Innovative regenerative therapy solutions for bone regeneration - cmRNAbone

Bone diseases impact hundreds of millions of people worldwide every year. It is often overlooked that bone is the second most transplanted biological material after blood and bone marrow. As older people stay more active, it is not unusual to see 70-year old skiers, the need for regenerative bone solutions is increasing.

cmRNAbone is bringing innovative regenerative therapy solutions for bone regeneration. It's combining different fields like nanotechnology, 3D printing, cmRNA technology and calcium phosphates and putting them all together to come up with a custom patient specific scaffold for bone regeneration.

With the cmRNAbone project, the main objective we have is to develop a translational technology where you could have a material delivery system which would provide cells with stimulatory molecules, which would then lead to new bone formation.

Bone fractures normally heal quite well. But if you have a large bone defect, it cannot heal by itself, and you can end up with a non-union, which is when the bone doesn't bridge. We are trying to help the bone promote this regeneration by making a composite of uronic acids and calcium phosphate particles, combine it with chemically modified RNA from the cmRNAbone project, and then we hope that those components together induce bone regeneration which will bridge the gap of the bone.

One of the key aspects of this project was figuring out how to make it clinically translatable. You need to come up with a system which could actually be used in a hospital, in a patient. For that it would need to be financially viable. How do you deliver these therapies? How do you make the cells work? How do you make the cells behave in the way you want them to behave? You need the material science aspects. So you need to have a delivery carrier system, a gel, which potentially could be 3D printed. How would you develop those 3D printing technologies?

The cmRNAbone 3D bioprinters, developed specifically with clinical translation in mind, were developed by our consortium partner IDONIAL in Asturias, Spain. They are similar to other 3D printers, but for this printer, the cartridge, which looks similar to a syringe, is filled with the composite which has a base of uronic acid with calcium phosphate. The syringe has a plunger at the top, different needle sizes can be attached at the bottom. While the plunger is being pressed down, the material gets extruded. Meanwhile the platform underneath is moving in a specific path that we defined before. And that is how it creates the specific structure that we need. The printer also has a light source in order to cure the composite so that you can pick it up and put it in water or cell culture media and it stays stable.

Of course, the program is a discovery program, based on developing novel technologies that may eventually be developed into a treatment for patients, so there is no expectation for immediate results. However, I think what is particularly exciting from a therapeutic point of view, is that these hydrogels are biologically functional. So, they contain the right stimuli to instruct the cells of the body to actually make vessels, bone and nerves in a coordinated way. This makes it particularly applicable because it can be shaped in any way you want, so aside from making bone for a traumatic injury, if you have a regenerative disease where the bone itself, like in osteoporosis, has less density, you can definitely imagine that this gel can provide the stimuli for regenerating more bone mass.

This consortium was the first to really demonstrate the potential of this technology beyond vaccination. We know that chemically modified RNA is very potent for vaccination, we have seen that clearly during the COVID vaccination period. However, we are now able to demonstrate that chemically modified RNA has a potential for tissue regeneration as well. With cmRNAbone, we have been able to prove these molecules can induce regeneration of different tissues and different processes.

It is very attractive that messenger RNA technologies can make regenerative therapies affordable where traditional gene therapy using vital delivery of plasmid DNAs is often cost prohibitive. We have seen products being removed from the market just because they are not affordable for the healthcare system and messenger RNA can be a complete game-changer for those situations. We can make this technology affordable, available for anyone in the healthcare system who needs it. It is efficient. It works, it has high tolerability.

So now we're providing data to the scientific field, which really does show that a very small initial dose can have a long term sustained effect. And the nice thing about the whole concept is it doesn't need anything from the patient. The gel, the material, the coding sequence, the molecules: we can make all of it in the labs.

So we truly think this is a technology that came to stay.