, and/or the therapy may treat or support the ingrowing or regenerated tissue. Examples of materials that can be incorporated into and/or delivered by the implant are listed in Table 3.
Examples with Some Sub-types of Biological, Pharmaceutical, and
other Therapies that can be Incorporated into and/or Delivered via the
Device in Accordance with the Present Invention
Cellular Material Deliverable via this Invention
Adipose cells
Blood cells
Bone marrow
Cells with altered receptors or binding sites
Endothelial Cells
Epithelial cells
Genetically altered cells
Growth factors
Mesenchymal stem cells
Progenitor cells
Skeletal muscle cells
Smooth muscle cells
Stem cells
Some Sub-types of Biological. Pharmaceutical, and other
Adenovirus with or without genetic material
Angiogenic agents
Angiotensin Converting Enzyme Inhibitors (ACE inhibitors)
Angiotensin II antagonists
Anti-angiogenic agents
Anti-bacterial agents
Anti-growth factors
Anti-inflammatory agents
Anti-platelet agents
Anti-proliferation agents
Anti-rejection agents
Anti-restenosis agents
Anti-thrombogenic agents
GP IIb/IIIa inhibitors
Anti-virus drugs
Arteriogenesis agents
acidic fibroblast growth factor (aFGF)
basic fibroblast growth factor (bFGF)
Bone morphogenic proteins (BMP)
epidermal growth factor (EGF)
granulocyte-macrophage colony stimulating factor
hepatocyte growth factor (HGF)
Indian hedgehog (Inh)
insulin growth factor-1 (IGF-1)
interleukin-8 (IL-8)
platelet-derived endothelial cell growth factor (PD-ECGF)
platelet-derived growth factor (PDGF)
transforming growth factors alpha & beta
(TGF-.alpha., TGF-beta.)
tumor necrosis factor alpha (TNF-.alpha.)
vascular endothelial growth factor (VEGF)
vascular permeability factor (VPF)
Beta blocker
Blood clotting factor
Bone morphogenic proteins (BMP)
Calcium channel blockers
Stem cells
Bone Marrow
Blood cells
Fat Cells
Muscle Cells
Umbilical cord cells
Chemotherapeutic agents
Cholesterol reducers
Clopidegrel (e.g., plavix)
Collagen Inhibitors
Colony stimulating factors
Cytokines prostaglandins,
Genetic material
GP IIb/IIIa inhibitors
Granulocyte-macrophage colony stimulating factor (GM-CSF)
Growth factor antagonists or inhibitors
Growth factors
Autologous Growth Factors
B-cell Activating Factor (BAFF)
Bovine derived cytokines
Cartilage Derived Growth Factor (CDGF)
Endothelial Cell Growth Factor (ECGF)
Epidermal growth factor (EGF)
Fibroblast Growth Factors (FGF)
Hepatocyte growth factor (HGF)
Insulin-like Growth Factors (e.g. IGF-I)
Nerve growth factor (NGF)
Platelet Derived Growth Factor (PDGF)
Recombinant NGF (rhNGF)
Tissue necrosis factor (TNF)
Tissue derived cytokines
Transforming growth factors alpha (TGF-alpha)
Transforming growth factors beta (TGF-beta)
Vascular Endothelial Growth Factor (VEGF)
Vascular permeability factor (UPF)
Acidic fibroblast growth factor (aFGF)
Basic fibroblast growth factor (bFGF)
Epidermal growth factor (EGF)
Hepatocyte growth factor (HGF)
Insulin growth factor-1 (IGF-1)
Platelet-derived endothelial cell growth factor (PD-ECGF)
Tumor necrosis factor alpha (TNF-.alpha.)
Growth hormones
Heparin sulfate proteoglycan
HMC-CoA reductase inhibitors (statins)
Immunosuppressant agents
inflammatory mediator
lnterlukin-8 (IL-8)
Lipid lowering agents
Low-molecular weight heparin
Bone morphogenic proteins (BMPs)
Nitric oxide (NO)
Radioactive materials
Iodine - 125
Iodine - 131
Iridium - 192
Palladium 103
Secondary Messengers
Signal Transduction Factors
Signaling Proteins
Stem Cells
Thrombin inhibitor
Tyrosine kinase Inhibitors
The resulting embodiments of this invention will be useful in the improved repair and regeneration of various soft tissue (e.g. tendon, muscle, skin) and hard tissue (e.g. bone, cartilage) types. Furthermore, it is contemplated that organs or sections thereof (e.g., liver, a heart valve, etc., see Table 4) may also be re-grown or regenerated with implants incorporating the technology of this invention.
Examples of tissues and procedures potentially benefiting from
the present invention
Ankle reconstruction
Bone biopsy
Bone tissue harvest
Burn treatment
Bypass surgery
Cardiac catheterization
Compression fractures
Cosmetic Surgery
Elbow reconstruction
Foot reconstruction
Gall bladder
Hand reconstruction
Heart valve replacement
Hip reconstruction/replacement
Knee reconstruction/replacement
Long bone fixation
Maxillofacial reconstruction/repair
Ridge augmentation
Shoulder reconstruction
Spinal arthrodesis
Spinal fixation/fusion
Third molar extraction
Topical wound
Trauma repair
Wrist reconstruction
Suitable materials, and additives, for the polymer constituent of these various embodiments includes, but is not limited to, those listed in the above referenced tables. Various resorbable polymers are contemplated by this invention, but components or constituents may also be made of non-resorbable materials, as well. In this regard, In these various embodiments, as well as the balance of the specification and claims, the term "resorbable" is frequently used. There exists some discussion among those skilled in the art, as to the precise meaning and function of resorbable materials (e.g., polymers, ceramics), and how they differ from bioabsorbable, absorbable, bioresorbable, biodegradable, and bioerodable materials. The current disclosure contemplates all of these materials, modalities, or mechanisms, and considers them as equivalent with regard to the function of the current embodiments, even though these processes may be proved to differ significantly in practice, as they are similar in objective and result.
