--- Log opened Wed Sep 10 00:00:35 2025
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02:32 < hprmbridge> kanzure> qwen3-asr-flash and kimi-k2-think are out
02:32 < hprmbridge> kanzure> oh, nevermind. namespace conflict.
02:34 < hprmbridge> kanzure> https://k2think.ai/
02:55 < hprmbridge> kanzure> " The organized human SEMs recapitulate key hallmarks of post-implantation stage embryogenesis up to 13-14 days post-fertilization (dpf, Carnegie stage 6a), such as bilaminar disk formation, epiblast lumenogenesis, amniogenesis, anterior-posterior symmetry breaking, PGC specification, primary and secondary yolk sac formation, and extra-embryonic mesoderm expansion that defines a chorionic cavity
02:55 < hprmbridge> kanzure> and a connective stalk." https://www.biorxiv.org/content/10.1101/2023.06.14.544922v1
03:09 < hprmbridge> kanzure> what would it take in terms of energy, material and egg size to create an oviparous human fetal gestation? how large would the egg have to be? human pregnancy only requires +50,000 kcal although this is not a complete accounting of all energy and material inputs.
03:44 < hprmbridge> kanzure> "Spock explains that he will have to guess at some of these calculations, and he expresses concern that Kirk is not more worried. To which McCoy says: Spock, your guesses are better than most people's facts."
03:52 < hprmbridge> kanzure> "An oviparous human egg capable of supporting a fetus to full-term birth (~3.5 kg) would need to be about 5–6 kg in total mass, roughly the size of a football (~25 cm long and ~18 cm across). The breakdown would look similar to precocial bird eggs: about 2.5–3 kg of yolk (providing ~9,000–10,000 kcal), ~2 kg of albumen (mainly water and protein), and ~0.6 kg of calcium carbonate shell. This would
03:52 < hprmbridge> kanzure> give the developing embryo enough energy, water, protein, and minerals for growth, with calcium reserves more than sufficient for building a skeleton. The yolk provides several times the ~4,000–7,000 kcal the fetus itself requires, ensuring a safety margin, while the shell would need to be porous enough to allow 4 to 8 liters of oxygen per day to diffuse in over nine months. In short, such an egg
03:52 < hprmbridge> kanzure> would be very large, heavy, and energetically feasible. Diffusion, waste management, and water balance would be the main limiting challenges."
04:09 < fenn> but it could be squishy
04:16 < hprmbridge> kanzure> harden it and do fluid transfer in only one area with a through hole
04:20 < hprmbridge> kanzure> "cerebral organoids, where it is shown that limitations in diffusion and organoid size can be partially overcome by localizing metabolically-active cells to an outer layer in a sphere, a regionalization process that is known to occur through neuroglial precursor migration both in organoids and in early brain development."
04:40 < hprmbridge> kanzure> to prevent ischemia or hypoxia in small tissue culture or crafts, we should do long-term multi-needle injection of oxygen-releasing microspheres or hydrogels. or perfluorocarbon oxygen emulsions. after a few weeks of vascularization or angiogenesis you can then remove the needle and O2 supply and let the tissue survive on its own.
04:40 < hprmbridge> kanzure> "oxygen microbubbles" are another option
04:41 < hprmbridge> kanzure> i keep looking for a surgical option for a synthetic capillary that can be stitched through some tissue, haven't found anything yet. it just needs to be O2 permeable.
04:43 < hprmbridge> kanzure> IIRC jmil's work with 3d printing of perfusable vasculature was more about ex vivo printing and scaffolding, not about in situ surgery or working with existing tissue https://pmc.ncbi.nlm.nih.gov/articles/PMC3586565/
04:45 < hprmbridge> kanzure> maybe silicone or PDMS micro tubes would be adequate?
04:48 < hprmbridge> kanzure> some weird PDMS artificial lung implant stuff. ok.
