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What I say is always stick to fact based logic, always stick to known logical frameworks, always look for results before anything, like over detailed theory and stick to the results. Do not promote an authority figure, its ok to reference though. Learn from the history of the subject.
What I say is always stick to fact based logic, always stick to known logical frameworks, always look for results before anything, like over detailed theory and stick to the results. Do not promote an authority figure, its ok to reference though. Learn from the history of the subject.
Yes we need results.
Yes we need results.
Actually RXi-109 should be more effective then EXC-001 because it is based on more advanced sd-rxRNA technology (it is more effective than standard RNAi technology) and because of that RXi-109 will be able to inhibit CTGF much more then EXC-001, so results will be better then this:
Something about EXC-001:
http://www.isispharm...C001_Poster.pdf
And there where no problems with EXC-001 in phase 2 clinical trials like there were problems with Juvista in phase 2 clinical trials (phase 3 trials will begin in 2013)... so EXC-001 is more effective then Juvista and RXi-109 will be more effective then EXC-001... but I don't know... still I have serious doubts that they will achieve something like 90% reduction of scarring by targeting only a single gene... anyway I hope it's not a scam like Renovo and I hope that Craig Mello and other people in company's management will not exercise all of their stock options before announcement of phase 2 and phase 3 clinical trial results... but if they do so (like Mark Ferguson did in 2007) then we will know it is another Juvista-like scam...
Hey Seabs can you explain me something about that hydrogel research paper please:
http://www.pnas.org/...8.full.pdf html
Skin Maturity Quantification. The skin structure on day 21 was assessed using
H&E-stained histologic sections, according to previously published methods
(39). At 21 d after the burn, we used specific criteria to assess each wound
histologically for the number of hair follicles, epithelial maturation, and
dermal differentiation.
...
The grading for dermal differentiation used the following
criteria: grade 1, thin, dense, and monotonous fibrosis; 2, thicker but still
dense and monotonous fibrosis; 3, two layers but not completely discreet;
4, two discreet layers with superficial fibrosis and loose alveolar tissue within the deep layer.
What does it mean 'dermal differentation'? I don't understand grade 3 and grade 4 - some 'layers' that are not 'completely discreet' are mentioned and some 'superficial fibrosis' and 'loose alveolar tissues' are mentioned - I don't know what does it mean?
And I don't understand whether this hydrogel can regenerate open dermal wounds that are NOT stitched?
You sometimes highlight benchmarks by using previously set methodological standards (e.g. you can measure how far someone can jump in the long jump and compare it to previous standards etc. But youd not be able to highlight your result against something for the long jump if there was no previous standardised criteria in the long jump assuming you are the first to do the long jump) . Imo all they are doing is showing the standards they have used that have been used in the past in other experiments were skin maturity was assessed.
And in the paper on the first sentence of the paragraph they have explained how they assessed the skin maturity results at day 21 using previous benchmark standards someone else has used.
(Btw on the paper they assessed the maturity over the whole experiment, e.g. at day 7 and 10 they noted the scaffold had been digested, whereas the control scaffold had not. And Im sure somewhere I read that they checked the maturity of the skin way after day 30. But I dont think there were previous standards set for checking the skin maturity at day 10, or if there was they did not know about it.)
"Skin Maturity Quantification. The skin structure on day 21 was assessed using H&E-stained histologic sections, according to previously published methods (39).
Which according to cite 39, was a standard that was previously used here >>>> Ehrbar M, et al. (2004) Cell-demanded liberation of VEGF121 from fibrin implants induces local and controlled blood vessel growth. Circ Res 94:11241132.
And then they went onto explain the indicators used in the previously set standard like the differentiation of the tissue that was a standard indicator previously designed and used by someone else. That someone elses indicator standard did not have any more criteria. Also the graded criteria 1, 2, 3, and 4 would have been decided on before hand in the design phase, and would have not been wrote up afterwards with the conclusion. The grades are just indicators used in a standard which was decided upon before the experiment and then used in this experiment, that were used previously in another seperate experiment (in cite 39). They just used this standard to explain the skin maturity at day 21. All they are doing there is explaining how they decided to benchmarked the hydrogel against previously set test standards already established for skin maturity.
They did not set or design these standards, they just decided to use these previous set standards.