An ideal tissue repair/treatment/prosthetic device should possess various of the following properties: (1) it should be chemically biocompatable; (2) it should be partially if not completely resorbable so that the patient's own tissue ultimately replaces at least a portion of the device; (3) it should be porous to allow the infiltration of cells over time; (4) the porosity should provide it with a high surface area to mass ratio for cell attachment and delivery of therapeutics; (5) despite the porosity, it should provide a high degree of structural integrity in order to support, fixate, or treat surrounding tissues until the patient's own bone/tissue heals; (6) the device should have the ability to incorporate additives used to enhance the mechanical or biochemical performance of the device (e.g. strengthening agents, cells, drugs, biomolecules, other agents); and, (7) the device should be mass manufacturable to be able to provide the product at a reasonable price to the consumer. The various embodiments of the current invention address these properties.
The basic PMF process entails four general steps: 1) gas dissolution, 2) nucleation, 3) cell growth, and 4) shaping. During gas dissolution, a blowing agent or supercritical fluid (e.g., CO2 or N2) is injected into molten polymer (together the "chamber material"), in a pressurized process chamber. During nucleation, the gas, which is in solution within the polymer melt, comes out of solution to form a suspension of bubbles within the melt (i.e., acts as a "pore induction fluid"). This occurs as a result of a change in the conditions that affect the solubility of the gas within the polymer melt. For example, a rapid pressure drop or temperature change would affect gas solubility. In some instances, a nucleating agent such as talc is added to the chamber material to promote the formation of a nucleation site. As such, the processing conditions and the presence of a nucleating agent can affect, and therefore lead to control of, the cell growth. The shaping of the final part is controlled by the mold or by some type of final post processing (e.g. machining).
In a preferred embodiment, the improved process of the current invention entails the combining of a system for delivering controlled gas dispersion with a system for producing the porous component in its final form. The component may be produced by one of several methods traditionally used in the manufacture of plastic products. These include injection molding, extrusion, and blow molding.
The gas delivery unit provides a high pressure, accurately metered flow of gas that has reached a stage of Supercritical Flow (SCF). This gas in its SCF state is then delivered to the plastic process equipment at a point in the melt flow of the plastic material that has been determined to produce a final molded or extruded component with an optimized degree of porosity. The addition of a modeling material (as previously described), at this stage or earlier, may result in the formation of irregular pores with a textured surface.
In various of these embodiments, the optimization of this system includes the balancing of three conditions: 1. The gas blowing agent chosen may be introduced in amounts higher than conventionally used in foaming applications and must be completely dissolved in the polymer before pressure is lowered; 2. The blowing agent or SCF gas stays in solution in the melt flow by maintaining a consistent pressure profile; 3. There must be a high rate of change of solubility versus pressure.
The gas delivery system must introduce the proper amount of SCF gas into the melt flow in the plasticising unit of the injection molding or extrusion equipment to create the desired effect on the melt flow. This gas must be introduced at a pressure that is higher than pressure existing in the plasticising unit. In a preferred embodiment, the chamber material may be heated to improve flowablility or to tailor the resulting porosity. Heat may be supplied to the chamber material while it is under pressure in the chamber and/or while it is being expanded in the mold.
Both injection molding and extrusion or blow molding applications of the PMF system should require customization of a standard plasticizing unit to allow creation of a homogeneous and single-phase polymer melt solution, which, in a preferred embodiment, contains a modeling agent. Changes to tooling may be required to optimize production of specific components. In addition, the software that controls machine cycle functions of an injection molding or other processing system may need to be modified.
In yet another embodiment, the process includes subjecting the polymer and any modeling agent to solvent vapors under high pressure. The solvent vapors penetrate and plasticize the polymer without the addition of high heat. The polymer is then rapidly subjected to reduced pressure thereby boiling off the solvent vapors, expanding the polymer and leaving behind a porous structure.
Solvents with low boiling points are favorable in this process (e.g. acetone, tetrahydrofuran, etc.)
In yet another embodiment, the modeling agent is dispersed within a polymer solvent solution. The temperature of the mixture is lowered until crystals form within the solution. As the crystals grow they force the polymer into a smaller and smaller area similar to the expanding gas in the PMF process. The growth of the crystals is disrupted as they come in contact with the modeling agent. As the crystals continue to grow they press the modeling agent particles in contact with each other and are thus forced to grow around the particles in an irregular fashion. After solidification vacuum drying or leaching in a chilled non-solvent removes the solvent crystals.
In addition to catalyzing the formation of irregular shaped pores with a textured surface, a preferred embodiment uses the modeling agent as a strengthening component. The strengthening components are added to the matrix, thereby increasing strength and/or toughness. These strengthening components may be polymers, resorbable or non-resorbable, which may be suitable for primary matrix components themselves (but vary in a mechanical or physical property from the primary polymer); or the strengthening component may be non-polymeric (e.g., ceramic).
