Podcast #119: Tendon Gel (The Interfascicular Matrix) with Hazel Screen


“Tendons are fiber composite. It’s collagen fibers that are surrounded by a soft gooey matrix, it’s how we make fiber composites if we try to make them in industry, tendon does it for us naturally.”

“The strains that the whole tendon could see were like twice as much as the failure strain for the fascicle.”

“Tendon is nearly all collagen. It’s very dense, very thick… there’s a layer that surrounds them and it’s like a gel… thick fibers with this much softer gooey gel surrounding them.”

How many fascicles in a tendon: “it is massively different.”

Mouse: “The entire tendon [Achilles] is roughly the thickness of one fascicle.”

“Fascicles seem to be roughly the same size in every species.”

“There is a similar kind of soft proteoglycan matrix between the collagen all the way through the hierarchy… but the IFM is a thicker layer, very clear, very defined cell population in it.”

“All the way through the hierarchy is a hydrated gel… full of proteoglycans (that attract water) that make a very hydrated gel.”

“Most of the elastic in tendon is in that region [IFM].”

“You don’t want your tendons too stretchy [elastin]… so you need something that’s quite stiff [collagen].”

“You strain a piece of tissue, collagen stretches a little bit… but the stretch in the tendon is enabled by the fascicles sliding, so one shears next to another… the proteoglycan gel will allow that… but that needs to bounce back, so presumably the elastin is in there to allow recoil.”

“There’s a lot of decorin between fibrils. We find a lot less decorin in the IFM. Lubricin shows up quite heavy [in the IFM].”

“In the horse SDFT, the tendon stretched twice as much as the fascicles. In the positional tendon, they were really quite a lot closer.”

“The fascicles in those two tendons types [positional and energy storing] were exactly the same… collagen seems to be collagen seems to be collagen… we’re not seeing any difference in the mechanics of the fascicles of all these different tissue, but the whole tendon properties are really different and it seems to be coming from that Interfascicular region.”

“There’s a really very active cell population specifically in the interfascicular matrix. The cells in fascicles don’t seem to do a huge amount.”

“The ability for interfascicular matrix cells to turnover the matrix seems to be an order of magnitude better.”

Tissue renewal: “We see the rate at which that happens in the IFM is much faster than in the fascicles themselves.”

“You look at aging, the collagen doesn’t change, the fascicles have the same properties, the same behavior, the IFM steadily gets stiffer… it becomes harder to allow that shearing and sliding between fascicles.”

“The tendon can’t be expected to strain uniformly, it just doesn’t make sense. With a horse, as it stretches, it goes round the fetlock joint, so you have to stretch it round a bend. If you stretch anything round a bend, the outside’s got to stretch more than the inside… so immediately, you’ve got to have that ability to have non-uniform strains and movement across the tissue.”

Achilles: “You have to allow those muscles to pull different parts of the tissue and for them to move independently or you’re going to start to get damage… if the IFM becomes stiff, you stop enabling movement sliding and non-uniformity of strains across the tissue, you start to load some parts too much, you start to get damage across that structure, and that’s why with aging (as it gets stiff), you’re much more prone to injury.”

IFM getting stiffer: “it seems to be a bit less hydrated, we do see some changes in composition [proteins, PGs]… and the cells themselves start to change phenotype.”

“If you apply 10,000 cycles, you stop there and you look at the response in the tissue… all of that [cell response to overload] was localized to the IFM.”

Nerve ingrowth: “When you do get ingrowth, it tends to ingrown within the interfascicular region, that’s where the blood vessels are… The blood vessels run through the IFM, it’s a bit more spacey, there’s space for this sort of stuff [ingrowth] to happen.”

Early tendon overload: “There is no structural change, structurally the tissue looks perfect, this is a cellular response.”

Chronically overloaded ‘mush matrix’: “At the end point, there is no clear distinct IFM. And once you haven’t got that, you have no nice clear ability for the tendon to strain properly, to do its shearing, to be able to load non-uniformly, and that’s when you’ve got a tendon that’s gonna be difficult to manage.”