But the key logic here is, if there was any scar you would not get hair and micro-glands in a third degree burn. No tissue bar scar regenerates in scar, a key logical fact. And they would not announce complete regeneration in the paper. And if a wound reepithilizes in under 21 days you do not get scar as a scar loop takes over 21 days to scar.
Regarding the stitches. The design of the experiment did not mention they secured the wound with stitches, they explained that they created a third degree burn cut out the full thickness burn, and inserted the hydrogel and used a dressing to keep it securely in place Off the top of my head IMO I imagine that putting stitches in would be a problem, Ive read that stitches can create scar when the body tries over time to eject the stitch or digest the stitch. Anyway I'd imagine stitching through the hydrogel would be like stitching jelly. Maybe in certain types of wound this may mean youd have to revise any part of the long wound messed by stitches if you stitched...
And then they went onto explain the indicators used in the previously set standard like the differentiation of the tissue that was a standard indicator previously designed and used by someone else. That someone elses indicator standard did not have any more criteria. Also the graded criteria 1, 2, 3, and 4 would have been decided on before hand in the design phase, and would have not been wrote up afterwards with the conclusion. The grades are just indicators used in a standard which was decided upon before the experiment and then used in this experiment, that were used previously in another seperate experiment (in cite 39). They just used this standard to explain the skin maturity at day 21. All they are doing there is explaining how they decided to benchmarked the hydrogel against previously set test standards already established for skin maturity.
They did not set or design these standards, they just decided to use these previous set standards.
Well I don't know, that chart shows the skin maturation slightly above 3... and I don't know what that "T" above the scale stands for? If we can calculate that "T" then the skin maturation is about 4.5... and there are some horizontal ] with * and ** - I don't know what is that stands for?
And it's strange that hydrogel can regenerate full thickness excisional wounds in only 3 or 5 weeks when we know that salamanders can regenerate same kind of wounds completely in 3 to 6 months...
By the way here is another discussion about that hydrogel - some people think that it could lead to a definitive cure for baldness (because it creates hair follicles)
http://www.baldtruth...read.php?t=7090
If it is a definite cure for scars and for baldness then what is a market size for that hydrogel? $4 (scars) + $10 billion (baldness) = $14 billion a year in the US alone and I would say at least $50 billion globally... 
then this hydrogel could conquer the world so easily, it could be the next Microsoft and will have another Forbes billionaires from JHU soon... then why it cannot get NIH funding!!!??
And then they went onto explain the indicators used in the previously set standard like the differentiation of the tissue that was a standard indicator previously designed and used by someone else. That someone elses indicator standard did not have any more criteria. Also the graded criteria 1, 2, 3, and 4 would have been decided on before hand in the design phase, and would have not been wrote up afterwards with the conclusion. The grades are just indicators used in a standard which was decided upon before the experiment and then used in this experiment, that were used previously in another seperate experiment (in cite 39). They just used this standard to explain the skin maturity at day 21. All they are doing there is explaining how they decided to benchmarked the hydrogel against previously set test standards already established for skin maturity.
They did not set or design these standards, they just decided to use these previous set standards.
Well I don't know, that chart shows the skin maturation slightly above 3... and I don't know what that "T" above the scale stands for? If we can calculate that "T" then the skin maturation is about 4.5... and there are some horizontal ] with * and ** - I don't know what is that stands for?
And it's strange that hydrogel can regenerate full thickness excisional wounds in only 3 or 5 weeks when we know that salamanders can regenerate same kind of wounds completely in 3 to 6 months...
By the way here is another discussion about that hydrogel - some people think that it could lead to a definitive cure for baldness (because it creates hair follicles)
http://www.baldtruth...read.php?t=7090
If it is a definite cure for scars and for baldness then what is a market size for that hydrogel? $4 (scars) + $10 billion (baldness) = $14 billion a year in the US alone and I would say at least $50 billion globally...
They designed the test with a hypothesis that did not expect complete regeneration but would get better healing through the speed of the digestion of the hydrogel, the result was a suprise. It digested fast and brought complete regeneration. In the pdf I have I have a chart that shows at day 35 the thickness of the skin treated by the hydrogel is the same thickness size as normal skin. It also shows that at day 21 the control and the untreated wounds had roughly the same hair numbers per mm (roughly 0 to 1) and the hydrogel had 10 to 15 hairs per mm.