There are numerous ceramic systems that display both biocompatability and degradability. One application of devices made with the process of this invention is devices for repair of bone. In the body, the bone itself is the natural storehouse of minerals. The major mineral component of bone is hydroxyapatite, a form of calcium phosphate. Other calcium phosphate salts in bone include monotite, brushite, calcium pyrophosphate, tricalcium phosphate, octocalcium phosphate, and amorphous calcium phosphate. Additionally, bone contains calcium carbonates. Hydroxyapatites and tricalcium phosphates are the most widely studied of the calcium phosphates, which have calcium to phosphate ratios of between 1.5 and 1.67, respectively. Calcium phosphate, Ca10(PO4)6(OH)2, is known as a physiologically acceptable biomaterial which is useful as a hard tissue prosthetic. Another calcium mineral used as a bone replacement material is calcium sulfate. Each of these materials either alone or in combination with other materials would serve as suitable strengthening agents. In addition, it is recognized that other osteoinductive, osteoconductive, and inert materials may be suitable for the strengthening agent of the present invention.
Alternatively, strengthening agents may comprise fibers, whiskers, platelets or other oriented additions. These agents also may be resorbable, non-resorbable, or even non-polymeric in composition.
The methods of therapy delivery contemplated by the various embodiments of the current invention include: delivery from the polymer constituent, delivery from the pores, delivery from the modeling agent, delivery from a coating, and/or delivery via microspheres, including any combination of the preceding modalities.
Polymer constituent therapy delivery may be through various mechanisms, including but not limited to, therapy incorporated into the polymer constituent by physical entrapment or by conjugation of the therapy with the monomer or polymer.
Therapy delivery may come from the pores, as release from physical entrapment of the therapy from an enclosed pore, it may come from material adsorbed or loosely adhering to the surface of enclosed or interconnected pores, or it may stay suspended within the pores of the implant awaiting contact with cells entering the pores.
It is recognized that each of the delivery modes could result in different delivery rates. That is, therapy may evolve more rapidly from interconnected pores, than from isolated pores, which may in-turn release therapy faster than any therapy delivered by the polymer constituent (i.e., as it degrades).
In one embodiment the therapy is co-mingled with the various other constituents and components prior to the processing. This allows for some concentration of the therapy to remain in the polymer constituent, while some of the same therapy migrates or precipitates into the porous region of the matrix. An equilibrium phase diagram for the components and constituents would allow the tailoring of the concentration of therapy in each region (i.e., pore or polymer constituent), additionally, therapies with low solubility in either component will aid preferential placement of therapy. Therapy composition, PMF process pressure-temperature parameters, and time, among other variables, will affect the final location and concentration of the therapy.
Addition of a secondary therapy, or other active or inactive agent, may alter the solubility of a primary therapy in either region, thereby altering primary therapy placement.
Alternatively, a secondary therapy may be added because of its complementary therapeutic effect, or because of its preference to precipitate in an alternate region of the matrix (compared with the primary therapy). Any plurality of therapies are deliverable by these techniques.
The therapies may be of various states (i.e., solid, liquid, gas, plasma, etc.), prior to introduction, into the pore forming process; this may affect their ultimate solubility, and it is recognized that the therapy state in the finished matrix may not be the same as what was added.
In some instances it may be beneficial to utilize multiple gases with the polymer processing system. For example, each specific gas could be utilized to carry one or more therapies. The incorporation of the gas into the polymer solution could be customized to optimize the delivery of the therapy. Multiple gases could also be used to create a multi-phasic system of cell sizes and distribution within the final device.
The subject invention can also incorporate cellular additions. Cellular material may be delivered in combination with, or independent of drug delivery. The cellular material may be present on the inside of the implant, outside of the implant, or incorporated within the implant in a porous construct, or other such embodiment. The cellular material may be added to the implant immediately prior to insertion into the body of the living being or may be grown on the implant in the days or weeks prior to implantation so more mature cells are in place when the device is implanted. If the cells are seeded on the implant several days or weeks prior to implantation, the implant may be placed in an in-vitro setup that simulates the in-vivo environment (e.g., where blood or a blood substitute medium is circulated at appropriate pressure and temperature) to acclimate the cells to the host environment. The cell-seeded implant may be incubated in this in-vitro setup at physiologic conditions for several days prior to implantation within the body. Cell seeding techniques have been developed for a variety of cell types. Examples of cellular material that may be seeded on implant include those listed in Table 3.
It is also conceived that a source of cytokines or growth factors (e.g. platelet-rich plasma, bone marrow cells, etc.), whether synthetic, autologous or allograft in origination, can be delivered with the devices of this invention (e.g. incorporated into the implant or delivered via the delivery system). For example, it is known that one of the first growth factors to initiate the cascade leading to bone regeneration are platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-β). Each of these growth factors is derived from the degranulation of platelets at the wound, defect or trauma site. It is believed that increasing the presence of such platelets at the wound or trauma site can increase the rate of healing and proliferation needed to regenerate bone.
The application of platelet-rich plasma (PRP) or other autologous blood components is one way to deliver a highly concentrated dose of autologous platelets. PRP is easily prepared by extracting a small amount of the patient's blood and processing it, for example using gradient density centrifugation, to sequester and concentrate the patient's platelet derived growth factors.
Bone marrow may also be added to the present invention to aid in healing and repair.