05:01 < hprmbridge> kanzure> "Oxygen-releasing sutures for skin grafts" https://www.sciencedirect.com/science/article/pii/S2095809923002072 but the source of oxygen here is non-renewable? guess it only needs to last until vascularization or angiogenesis takes over.
05:18 < hprmbridge> kanzure> okay what about, selectively breed an animal that has super awesome microvessels and we fragment and chop them up for delivery with tissue blocks or implanted cell therapies. this should allow for xenotransplantation or xenografting incorporation of foreign blood vessels and faster vascularization.
05:21 < hprmbridge> kanzure> "Transplantation of adipose tissue-derived microvascular fragments promotes therapy of critical limb ischemia" https://pmc.ncbi.nlm.nih.gov/articles/PMC10350266/ alright but how fast is it oxygenating? how much faster than normal angiogenesis?
05:24 < hprmbridge> kanzure> "Bioengineered human vascular networks transplanted into secondary mice reconnect with the host vasculature and re-establish perfusion" https://pmc.ncbi.nlm.nih.gov/articles/PMC3242724/ (2011) yeah but it takes 3 days! maybe oxygen sutures can last that long? or the other in situ oxygenation materials schemes...
05:32 < hprmbridge> kanzure> "In the present study, we aimed to test whether ECFC/MPC-bioengineered human vessels originally perfused at one site could become reperfused in a secondary site. We show, by in vivo staining and ultrasonic imaging analyses, that ECFCs/MPCs rapidly formed anastomoses and increased MVD and perfused vascular volume over 7 days in donor mice. After transplantation, perfusion was reestablished by day
05:32 < hprmbridge> kanzure> 3. Chen et al demonstrated that a 7-day in vitro preassembly step, in which ECFC-derived endothelial cells and fibroblasts were coincubated in a fibrin gel, accelerated anastomosis with host vasculature after implantation.7 In contrast, the present study shows that prebuilt perfused human vessels are transplantable from one in vivo site to another. Perfusion of transplanted human blood vessels,
05:32 < hprmbridge> kanzure> first detected at day 3 and increasing with time to a physiologic range, demonstrates an important new feature of ECFC/MPC-bioengineered blood vessels, the ability to be transplanted and reconnect to the vasculature in a new site and rapidly reestablish perfusion."
05:46 < hprmbridge> kanzure> "Advances in microneedles-based drug delivery system on promoting wound healing" https://www.sciencedirect.com/science/article/abs/pii/S0142961214002051 no let's instead continue to not deliver resources directly to tissue damage
05:54 < hprmbridge> kanzure> bet you could use aggressive tumors with hypervaacularization, chop them up, use segmented fragmented capillaries and glue them to the targeted tissue block. you might get even faster vascularization this way.
06:00 < fenn> and aggressive tumors?
06:01 < hprmbridge> kanzure> Pick a type we can trivially treat?
06:02 < hprmbridge> kanzure> "skin micro dialysis" diagram, apparently only used as an alternative to repeated blood sampling?? wtf https://cdn.discordapp.com/attachments/1064664282450628710/1415321504375111730/image0.jpg?ex=68c2c85e&is=68c176de&hm=74e74fb8ad20c0fc24268c213a12d96f328989e6c04220230ea1a1f157788867&
06:05 < hprmbridge> kanzure> skin microdialysis https://pmc.ncbi.nlm.nih.gov/articles/PMC6456961/ see Fig. 2
06:39 < hprmbridge> kanzure> hydrogel microneedle patch approaches are fine for continuous release of very small amounts of protein and growth factors, but oxygen is the primary resource needed, which requires continuous perfusion.
07:26 < kanzure> more people should try very hard to not be stupid. intentionally trying to not be stupid is a skill that must be developed over time.
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07:30 < L29Ah> is there VC for that?
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08:01 < kanzure> 404 acronym not found
08:13 < kanzure> "Novel intra-tissue perfusion system for culturing thick liver tissue" https://www.liebertpub.com/doi/abs/10.1089/ten.2007.0040 (2007) "the needles deliver nutrients and remove metabolites by interfacing to the angio-architecture low paths of the liver slice." looks like they inject culture media straight into the liver, possibly including oxygenation of the culture media. they suggest ...