Rupture: “you might have a region in the middle that’s stiff [rupture], it’s never gonna be good, but if you can get the rest of the tissue to function well around it, you can probably get reasonable function out of it.”

Viscous Properties

“If you take an isolated piece of tissue and you strain it and you hold it under a set amount of strain, we know that that force will steadily drop off, in theory to nothing if you wait long enough… when you started, each collagen fiber was under a certain amount of strain, we know that they are pulling back, it’s got to be shearing/sliding within the matrix that’s enabling that. Collagen is reasonably stiff, it doesn’t want to be stretched. If you hold it, the collagen will return to its original length because the fibers will shuffle, they’ll move. The matrix around them will enable that.”

“The interfascicular matrix is gonna allow that reorganization to basically take the load off the tissue and return each collagen fiber to an unstrained state where the whole tendon is longer than it was when we started.”

“Any material, it requires energy to be strained, as you put energy in to stretch it, if you’re holding it at that strain rate, if it can release that and go back to its original length, it will. Your whole unit, you put in energy, you’re holding, it will try to dissipate that by moving around water, moving around molecules, and letting the collagen structures relax.”

“Over 5 minutes, if you applied 8% strain to the fascicles, the force would drop by 50% at the end of the 5 minutes… over the first minute, you get a lot of water movement, structural changes in that tissue, a relaxing of the load.”

“If you look at the thickness of the tendon in a stress relaxation state, the whole tendon gets thinner.”

Stress relaxation tests: “The entire fascicle would get hugely thinner (half over 5 minutes)… but at a molecular level, they [collagen] seemed to imbibe water, they seemed to get fatter.”

“All stress relaxation is is a structure redistributing the strain that it’s under to be in its minimal energy state. It doesn’t want to be stretched so it’s trying to release that stretch. Think of wiggling, getting comfortable, moving things around to release that strain on it.”

“To creep a tendon, you have to hold the force… you’re putting a constant force on it and it gets longer and longer and longer… you grip one end and you hang a weight off the other end, if you do it for long enough, the tendon will creep until it snaps.”

Elastic Properties

“You’re just not giving time for time dependent effects to occur… the faster you strain a piece of tissue, the stiffer it is. The less time you allow for shearing, sliding, water movement, anything else.”

“If you do very fast movements, the IFM has to allow shearing and sliding, it can’t be just a slow, viscous, time dependent response. It needs to be able to allow shearing quite rapidly.”

Slow vs. Fast Movements

“What’s physically happening is the same thing, you’re just allowing a lot less time for it, and by allowing less time, you’re allowing less time for water to move, so you’d expect the whole tissue to behavior more stiffly, the collagen behaving more stiffly, the IFM behaving stiffer, allowing a little bit less shear.”

“Early in injury, you want to start encouraging sliding and that requires a bit of holding and allowing some time for these shearing movements and then you need to gradually ramp that up.”

Fascicles: “I don’t they can run from the muscle to the bone… take the Achilles, it starts one shape and it ends another. It’s got different thickness from the top to the bottom.”

“The fascicles themselves are helical… it’s like you’ve got these little helical springs of fascicles within the tissue.”

“It’s an ongoing ‘we don’t know’ how long the fibrils are or the fascicles are or any of the structures in tendon.”

“We’ve done a spectrum in horses, so we went from 2 (skeletally mature) to 28-30, and you can plot a straight line through the stiffening of the IFM.”

IFM stiffness with age: “I think there’s this steady accumulation.”

Avoiding IFM stiffening: “Heavy slow loading ought to allow sliding and keep it moving. I have no idea if that is true of not.”

“If you put all of the cells from a tendon and plate them on plastic and grow them, within a couple of weeks you will have nothing but the fascicular matrix cells left, all the IFM cells will just stop growing because they don’t like the stiff substrate of tissue culture plastic… they live in this soft, hydrated gel.”

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Other contact info: https://www.sems.qmul.ac.uk/staff/h.r.c.screen