It is further contemplated that gene therapy may be delivered via the various embodiments of this device. Gene therapies are currently of two primary types, and are both together hereinafter referred to as "gene therapy" or "engineered cells", however others are anticipated; the primary methodologies and basic understandings are described herein (see also table 3).
First, nucleic acids may be used to alter the metabolic functioning of cells, without altering the cell's genome. This technique does not alter the genomic expressions, but rather the cellular metabolic function or rate of expression (e.g., protein synthesis).
Second, gene expression within the host cell may be altered by the delivery of signal transudation pathway molecules.
In a preferred embodiment, mesenchymal stem cells are harvested from the patient, and infected with vectors; currently, preferred vectors include phages or viri (e.g., retrovirus or adenovirus). This preferred infection will result in a genetically engineered cell, which may be engineered to produce a growth factor (e.g., insulin like growth factor (IGF-1)) or a morphogen (e.g., bone morphogenic protein (BMP-7)), etc. (see also those listed in Table 3). Methods of infection as well as specific vectors are well known to those skilled in the art, and additional ones are anticipated. Following this procedure, the genetically engineered cells are loaded into the implant. Cytokines as described and used herein are considered to include growth factors.
Loading of the cells in this embodiment may be achieved prior to processing, during, or immediately following the implantation procedure. Loading may be achieved by various methods including, but not limited to, the injection of a solution containing said engineered cells into the implant, by combining said cells with said matrix components prior to fabrication, or following fabrication or implant.
The term "microsphere" is used herein to indicate a small additive that is about one to three orders of magnitude smaller (as an approximate relative size) than the implant. The term does not denote any particular shape, it is recognized that perfect spheres are not easily produced. In addition to true spheres, the present invention contemplates elongated spheres and irregularly shaped bodies. "Nanosphere" is used herein to denote particles, whether spherical or irregular, that are several orders of magnitude smaller than microspheres.
Microspheres can be made of a variety of materials such as polymers, silicone and metals. Biodegradable polymers are ideal for use in creating microspheres for use in these embodiments (e.g., see those listed in Table 1). The release of agents from bioresorbable microparticles is dependent upon diffusion through the microsphere polymer, polymer degradation and the microsphere structure. Although most any biocompatible polymer could be adapted for this invention, the preferred material would exhibit in vivo degradation. It is well known that there can be different mechanisms involved in implant degradation like hydrolysis, enzyme-mediated degradation and bulk or surface erosion. These mechanisms can alone or combined influence the host response by determining the amount and character of the degradation product that is released from the implant. The most predominant mechanism of in vivo degradation of synthetic biomedical polymers like polyesters and polyamides is generally considered to be hydrolysis, resulting in ester bond scission and chain disruption. In the extracellular fluids of the living tissue, the accessibility of water to the hydrolysable chemical bonds makes hydrophilic polymers (i.e. polymers that take up significant amounts of water) susceptible to hydrolytic cleavage or bulk erosion. Several variables can influence the mechanism and kinetics of polymer degradation. Material properties like crystallinity, molecular weight, additives, polymer surface morphology, and environmental conditions. As such, to the extent that each of these characteristics can be adjusted or modified, the performance of this invention can be altered.
In a homogeneous embodiment (i.e., monolithic or composite of uniform heterogeneity) of a therapy delivering implant material, the device provides continuous release of the therapy over all or some of the degradation period of the device. In an embodiment incorporating microspheres, the therapy is released at a preferential rate independent of the rate of degradation of the matrix resorption or degradation. In certain applications it may also be necessary to provide a burst release or a delayed release of the active agent. The device may also be designed to deliver more than one agent at differing intervals and dosages, this time-staged delivery also allows for a dwell of non-delivery (i.e., a portion not containing any therapy), thereby allowing alternating delivery of non-compatible therapies. Delivery rates may be affected by the amount of therapeutic material, relative to the amount of resorbing structure, or the rate of the resorption of the structure.
Time-staged delivery may be accomplished via microspheres, in a number of different ways. The concentration of therapeutic agent may vary radially, that is, there may be areas with less agent, or there may be areas with no agent. Additionally, the agent could be varied radially, such that one therapy is delivered prior to a second therapy—this would allow the delivery of non-compatible agents, with the same type of sphere, during the same implant procedure. The spheres could also vary in composition among the spheres, that is, some portion of the sphere population could contain one agent, while the balance may contain one or more alternate agents. These differing spheres may have different delivery rates. Finally, as in the preceding example, there could be different delivery rates, but the agent could be the same, thereby allowing a burst dose followed by a slower maintained dose.
Thus since the invention disclosed herein may be embodied in other specific forms without departing from the spirit or general characteristics thereof, some of which forms have been indicated, the embodiments described herein are to be considered in all respects illustrative and not restrictive. The scope of the invention is to be indicated by the appended claims, rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.
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|Citing Patent
|Filing date
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|Massachusetts Institute Of Technology
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|Osteochondral repair using plug fashioned from whole distal femur or condyle formed of hydrogel composition
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|Curaseal Inc.
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|Curaseal Inc.
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|Curaseal Inc.
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|Jul 17, 2012
|Boston Scientific Scimed, Inc.
|Deforming surface of drug eluting coating to alter drug release profile of a medical device
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|Collagen Matrix, Inc.
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|Curaseal Inc.
