A new implant embedded with growth factors may help heal major bone injuries.
Major damage to bones can be very difficult to repair – especially injuries of the face or the spine. There must be enough bone left on either side of the break to use traditional implants like plates and screws. If a lot of bone is missing, doctors will try to transplant bone taken from somewhere else in the patient’s body. This obviously causes a second injury site, and the implant doesn’t always work.
The recent boom in 3D printing has given a lot of hope for this field. It is now possible to make implants that are anatomically perfect for each patient. Scientists have even gone so far as to seed cells onto these implants to turn them into living tissue. Until now, each implant must be specifically made for each patient which is expensive and time consuming.
Paula Hammond and her team from MIT took a different approach. Instead of seeding cells onto the implant, they seeded growth factors that would stimulate surrounding tissues to make bone.In this way they hoped to make a product that would work in many different types of injuries.
Growth factors are molecules that the body secretes to tell cells and tissues to grow. Osteoblasts are the cells that make bone. They release and respond the a number of different growth factors including bone morphogenetic protein-2 (BMP-2) and platelet-derived growth factor-BB (PDGF-BB).
Dr Hammond’s group embedded these two growth factors into a special film, called a polyelectrolyte multilayer (PEM) film. This film is made up of multiple extremely thin layers (nanolayers) with different charges (positive or negative). It can be designed to degrade and release the growth factors at a specific rate. Each layer could contain a different cocktail of growth factors or other signalling molecules. In this study, the PDGF-BB was embedded in the outer layers so was released quickly, whereas the BMP-2 was in the inner layers and released more slowly. The PEM film can be put over many different types of implants – metal, degradable plastics, other biomaterials. Dr Hammond chose to put it on a porous biodegradable membrane. Once the PEM covered membrane is implanted in the body, it should tell the patient’s own body to make bone and repair the injury. Newly formed bone should replace the implant as it degrades.
The body’s own processes can be disrupted by a major injury. There needs to be enough surrounding healthy tissue left to provide the signals for healing to occur. If there isn’t enough, then the signals need to be given externally. If growth factors are given all at once, such as in an injection, the tissue only uses a small amount and clears away the rest. So Dr Hammond and her team aimed to find a way to give controlled delivery of these growth factors over time.
To test whether this worked, the scientists implanted coated membranes into rats that had skull wounds. They used dyes to measure how much of the growth factors was released. PDGF-BB was released for first 11 days and BMP-2 was released for 20 days. Both were released gradually, not in bursts.
Rats with no implant had no bone healing. Rats implanted with uncoated membrane implant formed scar tissue at the wound edges and only grew small pieces of bone that didn’t fuse with the skull surrounding wound. This tissue was not stiff and did not resist compression. Rats with the coated membrane quickly formed new bone at the wound edges which filled in bone deficit. Bone grew faster and formed more blood vessels when both growth factors were in the implant than when there was only BMP. The bone that grew around the double growth factor implants was as dense, stiff and resistant to compression as normal bone.
This is a really exciting tool that can be used to study what the optimal timing and rate of release of growth factors is. Also which combination of growth factors works best. The body uses a whole symphony of signals to orchestrate tissue repair and regeneration. It is a tall order to try and replicate that in an implant.