08:13 < kanzure> ...switching to porous needles to deliver along the length of the needle tip instead of solely at the tip.
08:13 < kanzure> "The molecular diffusion distance is not more than a 100 to 200 micron distance from a supplying capillary.[31, 32]"
08:20 < kanzure> i don't understand their system diagram. are they draining the tissue anywhere? are they injecting into specific vasculature, or just using arbitrary tissue puncture for needle placement?
08:31 < kanzure> direct continuous perfusion delivery of culture media into tissue seems like the obviously correct thing to try to do? and i don't see any other studies doing it? what?
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08:32 < kanzure> from the department of crazy ideas: what about culturing capillaries, arterioles or other small blood vessels, packing them with lots of yummy nutritous well-chosen contents, and then surgically circularizing them so that they don't lose their contents, and then injecting these circularized micro-vessels into tissue to promote angiogenesis and vascularization.
08:34 < MuaddibLLM> Short answer: Khong et al. used interstitial delivery via a 7‑needle microarray inserted into thick liver slices (not specific vessel cannulation), with flow exiting into the surrounding bath/outlet of the chamber - think pressure-driven in, diffuse through angio-architecture, drain out; see the paper and a review that sketches similar setups and related work (Khong 2007: https://pubmed.ncbi.nlm.nih.gov/17708717/; 
08:34 < MuaddibLLM> review: https://pubmed.ncbi.nlm.nih.gov/32879734/; analogous brain-slice interstitial perfusion: https://pubmed.ncbi.nlm.nih.gov/19443039/).
08:34 < kanzure> oh, you can just PEG the two ends of the vessel together to make a circularized capillary vessel. it shouldn't really need to have circulation.. maybe.
08:46 < kanzure> that thick brain slice perfusion paper (with also an unclear diagram- where are the needles?) says "The formation of interstitial fluidic paths of low resistance diminishes the uniformity of tissue perfusion and ultimately results in lower viability." probably from wrongly tuning perfusion rate for tissue material properties.
08:47 < MuaddibLLM> There’s prior art for your “injectable microvessels”: adipose-derived microvascular fragments are injected as intact vessel segments that rapidly inosculate and reassemble into perfused networks in vivo, so leaving ends open is a feature not a bug vs PEG-sealed loops; see Laschke 2015 Trends Biotechnol https://www.cell.com/trends/biotechnology/fulltext/S0167-7799(15)00123-7, Frueh 2017 J Invest Dermatol 
08:47 < MuaddibLLM> https://www.sciencedirect.com/science/article/pii/S0022202X16322758, Später 2021 Front Bioeng Biotechnol https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2021.777687/full.
08:55 < kanzure> uhh someone should think about the implications of a viable cortical perfused tissue culturing technique with regards to either brain uploading, brain preservation, electrical interfacing, memory interrogation, etc
08:58 < kanzure> because larger perfusable chunks are presumably more useful than smaller slice cultures (which diffusion can support, maybe, but has less neuronal network topological integrity due to smaller tissue volume retained)
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13:22 < hprmbridge> kanzure> that heterozygous allele CRISPR article yesterday was written by the guy who was recently evicted from the esteemed position of president of stanford for uhh... fraud.
13:48 < hprmbridge> kanzure> what if you sliced the tissue, cut free micro channels, and then stitched the tissue back together, followed by needle perfusion to use the cut pattern for liquid and gas distribution
14:28 < hprmbridge> .monokhrome> There was some girl who was buried in bronze age denmark, due to unusual soil some of her brain was preserved 3000 years on and is in a jar somewhere. We should do this memory interrogation thing on it to find out what her life was like.
14:29 < hprmbridge> kanzure> do you mean the volcano brain people? not all the neurons are preserved or synapses...
