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How to Repair Human Bones

Combining cutting-edge biology and engineering to make new human-like bones a reality

Image by Mathew Schwartz on Unsplash

We often think of our bones as the ultimate unbreakable entity—the steel of the body. Unfortunately, this is far from the truth.

Hundreds of thousands of people experience fracture nonunions each year—where their bones do not heal properly from a fracture after the expected amount of time. Hundreds of thousands of others receive spinal fusions where some of their vertebrae are fused together to help with bone deformities and pain.

One way of treating nonunions and achieving spinal fusion is by regenerating bones. As futuristic as this sounds, it’s a procedure that’s been done many times over the past two decades.

The Regrowth Sponge: Current Approaches

Bone regeneration usually involves a protein called bone morphogenetic protein-2 (BMP-2) and a material called a collagen sponge. Before you click away because of these seemingly incomprehensible terms, let me explain.

BMP-2 is part of a family of proteins called bone morphogenetic proteins (BMPs); BMPs primarily induce bone formation but can inhibit it too both during embryonic development and bone repair in adults.

Specifically, BMP-2 induces bone formation and without it, mice die during embryonic development. It makes sense, then, that BMP-2 can be used to repair bones by promoting new bone growth. Unfortunately, bone repair isn’t as simple as adding some extra BMP-2 to our desired area.

This is where the collagen sponge comes in. Without the sponge, BMP-2 isn’t retained at our desired site for a long time; this is the opposite of what we want.

But what are collagen sponges? They’re porous sponges made of collagen—no surprises there. You may know collagen as a protein essential to youthful skin but it also plays an integral role in maintaining hair, bones, and connective tissues in general.

Image by author. BMP-2 from the collagen sponge coerces unspecialized cells to become cells that form bones, thereby inducing bone formation.

In this case, collagen sponges are fantastic because collagen is naturally found in bones and interacts well with cells and other bodily materials. When performing procedures like repairing fracture nonunions and spinal fusions, physicians soak the collagen sponge in a protein solution including BMP-2. They then place the protein-soaked collagen sponge on or in the desired site.

The purpose of the sponge is two-fold:

  1. Effectively and efficiently transport BMP-2 to the desired site
  2. Act as a scaffold—or a support-providing structure—which allows for new bone growth

While this process is fascinating and very useful, it isn’t always effective. For one, collagen sponges don’t have a particularly strong affinity towards BMP-2; this means BMP-2 may not bind or attach as well as other materials to the sponges, causing unintended effects.

Recent studies have suggested new reasons for leaving collagen sponges behind: one 2019 study found that when these sponges were used without BMP-2, they negatively impacted bone regeneration when in fact, their effect should have been neutral.

The New Star of the Show: A Different Approach

But don’t lose hope just yet. A new study published in Science by Hettiaratchi et al. suggests a new approach to make bone regeneration much more effective. The paper presents a special sugar molecule called heparin as the star of the show, instead of the collagen sponge.

Previously, scientists have found that heparin can enhance bone regeneration by improving the specialization of cells that form bones (as shown in the earlier diagram). Think of heparin as a booster seat—some children still use them when no longer required by law because though it isn’t necessary, it improves their experience in the car.

Heparin (represented by a green square) is holding BMP-2 (represented by a blue circle) up so that BMP-2 can see out of the car window (like a booster seat). A speech bubble pointing at heparin says “Can you see out of the window?”
Image by author. Heparin “boosting” BMP-2!

The paper by Hettiaratchi et al. actually finds that the heparin booster seat may be necessary despite what the law of regenerative medicine used to say since it improves bone regeneration. Let’s take a look at how.

In addition to improving the specialization of bone-forming cells, heparin also has a strong affinity for BMP-2. I’ll let Dr. Hettiaratchi explain what this means:

Affinity-based biomaterials involve “[engineering] our materials to bind specifically yet reversibly to a number of different proteins of interest.”

Hettiaratchi et al. have developed new microparticles—particles about the width of a strand of hair—that can bind to several times more BMP-2 molecules compared to previous biomaterials.

As well, scientists found that more of the BMP-2 would remain in the desired location when heparin microparticles were used; this is due to a property we’ve already discussed: heparin’s strong affinity for BMP-2. This is critical because:

  1. It prevents a bone formation-inducing protein from traveling to areas where we don’t need increased bone formation.
  2. More of the BMP-2 is retained where it’s meant to be meaning more robust bone formation can take place.

On top of that when using the microparticles, the regenerated bones were just as strong as those regenerated using collagen sponges, despite the lack of unnecessary extra bone growth that’s seen using a collagen sponge.

These results are incredibly promising to say the least. But research is ongoing and more tests are needed before heparin microparticles enter humans. For instance, heparin is also an anticoagulant, meaning it can decrease blood clotting. There may be some side effects caused by this ability that should be explored thoroughly.

But Do We Really Need This?

Some may think that these bone regeneration efforts aren’t needed at all. After all, if we have technologies such as metal, plastic, and ceramic joint replacements, why do we need this biological and more complex approach?

Images by Lena, modified by author. Example of knee joint replacement.

The goal isn’t necessarily to replace one approach with the other but to have a complementary relationship, explains Dr. Hettiaratchi. For instance, currently, joint replacements don’t last a lifetime: they are usually effective for 10 to 15 years before causing issues and requiring replacement or further attention.

Using biological approaches that help better integrate these replacements into the body will likely increase how long replacements last and improve patients’ lives.

All in all, the field of bone regeneration has an extremely bright future. Combining what we now know about biomaterials and proteins like BMP-2, we will soon be able to more effectively regrow bones where needed. Combined with the power of technology and engineering being used in traditional joint and bone replacements, treating issues like fracture nonunions may become small inconveniences rather than lengthy processes.

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Parmin Sedigh

Parmin Sedigh

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Science communicator trying to learn something new everyday | Published in Start It Up, Predict & The Writing Cooperative