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|Evonik Corporation
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|Evonik Corporation
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|Curaseal Inc.
|Fistula treatment devices and methods
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|Dec 15, 2015
|Curaseal Inc.
|Fistula treatment devices and related methods
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|Feb 19, 2004
|Reinhold Schmieding
|Osteochondral repair using plug fashioned from whole distal femur or condyle formed of hydrogel composition
|Aug 10, 2004
|Feb 16, 2006
|Stenzel Eric B
|Coated medical device having an increased coating surface area
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|Aug 3, 2006
|Timm Mary J
|Deforming surface of drug eluting coating to alter drug release profile of a medical device
|Oct 14, 2005
|Oct 12, 2006
|The Cleveland Clinic Foundation
|Device for tissue engineering
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|Serdy James G
|Manufacturing process, such as three dimensional printing, including binding of water-soluble material followed by softening and flowing and forming films of organic-solvent-soluble material
|Apr 25, 2007
|Nov 1, 2007
|Mei Wei
|Calcium phosphate polymer composite and method
|May 12, 2005
|Feb 7, 2008
|Massachusetts Institute Of Technology
|Manufacturing Process, Such as Three-Dimensional Printing, Including Solvent Vapor Filming and the Like
|Jan 9, 2007
|Jul 10, 2008
|Cardia, Inc.
|Bioabsorbable occlusion device
|Feb 28, 2008
|Aug 28, 2008
|Roeder Ryan K
|Porous composite biomaterials and related methods
|Apr 1, 2009
|Mar 25, 2010
|Akshay Mavani
|Implantable fistula closure device
|Dec 30, 2008
|Jul 1, 2010
|Collagen Matrix, Inc.
|Biopolymeric membrane for wound protection and repair
|Sep 28, 2009
|Sep 30, 2010
|Akshay Mavani
|Inflatable device for enteric fistula treatment
|Sep 28, 2009
|Sep 30, 2010
|Akshay Mavani
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|Pharmaceutical composition comprising cd34+ cells
|U.S. Classification
|521/82, 521/97, 424/426, 521/182
|International Classification
|Cooperative Classification
|European Classification
|Feb 6, 2003
Owner name: KENSEY NASH CORPORATION, PENNSYLVANIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:EVANS, DOUGLAS G.;KELLY, JEFFREY C.;DEWITT, TODD M.;REEL/FRAME:013728/0527;SIGNING DATES FROM 20030121 TO 20030123
|Aug 14, 2009
|Fee payment
Year of fee payment: 4
|Oct 23, 2013
|Fee payment
Year of fee payment: 8


text:
Separate names with a comma.
Discussion in 'TiVo Help Center' started by ccwf, Aug 24, 2003.
Does the code shown for the M55CB not work? Did you try the Sony codes recommended by the TiVo box?
DCT700 Help with Phillips Tivo DVR.
Cannot get this new cable box w/out serial port to work using IR blaster. Tried Motorola and GI codes. Any suggestions?????
I seem to be stuck in TiVo/Dish hell! Hoping I can get some pointers here.
I read quite a bit in this thread and a few others over the past three weeks, seeking to be informed before ordering our Dish Satellite service. I wanted to be sure it would work with our Humax DTR-800. We've been using it for 1.5 years with Broadcast TV, and the signal just isn't good enough, so decided to go with Satellite -- which was installed this morning.
The satellite signal worked fine when delivered directly to the TV. Dish installer guys completely unplugged my TiVo.... argh.
Got it all re-hooked this evening, followed instructions in the manual meticulously, including the IR blasters. Then stepped TiVo through the Guided Setup and... nothing!
After going through several screens, entering Zipcode, choosing which Sat. service, etc., there is a screen where TiVo reports if it's receiving a video signal -- and it says it is, but the next screen asks if I see TV in the background, and I do not. I get stuck there.
Overlooked mentioning that TiVo setup has required about three reboots this evening, each one requiring a login to the service and downloading updates (via home network, so at least that's good and fast)... so the silly thing ought be as updated as possible!
Oh, Dish receiver is the 2-tuner model 322.
So, if anyone can give me any clues, I'd be most appreciative!
John Fischer, Portland, Oregon
You sure you have the TiVo connected to the TV1 output and not the TV2 output? The IR controller will only work on the TV1 out.
I've seen it too with my 240.
In a different thread last evening, I posted this problem:
This morning, I called Humax for help with this. The solution was ridiculously simple:
The Technician had me to go Video Hookup, and switch from the A/V feed from which the Satellite signal was coming, to the RF feed on which I have a set of rabbit ears for back up on Broadcast TV. Then he had me switch back to the A/V feed -- and bingo -- the Sat. signal was there!
Better still, it was tuned to Comedy Central and the Cobert Report was the first thing I got to TiVo with my new Dish setup!
Crazy that it has been this awkward to get the thing going... but from other notes I've read, I'm learning that the SatCos are working hard to squeeze TiVo out of the market. Sure hope they can hang on!
I am grateful for this helpful community. (I do wish, however, that the index was easier to use and find which threads to use when newbies are seeking help!)
John Fischer, Portland, Oregon
Yes i tried all codes that im aware of to use this cable box
Can anyone tell me how to get my TiVo to work with a DirecTv H20 receiver. Any help would be great.
I am also trying to set up Directv's HD H20 model to my series2 Tivo. Anyone figure this one out yet?
Am I understanding this correctly? If I change my Tivo to use code 10074 with my D10 receiver I'll no longer get the problematic screen saver that messes up recording? How does this work?.
I would also like to know how to get the H20 to work with my series2.
