‘Therapeutic Blood Clots’ Could Remedy Cartilage Loss from Osteoarthritis

By Deborah Borfitz

March 13, 2025 | Scientists at the University of Wisconsin – Madison believe it could soon be possible to use people’s own blood clots to treat bone-on-bone osteoarthritis by having the material be the scaffolding that fills the space where cushioning cartilage used to be. The plan is to have the clots serve as a temporary matrix that cells will infiltrate to be exposed to a gene that encourages them to form hyaline cartilage, according to William Murphy, Ph.D., a professor of biomedical engineering and orthopedics and rehabilitation. 

These “therapeutic blood clots” are activated by messenger RNA (mRNA) that gets delivered by mineral-coated microparticles that encode for the production of transforming growth factor beta-1 (TGF-β1), a protein that supports cartilage formation, he explains. The clots get placed, like a puzzle piece, into defects in the cartilage of a corresponding size and shape. Details of the novel approach are described in an article that was published recently in Bioactive Materials (DOI: 10.1016/j.bioactmat.2024.11.033). 

Although the initial focus is on the knee, the approach could be broadly applied to other key joints like the hips and shoulders, says Murphy. It could also be an alternative to multiple other strategies in use and under development that use foreign rather than patient-derived materials providing a support structure for cartilage formation. 

Here, researchers are using clot materials that would form normally in the body and are meant to be temporary. Infiltrating cells eventually degrade that material and form their own matrix, with the type of tissue formed being dictated in part by the gene that gets delivered to those cells, Murphy says. 

Local delivery of mRNA-activated TGF-β1 was successfully demonstrated in rabbit models, and plans are to move into sheep models over the coming six months. Murphy and his team hope to launch a first-in-human trial in another few years and, if all goes well, bring to market an implantable or injectable treatment as an alternative to steroid or hyaluronic acid shots, minimally invasive arthroscopic chondroplasty, or joint replacement surgery. 

‘Ubiquitous Problem’

Better treatments for osteoarthritis represent a massive opportunity because so many people suffer from the painful and debilitating chronic joint disease, says Murphy, who has endured two hip replacement surgeries himself. “This is almost a ubiquitous problem in people over 40 years old, whether it is diagnosed or not.” 

The Centers for Disease Control and Prevention reports that osteoarthritis is the most common form of arthritis, affecting roughly 33 million adults in the United States. The knee was a good starting point for Murphy and his team both because there are many mature animal models for the research and the joint is associated with the most clinical problems, he says. 

For purposes of reducing the pain and disability associated with osteoarthritis, it’s critical to fill the gap between two bones, he continues. But oftentimes, if cartilage is coaxed to form around a scaffolding material, it is fibrocartilage more like what is in the ear or nose than what is ideal for a joint subject to a lot of compression and lateral movement. 

The problem is that cartilage repair surgery commonly uses a synthetic, space-filling structure that cells climb into to create new tissue. The material is usually hydrogel, networks of synthetic polymers that are 90% water. The material that forms therapeutic clots is also a hydrogel, but the polymers are all natural, points out Murphy.  

Arthroscopic chondroplasty, a minimally invasive surgery sometimes done in lieu of cartilage repair and regeneration surgery or a total joint replacement, can offer pain relief but sometimes only for a few weeks, says Murphy. The procedure involves drilling a couple of holes into the underlying bone to stimulate the growth of new cartilage tissue. Abrasion chondroplasty is typically done whereby exposed bone is scraped until it bleeds. Alternatively, damaged cartilage is sometimes treated via a microfracture surgery where the subchondral bone that sits below the cartilage is intentionally fractured to get it to bleed and thereby bring in the cells and molecules that promote the formation of fibrous, scar-like tissue, he says. 

While cortisone injections can be helpful in reducing inflammation and thereby relieving pain, possibly allowing someone to engage in physical therapy, the effects are temporary and somewhat unpredictable and in severe cases may not be effective, Murphy says. “Long term, it’s also not the best thing for your joint to have steroids floating around,” he adds, as it can slow or even damage healing. 

Engineering Clots

Murphy’s group made their initial foray into tissue engineering for the healing of large bone defects, and one of their first technologies was 3D-printed synthetic scaffold to support long bone reconstruction. Synthetic materials made sense in this context because a more extensive scaffold is required for bone than for cartilage, and the materials must be mechanically robust, he says. 

When cartilage is developing in humans, TGF-β1 encourages stem cells to become cartilage-forming cells that produce cartilage tissue, says Murphy. If that signal isn’t present or TGF-β1 is present at the wrong concentration it results in improper cartilage formation. “So, we decided to turn that signal on in the adult to see whether... [it] would lead to cartilage formation like it does during tissue development.”  

To that end, Murphy and his team extracted cells from bone marrow aspirate, a subset of which are stem cells that can form bone cartilage, which were then mixed with peripheral blood. This provided the right conditions for the formation of the clots when combined into an aqueous solution with the dust-like microparticles. The mineral particles and cells from the bone marrow are “together in three dimensions” within those clots.   

The therapeutics blood clots have thus far been surgically implanted into animals and could one day serve as the graft in standard arthroscopic procedures to fill the defect space, says Murphy, but they could also potentially be injected. “The idea of forming these clots and having them exist in a syringe and directly injected to the site of interest would allow this to be done in a much more minimally invasive way,” he notes. The chief challenge with the syringe delivery route would be preventing cell damage. 

“Our hope is to make this process more analogous to what happens when hyaluronic acid is injected into a joint,” he says. Hyaluronic acid is another naturally derived material that is safe and used quite often in patients with severe osteoarthritis but without demonstrated effectiveness.  

Muscles and Bones

If the large animal studies are successfully completed, the next step would be to do a detailed safety-tox evaluation of the materials and then schedule an initial meeting with the U.S. Food and Drug Administration to talk about the path forward toward a first-in-human trial, says Murphy. Once that meeting is scheduled, it will still be at least a couple of years before the initial clinical study would launch.  

Murphy and his colleagues have ongoing studies looking at using a similar process for skeletal muscle regeneration where the problem is local muscle atrophy. He reports that a series of yet-unpublished studies in rodents has shown “significant success” in terms of new skeletal muscle tissue formation in large defects by turning on a signal that influences skeletal muscle development. It would likely not be appropriate for muscle wasting due to a systemic disease, because lighting up the signal throughout the entire body could have “all kinds of unintended consequences.” 

It’s a bit simpler on the bone side, Murphy says, because the signals from the biomaterial clots used to generate tissue—bone morphogenetic proteins (BMPs)—are a clinical product used over the past two decades for treating large bone defects. Here, the intent is to deliver new, more powerful versions of BMPs to stimulate bone regeneration, which is “an area that’s a little more crowded with other approaches.”