When you get a cut or fracture, your body springs into action, turning liquid blood into a solid clot that stops bleeding and kickstarts the healing process. This clot, called a regenerative hematoma (RH), is packed with cells and proteins that orchestrate the repair of tissues. The initial formation of the RH is critical — it provides a scaffold where cells can gather, promoting the formation of new tissue and blood vessels.

Soraya Padilla-Lopategui and her team at Queen Mary University of London and the University of Nottingham wanted to use this mechanism. Basically, they developed a way to use a patient’s own blood to repair their broken bones.

Using the body’s defenses

Our bodies are naturally equipped to repair minor injuries through a sophisticated process involving the regenerative hematoma. And it’s not just us. Many mammals have similar mechanisms too, the key is to be able to replicate it in a controlled fashion.

The crux of this breakthrough lies in the use of peptide amphiphiles (PAs) — molecules that can self-assemble into nanofibers and interact with blood proteins to create biocompatible gels. By blending these PAs with blood, the researchers were able to engineer a material that not only mimics the natural RH but also enhances its properties.

Essentially these PAs self-assemble when mixed with blood. They form a 3D network that incorporates essential proteins, platelets, and growth factors from the blood. Thus, it creates a scaffold that closely resembles natural RH. This structure provides a constant source of growth factors like vascular endothelial growth factor and platelet-derived growth factor, which are vital for cellular growth and healing.

“For years, scientists have been looking at synthetic approaches to recreate the natural regenerative environment, which has proven difficult given its inherent complexity. Here, we have taken an approach to try to work with biology instead of recreating it. This “biocooperative” approach opens opportunities to develop regenerative materials by harnessing and enhancing mechanisms of the natural healing process. In other words, our approach aims to use regenerative mechanisms that we have evolved with as fabrication steps to engineer regenerative materials,” says Alvaro Mata, Professor in Biomedical Engineering and Biomaterials in Nottingham University.

Personalized inputs

To make the technology even more exciting, you can tweak and personalize parts of it based on your own body.

Because the material uses the patient’s own blood, it reduces the risk of immune rejection and simplifies the process of creating individualized implants. By using whole blood, the team bypasses the need for complex processing steps often required with synthetic materials, making this approach more viable for clinical use.

“The possibility to easily and safely turn people’s blood into highly regenerative implants is really exciting. Blood is practically free and can be easily obtained from patients in relatively high volumes. Our aim is to establish a toolkit that could be easily accessed and used within a clinical setting to rapidly and safely transform patients’ blood into rich, accessible, and tuneable regenerative implants,” added co-author Cosimo Ligorio, from the Faculty of Engineering at Nottingham University.

The researchers started in lab studies, converting blood samples into biocooperative gels that could be customized in terms of shape and structure through 3D printing. They controlled the speed and pressure of this 3D printing, crafting specific shapes with robust mechanical properties. The experiment with two formulations of the gel demonstrated 62% and 56% new bone formation, respectively, compared to 50% for the commercially available solutions and 30% for untreated defects, indicating the material’s potential in clinical applications.

Although the study was only carried out on rat cells, the researchers are confident a similar approach can be used on humans as well.

The ability to tune the material’s properties opens doors to applications in areas where precise mechanical and biological properties are essential. The team envisions future studies to optimize the PA-blood gel for specific types of injuries, with a focus on integrating other types of cells or molecules that promote healing.

Furthermore, while this study focused primarily on bone healing, the PA-blood technology holds potential for a broad range of applications. For instance, the gel could be used as a hemostatic agent, rapidly forming clots in response to bleeding, which would be especially useful for patients with clotting disorders. Moreover, the method could be adapted for other tissues such as skin or nerves, which have their own unique regenerative requirements.

A few challenges remain

Despite its promise, several challenges remain before the PA-blood gel can be widely adopted in clinical settings. For instance, the variability in blood composition between individuals may affect the material’s performance. Also, it’s not fully clear how well the findings would translate to human cells

Another challenge lies in scaling up production of these personalized materials. While the 3D printing approach shows promise for creating customized shapes, the feasibility of integrating this technology into standard clinical workflows will need further exploration. The development of user-friendly devices that allow clinicians to create these implants directly from patient blood samples could streamline the process, making it more accessible to a wider range of healthcare facilities.

The study provides promising insights. It remains preclinical, and further research is needed to explore its applicability in human medicine. However, the researchers found that their approach can achieve reproducible results across different blood samples.

The potential applications of this technology are vast, ranging from surgical implants to trauma care. As research continues, this PA-blood technology could serve as a foundation for other regenerative solutions, providing new hope for patients who need accessible, effective, and personalized therapies.

Journal Reference: Soraya Padilla‐Lopategui et al, Biocooperative Regenerative Materials by Harnessing Blood‐Clotting and Peptide Self‐Assembly, Advanced Materials (2024). DOI: 10.1002/adma.202407156