I see no mention of the Motorola DCT 700 in the list. Becoming quite commonplace now. Comcast is deploying these as the standard SD STB in Northern California, and presumably elsewhere if they have the analog channels simulcast on digital, since the box is digital only. Very fast, recent, but not having good luck with 3-digit channel changes as yet.
From the thread:
it seems like you might want to try 00093-C IR code, but 10006 10019 10032
10042 and 10046 might also work. 10046-B might specifically work.
Haven't tried these yet. Will report back.
Born2Shop, Asshat5000, LoneStar1981;
The IR sensor for the H20 is extremely recessed. You will need to either bend your emitters down to obtain a good angle or try to get a stick-on IR emitter that attached directly to the window.
gconnery, our experience is that DCT700 is capable of using the same IR codes as any of the other DCT-series boxes. I recommend the higher numbered codes (10042, 10046) as they are usually more reliable than 00093. I do not have an exact location for the sensor on this model, but am told it should be located somewhere in the right third of the strip across the middle of the faceplate. Hope this helps.
I have 3 hd 10-250 hi-def dtv tivo's. I installed Fios which is fiber optic high speed internet service and that includes all phones lines to be digital.
The hd 10 250 phone call that tivo makes to upgrade service or what ever else they do will not work with the digital phone line.
Verizon which provides the service and is supposedly trying to correct this problem. Has any else encountered this problem and how was it solved?
This is really a question that does not fit into this IR control thread and should be posted as a new subject.
What I found on my H20 I had to have the 2 L shape IR on the right side of the round manual tuner dial on the center of the unit which there is no reason for this to work unless the receiver is located in this area. Mount them just to the right of the dial by the first button about an inch out. Mine would not work over the sensor on the front of the unit but way to the right of it, shooting the signal no where near it but it does work. took me a few days of moving the sensors around. Does not make sense but it works. I have the Series2 and it works.
MRELK2, you are a god!!!! I was going insane. You're right, it doesn't make any sense for the sensors to be placed way out on the right. But It works! Thanks again!!
Does anyone know if TiVo's 7.3 software release did in fact resolve the serial control problems caused by the 7.2 release related to the following satellite/HD receivers: Hughes HTL-HD, LG LSS-3200A, and Sony SAT-HD300?
I want to buy a satellite/HD receiver (for OTA HD reception use only) that I can control via serial port with my Series 2 ST TiVo - would appreciate any known solutions for this capability.
Ray (new member)
Welcome to the forum. This issue has been solved for some time.
Here are the instructions our agents give out:
To get serial to work in 7.2.1 and higher, go thru serial tests (first 2 will fail) then choose "Manually select serial control", then choose "APG-2".
If that does not work, have cust press red reset button near receiver's card.
Thanks, I really did try to look through all the postings before asking for help...must have missed it.
Great site - appreciate all the helpful information.


text:
Patricia Starbird, M.S., LPC/MHSP, EMDRIA Certified
Licensed Professional Counselor
Piney Flats, Tennessee 37686
Eating disorders are not about food. They are about control. As a child, we don't have much control and sometimes we are placed in situations where we are helpless to prevent abuse, neglect, and mistreatment. Just as the alcoholic drinks to "numb out" to their emotional pain, the young woman with an eating disorder will soothe herself with food before purging, or restrict food to combat the painful feeling of helplessness. Eating disorders are treatable. You must work with a therapist who has expertise in working with trauma. Such a therapist will work gently with you, at your own pace, and in a way that will assist you in healing the pain that is driving the eating disorder.
Leslie McKenna, M.S., L.P.C.
Licensed Professional Counselor
254 9th Ave Dr. NE, Hickory, North Carolina 28601
I have been working with women who have been suffering from eating disorders, sub clinical eating issues, and body shame issues since the early 1990's when I began my career at an inpatient eating disorder / substance abuse unit in Atlanta. My approach to eating disorders and body issues is influenced by the precepts of Acceptance Commitment Therapy. I work with women in cultivating a relationship of loving kindness with the "skin they're in", regardless of weight, age or shape. Clients learn that changes in eating patterns or weight no longer need to be inspired by culturally conditioned shaming which the diet industry and media promotes
Stephen Ellis, Ph.D
Licensed Christian Counselor
109 Leader Dr., Piedmont, South Carolina 29673
Eating disorders cover a wide range of behavior. This could be from simply eating too much to the more complex conditions of anorexia or bulimia. We have a special compassion for and an expertise in helping people that are struggling with eating disorders. Treatment plans include discipline strategies to change our thinking process about eating which results in a change of behavior. We also work with people who have experienced some type of emotional trauma which is usually a root cause of the more serious eating disorders. We work to find that root cause and not just deal with the symptoms of a condition.


text:
The next installment in the Spider-Man movie franchise, The Amazing Spider-Man 2, stars funny man (turned electrified super villain, Electro) Jamie Foxx. SplashNewsOnline posted a gallery of pics for the movie set this past Sunday (April 28). New York City's favorite web slinger has his work cut out for him when he goes head to head with his new big screen baddie on May 2, 2014.
Writer/Director For 'The Avengers 2′ Hints at Quicksilver and Scarlet Witch
We may have gotten a hint at the two new Marvel characters that will appear in "The Avengers 2."Click here to read more
Check out these two pics (which were posted a few weeks ago) of Jamie Foxx as Electro, courtesy of Comic Book Movie:
And lastly, this video may provide a sneak peek at the appearance of Rhino in the film as one of Spider-Man's second antagonist:
[poll id="81″]
WATCH: 1st Official Trailer for 'Thor: The Dark World'
Thor and Loki are working together again? This has to be good!Click here to read more


text:
Prince William had a case of royal pre-wedding jitters the night before the Royal Wedding.