I reckon a market is big but imo but I would not go as far to say a market for this (or almost anything for that matter) would be the making of the next microsoft (the potential for microsoft and google is that everyone could realistically have a pc one day and through this, this market is extreme and rare. IMO only some established percentage of people have the problem of scars, but those that have them suffer immensely.) Also I believe the market of 4 billion is probably overstated somewhere and probably through this unreliable, it is a forward sounding crystal ball statement imo. Anyway talking about markets is no where as important as removing the immense suffering that happens in 3rd degree burns.
I was reading something the other day on the NIH funding page that an R-something (there is three of them) can take 5month+ to get funding.
I don't know, if you're right then they've made a quite confusing bar chart, I mean they could draw it so that skin differentiation for hydrogel shows 5 or 6 or 7 or they could draw that bar chart without that rectangular bar for the hydrogel - instead they could just write 'complete skin differentiation' or something like that.
And this photo looks very, very promising (if it is not Photoshop manipulation) - actually I don't care how that hydrogel works or how huge is the market size for it, the only thing that is important is that it works 
(if it really works, of course)
although it looks like hair is not so densely distributed at the site of the injury like at the rest of the skin - so the other question that we should ask ourselves is how many hair follicles are at the site of the injury and how many hair follicles are at the uninjured skin? 
And here are some intriguing quotes:
The results showed that the dextran hydrogel promoted significant skin maturation;
Why 'significant', why not 'complete'?
Histological analysis revealed that, compared to wound healing when treated with the control scaffold, dextran hydrogel yielded an accelerated healing kinetics, which resulted in regenerated skin with a defined underlying collagen layer after 3 weeks of treatment
What is that mean 'defined underlying collagen layer'?
And it is known that maturation and remodeling phase during wound healing in mammals and salamanders lasts for 6 months or 12 months or something like that, so how it is possible that with this hydrogel it lasts for only 3 to 5 weeks? Are there any changes after the 5th week or everything is over then?
I don't know, if you're right then they've made a quite confusing bar chart, I mean they could draw it so that skin differentiation for hydrogel shows 5 or 6 or 7 or they could draw that bar chart without that rectangular bar for the hydrogel - instead they could just write 'complete skin differentiation' or something like that.
And this photo looks very, very promising (if it is not Photoshop manipulation) - actually I don't care how that hydrogel works or how huge is the market size for it, the only thing that is important is that it works
although it looks like hair is not so densely distributed at the site of the injury like at the rest of the skin - so the other question that we should ask ourselves is how many hair follicles are at the site of the injury and how many hair follicles are at the uninjured skin?
And here are some intriguing quotes:
The results showed that the dextran hydrogel promoted significant skin maturation;
Why 'significant', why not 'complete'?
Histological analysis revealed that, compared to wound healing when treated with the control scaffold, dextran hydrogel yielded an accelerated healing kinetics, which resulted in regenerated skin with a defined underlying collagen layer after 3 weeks of treatment
What is that mean 'defined underlying collagen layer'?
And it is known that maturation and remodeling phase during wound healing in mammals and salamanders lasts for 6 months or 12 months or something like that, so how it is possible that with this hydrogel it lasts for only 3 to 5 weeks? Are there any changes after the 5th week or everything is over then?
I cant see your image but if it is the one on page 5 (I think) then that to me looks like normal mouse hair were the wound was treated imo. Regarding remodelling, our non scarred tissues are always remodelling, creating new non scarred tissue and ejecting dead tissue throughout our lives, tissue never stands still. Regarding the hydrogel, wouldn't the hydrogel be finished its job in the wound as soon as it is digested after about 7 to 10 days and the remodelling of the tissue be the beginning of a lifetime process?
Regarding the definition and interpretation of certain words and phrases I do not know. I mean I've used words which have been interpretated different, you have and everyone has.. Again what I stick to are the concluded facts, that it regenerated glands and follicles, It reepithilized the skin by day 14 (under 21 days), it rapidly digested the hydrogel, it had complete regeneration were the control and non treated did not ect.
So..when hydrogelitsgonna beonsale/its works or not?