14:30 < hprmbridge> .monokhrome> no this was in denmark, not italy
14:30 < hprmbridge> .monokhrome> https://en.wikipedia.org/wiki/Egtved_Girl
14:31 < hprmbridge> .monokhrome> all her bones had dissolved, but for some reason some of her brain was left
14:33 < hprmbridge> .monokhrome> the egyptians used to preserve the organs of mummies in special jars they buried with the mummies, but sadly not the brain
14:41 < hprmbridge> maclane> On my way.
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15:00 < L29Ah> .t https://www.cell.com/cell/fulltext/S0092-8674(25)00571-9
15:00 < saxo> Just a moment...
15:00 < L29Ah> Senescence-resistant human mesenchymal progenitor cells counter aging in primates
15:26 < hprmbridge> kanzure> does their approach count as "young blood rejuvenation" or not?
15:28 < L29Ah> no, as young blood thing is in fact young plasma
15:38 < L29Ah> but maybe the body cloning plan would work there too
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16:22 < fenn> looks like mixing in adipose derived vessels and capillaries into synthetic dermal regeneration template collagen scaffold helps skin heal faster https://ars.els-cdn.com/content/image/1-s2.0-S0022202X16322758-gr3.jpg
16:22 < hprmbridge> kanzure> it's over, you need to deliver oxygen to avoid ischemia
16:23 < hprmbridge> kanzure> surgeons are out of their minds.
16:23 < hprmbridge> kanzure> microneedle perfusion is the only way
16:23 < fenn> it is odd that this is not already a thing
16:24 < fenn> most tissue being implanted already has a vasculature network and it's the surgeon's job to merely hook it up
16:24 < hprmbridge> kanzure> for organs it's easier
16:24 < hprmbridge> kanzure> for small tissue, supermicrosurgery is not so common
16:25 < hprmbridge> kanzure> if there's no large scale circulatory port already in the tissue, then you need the tissue to be artificially maintained until angiogenesis and vascularization succeeds.
16:25 < fenn> how about shoving a blunt needle into the existing vasculature if it's too small, and deliver blood that way
16:25 < fenn> it could be biodegradable
16:25 < hprmbridge> kanzure> yes what a great idea
16:26 < fenn> is that what they already do? i don't speak surgeon
16:26 < hprmbridge> kanzure> They don't do this.
16:26 < hprmbridge> kanzure> https://diyhpl.us/~bryan/irc/chatgpt/ischemia.txt
16:26 < hprmbridge> kanzure> but they absolutely should.
16:28 < hprmbridge> kanzure> for blood you will want both an input and an output, else you get an uncontrolled bleed. however even just perfusion of oxygen would go a long way here....
16:28 < fenn> i don't think you can just run oxygen gas through tissue
16:29 < fenn> a constant small leak of something like plasma shouldn't be too bad if it's temporary
16:29 < fenn> like peritoneal dialysis
16:29 < hprmbridge> kanzure> if there is existing microvasculature, then it doesn't need to be a leak.
16:30 < hprmbridge> kanzure> if there is not, then you can still have one side of the tissue block driving pressure and the other side can be waste exit
16:30 < fenn> the existing vasculature is probably not a closed loop, especially if you're starting with chopped up pieces of vessels
16:30 < fenn> yeah or you could wrap it in plastic to contain the blood
16:30 < hprmbridge> kanzure> no you want it to incorporate into surrounding tissue
16:31 < fenn> ok there are a lot of use cases
16:31 < hprmbridge> kanzure> oh, sorry. yes.
16:31 < hprmbridge> kanzure> broadly, if the problem is ischemia, then the problem can be mechanically fixed instead of not fixed.
16:33 < fenn> this seems like it would take decades to get through the medical regulatory process
16:33 < fenn> would an ER surgeon rip the perfusing robot off the patient?