In an upcoming interview with Alan Titchmarsh in the documentary, "Elizabeth: Queen, Wife, Mother," for Britain's ITV1, William opens up about the wedding that had the world watching.
PLAY IT NOW: Access Hollywood Live: Psychic Char Margolis Makes Projections For Celebrity Couples In 2012
"I hadn't slept at all that night because obviously all the crowds were on The Mall," he said in the documentary, which airs in the U.K. on June 1. "They were singing and cheering all night long. So, the excitement of that, the nervousness of me, and everyone singing meant I slept for about half an hour, I think."
The Prince admitted that his traditional wedding garb also made him nervous.
VIEW THE PHOTOS: From Regular To Royal: Kate Middleton
"The hardest thing was trying to walk down the stairs with my spurs on, sideways. I had visions of myself and my brother colliding and crashing down the stairs," he explained. "It was good fun, it was really good fun."
And when it came time to figuring out who to invite to such a massive event, Prince William said that the Queen was very helpful when it came to making the tough guest list decisions.
"There was very much a subdued moment when I was handed a list with 777 names on it - not one person I knew or Catherine knew," he recalled. "I went to [Queen Elizabeth] and said, 'Listen, I've got this list, not one person I know - what do I do?' And she went, 'Get rid of it. Start from your friends and then we'll add those we need to in due course. It's your day.'"
VIEW THE PHOTOS: Sexy Royal Sister Pippa Middleton
The 29-year-old future King says he's grown very close to his grandmother.
"We're definitely a lot closer than we used to be. I think being a small boy it's very daunting seeing the Queen around and not really quite knowing what to talk about or what to ask her," he explained. "I think over the years, that's got a lot better. I've grown up - hopefully - a little bit and tried to understand a bit more about her role and my own role."
VIEW THE PHOTOS: The Royal Bachelor: Prince Harry
As for the day when he'll take the throne, Prince William said he looks to those who've done it before him.
"There's not much wiggle room left for me to try and find my own path," he said. "It's just a matter of learning what's gone before me."
Copyright 2012 by NBC Universal, Inc. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


text: Merlin star Colin Morgan in Quirke - see the pictures The Northern Irish actor is back on our screens this Sunday playing Jimmy Minor opposite Gabriel Byrne's crime-solving pathologist Comments Written By Susanna Lazarus 3:16 PM, 05 June 2014 It's all gone a bit quiet for fans of Colin Morgan these last few months. The former Merlin star has taken time off from our screens in the past year, appearing in acclaimed stage plays of The Tempest and Mojo. Now he's back, guest starring opposite Gabriel Byrne in BBC1's Dublin-based drama Quirke before joining the cast of BBC2's The Fall later this year. Quirke sees Morgan playing a character named Jimmy Minor in Elegy, the third and final instalment based on the books by Benjamin Black (the pseudonym of award-winning author John Banville). And ahead of Morgan's long-awaited return to telly, we've got a batch of photos featuring the man himself... Quirke conclues on Sunday at 9:00pm on BBC1 Like this? Share it. Facebook Twitter Google Tumblr Pinterest Blogger Reddit VKontakt Print Email


text:
Archives.com is owned and operated by Inflection LLC, a Silicon Valley-based technology company.
Since Archives.com's launch in January 2010 (before that, the site was called Genealogy Archives), the site has grown to more than 380,000 paying subscribers who pay approximately $39.95 a year. Archives.com offers access to more than 2.1 billion historical records, including birth records, obituaries, immigration and passenger lists, historical newspapers, and US and UK censuses.
Inflection secured the contract with the National Archives to design and host the archives' website for the 1940 census records, released April 2. Archives.com also is a partner in the 1940 Census Community project, which has FamilySearch volunteers indexing the 1940 census. Ancestry.com is using a paid contractor to create its own 1940 census index. I'm curious to see what happens with this.
From Ancestry.com's press release: "This transaction will enable Ancestry.com to add a differentiated service targeted to a complementary segment of the growing family history category. In addition, Ancestry.com will welcome a team of talented engineers, digital marketers, and family history innovators into the Ancestry.com fold and also gain access to a proprietary technology platform that has supported Archives.com's rapid growth."
Upon completion of the transaction, which is subject to customary closing conditions, including expiration of the HSR waiting period, Ancestry.com will continue to operate Archives.com separately retaining its brand and website. Many Inflection employees are expected to join the Ancestry.com team.
We'll bring you more on this story as it develops.
You can watch the episode online at PBS.org.
Though not related, the two had a lot in common: Both were expectig baby No. 2 at the time of filming, both have parents in the film industry, both have Eastern European Jewish roots on one side of the family, and both also have ancestors in America before the Revolutionary War.
Gates' team could trace the Jewish roots only to the third-great-grandparent generation, but for each actor's other branches, Gates unrolled an enviably long family tree with many generations. (See closeups on the Genea-Musings blog.)
Gyllenhaal learned how her family really got its last name. The story was that a Swedish ancestor created a beautiful book about butterflies and the king rewarded him with a wonderful home known as "Golden Hall." What really happened was that an ancestor took the name after being knighted during the Thirty Years' War.
