by Justin Jackson , Medical Xpress

Vision and rationale of the study. a) Main biological events and factors involved in the formation of a regenerative/hematoma clot (RH). b) Vision of the workflow from whole blood to personalized, 3D printed biocooperative implants. c,d) Schematic representation of supramolecular co-assembly of PA molecules with blood components to fabricate PA-blood hydrogels. Inset shows the capability of glutamine-displaying PA molecules to interact with fibrin through Factor XIIIa. e) Schematics of fibrin glutamine-lysine cross-linking mediated by Factor XIIIa. Credit: Advanced Materials (2024). DOI: 10.1002/adma.202407156

Researchers from Queen Mary University of London and the University of Nottingham have developed a biocooperative material that harnesses blood clotting and peptide self-assembly to engineer personalized regenerative implants for healing severe wounds and fractures.

Advancements in scientific knowledge, assisted by new technological tools, have placed effective regenerative therapies tantalizingly within reach of clinical therapeutics. Replicating the body's complex healing environment remains a significant challenge.

Promising approaches often rely on stem cells, biomimetic materials, or allogeneic grafts, each with its own obstacles to becoming successful and reliable treatment options.

Most body tissues have evolved to heal minor injuries efficiently, largely relying on forming a regenerative hematoma in a dynamic environment that coordinates molecular and cellular processes for complete repair.

In a study, "Biocooperative Regenerative Materials by Harnessing Blood-Clotting and Peptide Self-Assembly," published in Advanced Materials, researchers designed peptide amphiphiles (PAs) to interact with blood components during coagulation, creating a living material that mimics the regenerative hematoma (RH).

By co-assembling PAs with a patient's own blood components, they engineered hydrogels exhibiting key compositional and structural properties of the RH. The PAs were designed with different charge densities to interact with proteins such as fibrinogen and albumin.

Incorporating glutamine residues into the PAs allowed the enzyme Factor XIIIa to cross-link PAs with fibrin, enhancing the material's mechanical properties.

Mechanical testing showed a tunable stiffness, and analysis confirmed a robust network structure. Scanning electron microscopy revealed a composite nanofibrous architecture resembling natural clots, with platelets adhering and spreading normally.

The material preserved normal platelet behavior, generated a continuous source of growth factors, and supported the growth of mesenchymal stromal cells, endothelial cells, and fibroblasts in vitro.

Demonstrating compatibility with 3D printing techniques, the researchers enabled the fabrication of personalized implants with precise geometries at the point of use.

In vivo studies using a rat skull defect model showed that the PA-blood gel implants promoted bone regeneration. The experiment with two formulations of the gel demonstrated 62% and 56% new bone formation, respectively, compared to 50% for the commercially available Bio-Oss and 30% for untreated defects, indicating the material's potential in clinical applications.

By harnessing complex mechanisms that nature already uses to heal, this biocooperative strategy takes advantage of a billion years of evolutionary trial and error in developing a new regenerative method.

While challenges remain in translating this approach to human medicine, the study represents a big step toward accessible, personalized regenerative healing therapies.

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

Journal information: Advanced Materials 

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