The Tissue: Issue #4
It's not brat summer. It's tendon summer.
Hello enthusiasts for living materials of all sorts,
Summer is burning away, and as much as it pains me to admit, this is not the brat summer Charli XCX promised me (but you should still ride the rollercoaster that is brat ). By all accounts, it’s actually tendon summer. And as *dumb* as that introduction was, it’s all thanks to the three papers in this month’s Tissue that feature the tendon front and center, two of which detail phase I/II clinical work in human patients.
It’s also tendon summer because my bike decided to flat tire me on my way to lab last week, gifting the tendons in my lower body a break from straining across town in the hot soup that is summer air in Philadelphia until I can go get the stuff to mend it.
I can’t say the same for the tendons in my wrists though. I’ve been hard at work developing some exciting stories for you all, and I can’t wait to share them with you! Here’s a bit of a teaser of what’s going to be published next: Scientists are leveraging the talents of some of Earth’s tiniest creatures to make some of the most innovative biomaterials—all with HUGE implications for how we manufacture biotechnologies more sustainably. Think you know who these organisms may be? Feel free to leave any guesses in the comments!
New and Interesting Publications
Here’s a juicy, well-designed, and excellently written paper for all you rotator cuff enthusiasts! If you read one paper all month, this should probably be the one!
The authors tested an extracellular matrix (ECM)-derived scaffold made from “minimally-processed” umbilical cord tissue. They hoped these scaffolds would successfully guide tendon-to-bone healing in patients with rotator cuff injuries and reduce retearing after repair. In vitro, these scaffolds—which retained many of their umbilical cord cells and ECM components—favorably increased angiogenesis in HUVECs, increased M2 polarization in RAW264.7 macrophages, and drove the deposition of chondrogenic proteins in pellets made from human bone-marrow-derived mesenchymal stromal cells.
The research team then went on to conduct a study in dogs with acute rotator cuff injuries (n = 12); after two years of follow up, their scaffolds healed the tendon-to-bone interface more successfully than standard surgical repair did. But the researchers didn’t stop there! They also conducted a two year clinical study in 20 people with rotator cuff injuries (n = 10). Compared to the gold-standard of care, the umbilical-cord-derived scaffolds more successfully healed the rotator cuff tears and minimized repeat injury as measured by MRI.
Use of autologous mesenchymal stromal cell injections to treat Achilles tendinopathy reduced patient pain in Phase IIA study
Researchers in the UK recently completed a “first in man study to assess the safety and efficacy of autologous MSC injection” in 10 human patients with “non-insertional Achilles tendinopathy.” They followed the patients for two years, during which time no adverse events were recorded. Patients also experienced significant reductions in pain over that time. Check out the full write up to see all their data. I really enjoyed their detailed yet brief discussion.
Skeletal Stem Cells were more effective than Mesenchymal Stromal Cells at healing supraspinatus tendon injury in mice
This summer’s love for the rotator cuff continues. Recently, I’ve been exploring in great detail how the sourcing and use of different cell types may impact the efficacy of intervertebral disc therapies, so this article really piqued my interest.
In this study, murine Skeletal Stem Cells (SSCs) were more chondrogenic, more osteogenic, and less adipogenic than murine Mesenchymal Stromal Cells (MSCs) in vitro. In a very large mouse study (n = 56), the authors also found that SSCs more successfully repaired the tendon-to-bone interface in acute rotator cuff injuries. I was particularly impressed by the results of their biomechanical testing. Not only did the SSCs drive the deposition of a healthier-looking enthesis, but the remodeled tissue was also stronger, performing more like an uninjured control, than the MSC-treated injury.
Some of you might be asking, as did I—what’s the real difference between a Mesenchymal Stromal Cell (MSC) and a Skeletal Stem Cell (SSC)? Well, dear reader, according to a more in depth review, it seems that SSCs and MSCs are similar in that they both originate from the mesenchyme, but they have unique surface markers that make them distinct. The review semi-helpfully defines SSCs as a “more homogeneous subpopulation of MSCs.” Where MSCs can be isolated from many tissues of mesenchymal origin, SSCs can only be found in the skeleton. In today’s study, the MSCs were isolated from the bone marrow whereas the SSCs were isolated directly from calcified bone of tibias and femurs. The authors detail some helpful discussion on page 93 to drive home the distinction between stem cells of mesenchymal origin.
A cost-effective and sustainable tissue source for corneal transplantations: Decellularized sheep corneas from stored slaughterhouse waste
Yes, you read that correctly. Sheep corneas. From the slaughterhouse. For people. Tissue for corneal transplantation is typically sourced from human donors, and over 13 million people at any given moment await donor corneas. I like this paper not because it’s an elaborate study but because it asks a really powerful, resourceful question: How can we take something that’s currently a waste product—a cornea from slaughtered sheep— and sustainably transform it to satisfy a pressing medical need? Although there is clearly still a lot of work to be done here, I encourage you to look over the paper to better understand the nuance of this project.
“Sustainable biomaterials: Electrospun polycaprolactone fibers enriched with freshwater snail calcium carbonate and waste human hair keratin”
Last but not least, another trash to treasure story. They’ll really make biomaterials out of anything (and when I say they, I mean all of us). This research team functionalized electrospun polycaprolactone (PCL) scaffolds using keratin—and its associated LDV/RGD cell adhesion motifs—purified from human hair as well as calcium carbonate made from snail shells. The authors expound on the benefits of these natural materials over more traditional synthetic alternatives and their potential in bone tissue engineering in the paper’s introduction. So keep your eyes open, people—you never know from where the next material innovation may come.
Until next time,
Matthew
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