It is still waiting for funding by the looks of it.
Yes, it is the one on page 5, I'm just curious about this sentence:
Histological analysis revealed that, compared to wound healing when treated with the control scaffold, dextran hydrogel yielded an accelerated healing kinetics, which resulted in regenerated skin with a defined underlying collagen layer after 3 weeks of treatment
What is that collagen anyway I don't know? 'A defined underlying collagen layer' - is it a normal skin or a scar?
This sentence is ecouraging:
By day 21, burn wounds treated with hydrogel developed a mature epithelial structure with hair follicles and sebaceous glands. After 5 weeks of treatment, the hydrogel scaffolds promoted new hair growth and epidermal morphology and thickness similar to normal mouse skin.
What is that 'edipermal morphology'? is that the appearance of skin surface r what? And that photo from page 5 was taken after 5 weeks, not after 3 weeks.
This is some other research paper published by Sharon Gerecht, some other hydrogel is mentioned and a higher level of MMPs (matrix metalloproteinases) is mentioned too, I don't understand all details but maybe the hydrogel can increase the level of MMPs and thus accelerate re-epithelization as it normally happens in salamanders:
Epidermal morphology looks to me like a phrase for tissue maintenance and remodelling.
Hey Seabs what is that collagen, can you explain me please?
Collagen??? All our tissues have collagen. But scarring is an over expression of collagen that blocks off cell comunication and regeneration. Epidermal morphology to me just looks like a phrase for observing the turnover of cells over time in skin, e.g. the edidermal morphology on your wrist if non scarred will have normal skin turnover, an observed normal epidermal morphology over time; were you can assess the tissue over time, as your tissue remodels etc.
Ok, thanks, I hope that phrases like 'defined underlying collagen layer' and 'edipermal morphology similar to normal mouse skin' stand for a normal skin, and that skin scars are actually disorganized, overproduced collagen formed along lines of tension on the skin.
And now I get it how hydrogel works - it's the newest promising technology in regenerative medicine, it's kind of a 'smart' techology that can bulid complex tissue structures (like skin and other tissues); it's actually an artificial regenerative ECM which can properly distribute cells in all 3 dimensions.
BTW beside that dextran hydrogel there are 1000 other hydrogels, here are a lot of explanations how they work:
Smart, self-healing hydrogels open far-reaching possibilities in medicine, engineering
http://www.jacobssch...ase.sfe?id=1175
Hydrogels in Regenerative Medicine
http://www.tissueeng...ve medicine.pdf
Collagen scaffolds for bone healing
BioTime & Glycosan - HyStem Hydrogels
Tissue Engineering: New Approaches And Advancements
Vlad says: "BTW beside that dextran hydrogel there are 1000 other hydrogels, here are a lot of explanations how they work"
my question for all is: if in the past there are 1000 others hydrogels...why this new dextran hydrogel its so different? I hope this not scam! Im scared about it...after the scam of juvista im so depresed...i hope hydrogel dextrn not scam...really i can not understand why its so different dextran hydrogel than others hydrogels.
Here is a hydrogel for car scrathes - scar free healing for cars 
it is able to completely regenerate 'scars' on the paint in less than a minute!
Together with partners in the USA and Switzerland, they have developed a polymer-based material that can heal itself when placed under ultraviolet light for less than a minute.
'polymer-based material' and 'UV light' - it sounds just like this hydrogel stuff, isn't it?!?! 
I mean - WHAT ELSE COULD IT BE?
I guess that hydrogel technology will be useful in industry and materials and other fields outside of regenerative medicine.
Vlad says: "BTW beside that dextran hydrogel there are 1000 other hydrogels, here are a lot of explanations how they work"
my question for all is: if in the past there are 1000 others hydrogels...why this new dextran hydrogel its so different? I hope this not scam! Im scared about it...after the scam of juvista im so depresed...i hope hydrogel dextrn not scam...really i can not understand why its so different dextran hydrogel than others hydrogels.