16:33 < hprmbridge> kanzure> maybe, but very easy to test with animals, 3d printed tissue blocks etc
16:36 < fenn> i wonder why we consider this dystopian https://cyberpunk.fandom.com/wiki/Trauma_Team
16:36 < fenn> it's better than current medical practice
16:36 < fenn> imagine if capitalism actually optimized for medical outcomes
16:37 < hprmbridge> kanzure> I'm not really sure why this ischemia thing is a blindspot
16:38 < fenn> trauma team's rate of $100 a minute sounds like insane cyberpunk dystopia, but it's the actual rate charged to me in a recent hospital visit that did absolutely fuck-all while i sat in a waiting room
16:38 < hprmbridge> kanzure> hmm well doctor i guess tissue just dies without nutrition and oxygen lol oh well on to the next patient?
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17:22 < hprmbridge> kanzure> "Scalable tissue biofabrication via perfusable hollow fiber arrays for cultured meat applications" https://www.cell.com/trends/biotechnology/abstract/S0167-7799(25)00085-X
17:22 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1415492714790654064/image0.jpg?ex=68c367d1&is=68c21651&hm=c409bf79065d43593d0cb85ccece5281f26022d6db48ac263cc5076cc6199ce5&
17:29 < hprmbridge> kanzure> someone should do that for cortical tissue blocks.
17:41 < hprmbridge> kanzure> "Bioengineering vascularization" https://journals.biologists.com/dev/article/151/23/dev204455/363262/Bioengineering-vascularization under the section "Regenerative medicine" there's some weird stuff.
17:41 < hprmbridge> kanzure> "An alternative implantation approach involves the use of a macro-vessel (in the millimeter range) accompanied by the surrounding microvasculature. The macro-vessel is typically surgically connected to the host's circulatory system by direct anastomosis. For example, we surgically connected AngioChip to the femoral vessels of rat hindlimbs, demonstrating an immediate blood perfusion (Zhang et al.,
17:41 < hprmbridge> kanzure> 2016) (Fig. 3B). Larger 3D printed vessels have also been surgically anastomosed in rats or pigs (Table 2) (Galván et al., 2021). The utility of engineered vasculature can also extend to tissue flap transplantation. In this scenario, the engineered vasculature is initially implanted into one region and subsequently surgically relocated to another, offering a vascularized bed for both soft and hard
17:41 < hprmbridge> kanzure> tissues, while minimizing trauma to the donor site (Table 2) (Shandalov et al., 2014; Redenski et al., 2021)."
17:42 < hprmbridge> kanzure> "Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis" https://pmc.ncbi.nlm.nih.gov/articles/PMC4879054/
17:43 < hprmbridge> kanzure> Figure 6. Surgical anastomosis of the cardiac tissue microchip to rat femoral vessel. https://cdn.discordapp.com/attachments/1064664282450628710/1415497988423286907/image0.jpg?ex=68c36cbb&is=68c21b3b&hm=2c34a9a7b82842485610e8cab899a60e71634b5146104bc500ae0849e1909be8&
17:46 < jrayhawk> welp, google has finally banned html browsers
17:47 < jrayhawk> pasky: do you know of any movement in the html browser ecosystem on support for HTTP 402? e.g. https://github.com/lightninglabs/L402 or what have you
17:48 < hprmbridge> kanzure> try browsh?
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19:07 < hprmbridge> kanzure> "hydrogel suture" https://www.nature.com/articles/s41467-024-45144-y with a syringe pump. used to join vessels, deliver drug to cardiac tissue, etc.
19:18 < hprmbridge> geraldmahony> TTI is not a bad business model
19:21 < fenn> what if we literally had gangs that performed life-saving medical services for money
19:21 < fenn> are they going to send in the swat team to stop them?
19:22 < hprmbridge> kanzure> what if the gangs had really good opsec
19:22 < fenn> crips do chronic and bloods do acute
19:23 < hprmbridge> kanzure> hmm do i want medical licensing cartel to be taken over by the cartels
19:30 < L29Ah> if gangs had opsec they wouldn't have many customers
19:32 < L29Ah> could crowdfund privacy-aware communications and payments to ease the PR job of cartels but it would be really hard to outcompete Visa and Meta for normies' attention
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--- Log closed Thu Sep 11 00:00:36 2025