But like many family stories, there was a grain of truth. Another relative had amassed a collection of beetles that later became world-renowned.
Each star also took a DNA test, and Gates prompted them to compare the roles of nature versus nurture in making up their being. My favorite question of the night was when he asked Downey "Do you think that what happened in your family tree between 1300 and 1965 [the year of Downey's birth] has shaped who you are?"
I do believe that our ancestors' successes and struggles affect the next generation, that each of us can't help but carry these experiences inside us. Genealogy is partly a way of figuring out what's in there.
BTW, in the July/August 2012 Family Tree Magazine, we'll have Gates' answers to five of our burning questions about his genealogy work.
Here's what Paula sent:
Well, now I'm getting really curious! The Minnesota Genealogy Crash Course webinar with Paula Stuart-Warren is next Wednesday, April 25, at 8 p.m. (now available On Demand!)
Find out more about the Minnesota Genealogy Crash Course here.
The parish register ledger books document Lutheran congregations throughout the United States from 1793 to 1940.
The records will become available at Archives.com later this year. I'm crossing my fingers it'll be in time for our guide to genealogy research in Lutheran records, which will be in the July/August 2012 Family Tree Magazine.
The guide is part of our new religious records series, which so far has covered Catholic (in the March/April 2012 Family Tree Magazine) and Jewish (in the May/June 2012 Family Tree Magazine) genealogy research.
See the full announcement about Lutheran records on Archives.com here.
The name index for the state of Delaware is now completed and available to researchers. Search Delaware here.
You can use the map at FamilySearch's 1940 census site to see the indexing progress of the 1940 Census Community Project. The darker the state, the more records volunteers have indexed. The completed indexes will become searchable free on FamilySearch, as well as its commercial partners Archives.com and FindMyPast.com.
The name index for the state of Delaware is now completed and available to researchers. Search Delaware here.
You can use the map at FamilySearch's 1940 census site to see the indexing progress of the 1940 Census Community Project. The darker the state, the more records volunteers have indexed. The completed indexes will become searchable free on FamilySearch, as well as its commercial partners Archives.com and FindMyPast.com.
The 1940 census record images also are available on FamilyLink.com, which MyHeritage purchased last year. You'll need to register for a free account on the site (if you don't already have an account there) to view the records.
I did learn a few things about courthouse research, though. If that's what's on your genealogy to-do list, these tips might help:
1. Ask a local. Cleveland genealogist and Family Tree University instructor Diana Crisman Smith gave me the lowdown on the Cuyahoga County courthouse, parking and other details. If you don't know someone knowledgeable about the place you're headed, see if the local genealogical society has an online message board.
2. Have backup parking plans. The parking garage was full, so I drove around downtown and finally snagged the last space in a surface lot. Smaller towns might not have the same issues.
3. Be as prepared as possible. The Cuyahoga County probate court has an online docket you can search to find the case file numbers you need.
Other ways to be prepared: Call ahead and make sure there isn't a furlough day or special holiday on the day you plan to go. See if there are any restrictions on what you can bring (such as pens or backpacks). Bring cash for parking, copy fees and other expenses.
3. Don't be afraid to ask. I'm sure things work differently in every courthouse, but there was a procedure here. And there was no hand-holding, so I had to ask. I was told to write the case number on a request card for a clerk to retrieve the file. But for my relatively recent probate files (1980s and 90s), I was to use the computers to get microfilm numbers, then pull the film.
I thought all the microfilm readers were equally bad, but I should have asked about that too—a clerk walked by and showed me a better reader. Because the computerized docket didn't extend back as far as my great-grandfather's death, I had to ask about any earlier files, too (and unfortunately, I found out the court didn't have anything for him).
4. Keep a smile on your face. Even if you think you're bugging someone with your questions, a smile increases your chances of getting the help you need (as does a succinctly worded question).
5. Bring a camera. There was no place to photocopy the microfilmed records, so I photographed the reader's screen with my cell phone.
I don't have a tip for this situation: The file I most wanted to look for, a 1924 commitment hearing for my great-grandmother to the Cleveland State Hospital, was confidential—if it exists. Disappointing.
I politely asked enough questions (is it possible to request a search just to see if there's a file? how long are the records closed? what's the law declaring them closed? what's the procedure for having a file opened?) that I got to speak with a magistrate. He complimented my interest in genealogy, asked about my family history, and said that if the record exists—and chances are slim—the only way to have it opened would be a change in the law.
In the excellent book Annie's Ghosts: A Journey Into a Family Secret, journalist Steve Luxenberg describes his quest to uncover 1940s-era institutional records in Michigan for an aunt he'd only recently learned he had. I don't think I want to let this drop quite yet, but I'm also not sure I'm ready for a struggle like Luxenberg's. I'll dig a little and maybe be able to offer tips in the future.
Get Family Tree Magazine's guide to courthouse research, a $4 download, from ShopFamilyTree.com.
The Fold3 (formerly Footnote) World War II Collection is free through April 30. Records include Old Man's Draft Registrations (so-called because men ages 43 to 62 had to register), Missing Air Crew Reports, European Theater Army Reports, photos and more.
Ancestry.ca, the Canadian sister site to Ancestry.com, is offering free access to French Canadian records from April 17 through 22. Collections include the Drouin database of 37 million names in baptism, marriage and burial recordsfrom Quebec; the Tanguay collection on French-Canadian families; plus church records from Ontario, Nova Scotia, New Brunswick and New England.