Well I guess because that dextran hydrogel can somehow recruit stem cells inside it, others cannot, actually their first intention was to induce stem cells and growth factors into it but they figured out it works without stem cells and growth factors, that was a surprise. And other hydrogels are good but not as good as that dextran hydrogel, for example this hydrogel is reportedly quite successful in coping with keloids:
http://halscion.net/...bruary-15-2012/
And I think that is not a scam because it is quite easy to make a scam when you announce that you own some 'scarless healing' solution (then you can set up your company, get a good management contract and stock options and sell all of it before phase 2 and phase 3 clinical trials and earn 16 million pounds in 5 years), it's different with scar free healing solution, it's very hard to make a scam when you announce that you own some SCAR FREE healing solution that can COMPLETELY REGENERATE skin wounds (especially if it includes regeneration of sebaceous glands and hair follicles) - so in that case there are only two extreme possibilities: scars are observable or are not observable; sebaceous glands and hair follicles are observable or are not observable - there is no third possibility, so if their financiers observe even a small scar and if they don't observe sebaceous glands and hair follicles in mice then they would ask 'WTF IS THIS?', in the case of scar free healing there is no so much room for endless manipulations and lies.
Actually my biggest fear is WILL IT WORK IN HUMANS AS IT WORKS IN MICE!!!???
BTW here are some other hydrogel explanations:
Cells and Gels for Tissue Engineering and Regenerative Medicine
Combinatorial Polymers Scaffold Library
3D hydrogels for tissue engineering
my question for all is: if in the past there are 1000 others hydrogels...why this new dextran hydrogel its so different? I hope this not scam! Im scared about it...after the scam of juvista im so depresed...i hope hydrogel dextrn not scam...really i can not understand why its so different dextran hydrogel than others hydrogels.
Basically the hydrogel only has to differ in one small way for it be more effective than others. It may not be very different but it is seemingly different enough.
I personally haven't been thinking about scarless healing for quite some time now. I've just been getting on with things the best I can. The other day I saw myself in the mirror in some place when I was out and about and I saw my scar again. It didn't bother me that much to be honest. I'm out and about and only sporadically someone will react in a negative way. For instance someone will choose not to hide the fact that they don't think it's attractive and will communicate this to me using facial expressions. But that doesn't hurt me.
Here are some other research papers that I've just found out, they mention both hydrogels and dextran:
Hyaluronic Acid-Based Hydrogels: from a Natural Polysaccharide to Complex Networks.
http://www.ncbi.nlm....88/?tool=pubmed
and here are some interesting quotes from this paper:
Enzymatically crosslinkable HA has been synthesized by coupling tyramine to HA, directly109, 110 or via the grafted dextran.
These nanostructure hydrogels may be applicable as regenerative patches for skin and other tissues.
The presence of HA in the ECM of the injured tissues underscores its relevance in wound healing. HA content usually increases very quickly at scarless fetal wounds due to the reduced expression of proinflammatory cytokines (such as IL-1 and TNF-alpha) that are responsible for the down regulation of HA synthesis. HA expedites the delivery of solutes and nutrients to the wounded tissue because of its high water absorption capacity and its ability to stimulate inflammatory signals for wound healing. A HA-rich wound matrix may also facilitate cell motility and proliferation that are essential for wound repair.13, 25, 26 While the intact HA maintains the tissue in a hydrated state, the degraded HA released into the wound promotes cell proliferation, cell migration 27, 28 and angiogenesis,29 facilitating the scarless wound healing processes. The essential roles of HA in would healing justifies its utility in tissue repair and regeneration. 10
And here are some older papers:
Improvement of stem cell viability in hyaluronic acid hydrogels using dextran microspheres.
http://www.ncbi.nlm....pubmed/20537250
Enzymatically-crosslinked injectable hydrogels based on biomimetic dextran-hyaluronic acid conjugates for cartilage tissue engineering.
http://www.ncbi.nlm....pubmed/20116847
This one is interesting:
human embryonic stem cells + dextran-based hydrogel = enhanced vascular differentiation
Bioactive hydrogel scaffolds for controllable vascular differentiation of human embryonic stem cells
Lino S. Ferreira,* Sharon Gerecht, Jason Fuller, Hester F. Shieh,* Gordana Vunjak-Novakovic, and Robert Langer*||
http://www.ncbi.nlm....les/PMC1903348/
I guess that dextran hydrogels are previously known to scientists but they didn't know it can be used for skin regneration (scar free healing), they just haven't tried it for that purpose.