Prosthetic implants are some of the most widely used medical devices with applications in fields like dentistry and orthopedics; however, the development of new implants with increased compatibility is suboptimal, thus contributing to worse clinical outcomes. One contributing factor is the lack of appropriate models that can show osseointegration, the process in which the implant blends together with the native bone. To overcome this, the researchers present a novel engineered bone platform made of a decellularized bone scaffold and stem cells. Using this platform, they are able to test the osseointegration potential of titanium and stainless steel implants by comparing the mechanical and biological properties of each platform. 

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What did these researchers do?

In this study, researchers tested the osseointegration potential of titanium versus stainless steel implants in their engineered bone platform. They did this by first testing the mechanical bond between the tissue and the implant, which shows the primary stability immediately after implantation. Using a method called pullout testing, they demonstrated that titanium was able to form a much stronger bond than stainless steel as it was able to withstand a much larger pulling force before becoming loosened. Then, they tested the biological bond that forms between the tissue and implant over a longer period of time. Using various assays, they demonstrated that the titanium implant showed better bone formation and was able to anchor directly to the bone compared to the stainless steel implant that was not able to do this. From these data, the researchers concluded that the titanium implant was more suitable for prosthetic implants as it provided greater mechanical and biological stability in the engineered bone platform. 

 

Why is this important?

Although great progress has been made in the development of prosthetic implants, there are still many aspects that can be improved, such as developing biomaterials that are more compatible with humans or optimizing current designs to promote more efficient bone regeneration. Unfortunately, current tissue-implant models suffer from many limitations that make it difficult to address these needs. For example, the most common models are 2D cell culture models and animals. Since cell models are two-dimensional, they cannot capture the 3D architecture of the implant-tissue system, nor can they be used to test mechanical properties like how much weight they can bear. While animal models address some of these needs, they are expensive, time-consuming, and may not always demonstrate relevance in humans.

 

A biomimetic engineered bone platform, as the researchers describe, can address many of these concerns. It is relatively cheap and can provide patient-specific insights. Furthermore, it can test the osseointegration potential of various types of implants in an in vitro setting, thus lessening the need for invasive procedures in patients or animals. ​

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How did the researchers do this?

Researchers first inserted either titanium or stainless steel screw-shaped implants into a decellularized bone scaffold. Then, they created a 3D model of osseointegration by seeding these bone scaffolds with induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs). iMSCs are important to the osseointegration process as they can differentiate into bone cells, thereby making a stronger bond between the implant and the tissue. Furthermore, iMSCs can be derived from patient stem cells, thus also providing the possibility of a patient-specific model. They had two major timepoints at which they assessed the osseointegration properties of these implants: right before iMSC seeding and after 7 weeks of iMSC seeding. 

 

To test the mechanical bond between the implant and tissue, the researchers used pullout testing in which they attached their implant-bone model to a clamp and then assessed the amount of force required to pull out the implant screw. They found that at the initial time point, there was no difference between the amount of force required to pull out the titanium implant versus the stainless steel implant. However, at 7 weeks post-iMSC seeding, they found that the titanium implant required significantly more force to be removed compared to the stainless steel implant. 

 

To test the biological bond between the implant and tissue, the researchers use several assays to determine which implant resulted in better osseointegration. They used bone mineralization and formation as an indicator of increased bone formation that leads to a stronger bond between the implant and bone tissue. By quantifying the activity of certain bone-associated markers like alkaline phosphatase and RUNX2, they determined that the titanium implant had increased levels of each of these at the 7-week time point. They were also able to visualize increased bone mineralization, such as more calcium deposits, in the titanium implant platform. Overall, the researchers concluded that titanium implant is better for osseointegration in terms of both mechanical and biological bonds than the stainless steel implant.