Highlights: 

  • Peptide-blood gels recreate the regenerative hematoma (RH) microenvironment, promoting cell recruitment and controlled growth factor release to accelerate healing and regeneration.
  • Peptide-blood gels enhance bone regeneration and reduce markers of inflammation. 

Whether you pull a muscle, stub a toe, or break a bone, the body activates efficient healing mechanisms to restore tissue integrity, reduce inflammation, and rebuild damaged structures. For major injuries, the body kickstarts the healing process by using liquid blood to form a regenerative hematoma (RH) – an enriched matrix containing a milieu of functional biomolecules that stimulate healing and regeneration. Notably, increasing evidence suggests we can manipulate the RH microenvironment to enhance its regenerative potential, making it a primary target for regenerative therapeutics. 

Now, in a study published in Advanced Materials, researchers from the University of Nottingham engineered a biomaterial that replicates the properties of the RH using a combination of blood and peptide amphiphiles (PAs) – synthetic molecules that form nanostructures. This gel-like material not only mimics the compositional and functional properties of the natural hematoma but also enhances its ability to heal tissue.

Peptide-Blood Gels Recruit and Release Healing Molecules 

The peptide-blood gel recreates the dynamic microenvironment of the RH by preserving key blood components and regulating the release of critical growth factors. When PAs were mixed with blood, they co-assembled with fibrin and other blood proteins to form a stable hydrogel. Results showed that this material stored and gradually released biomolecules like VEGF, TGF-β, and PDGF, demonstrating that the gel successfully replicates the natural RH response.  

Moreover, laboratory tests revealed that the gel attracted and supported the growth of mesenchymal stromal cells, endothelial cells, and fibroblasts – cell types that modulate critical healing mechanisms. Uniquely, the cells adhered to and migrated into the gel, closely mimicking how natural RH promotes cell recruitment. 

More importantly, the research team noted that the gels released growth factors in a controlled and sustained manner, ensuring a consistent supply of signals essential for regeneration. This prolonged-release contrasts with the rapid depletion seen in natural clots, enhancing the gel’s ability to support processes like angiogenesis, matrix deposition, and cell proliferation over an extended period. Collectively, these findings highlight the gel’s potential to mimic and surpass the regenerative capacity of the natural hematoma. 

Peptide-Blood Gels Enhance Bone Regeneration 

To assess its ability to repair severe injuries, the researchers tested the gel in a critical-sized cranial defect in rats – a bone injury that would not heal on its own. Using each rat’s blood, they created personalized hydrogels and implanted them into the bone defect. After six weeks, the gel significantly improved bone formation, with new tissue filling the defect and resembling healthy bone.

Compared to untreated controls, the gel-treated injuries showed greater bone density and organization. Remarkably, the gel’s performance was comparable to a commercial bone substitute, but with the added advantages of simplicity and personalization. Notably, treated rats exhibited lower levels of inflammatory markers (TNF-α, IL-1β), indicating reduced inflammation and a more favorable environment for healing and bone regeneration. 

(Mata et al., 2024 | Advanced Materials) Peptide-blood gels improve bone healing. Compared to untreated rats (top row), those treated with peptide blood gels (bottom two rows) exhibit greater bone formation. 

A Breakthrough In Regenerative Medicine 

Overall, the study’s findings demonstrate that peptide-blood gels could make a huge impact in the field of regenerative medicine. The personalized nature of the gel, made from a patient’s own blood, minimizes the risk of rejection and makes the technology accessible. Moreover, its adaptability allows for precise 3D printing into customizable shapes and structures, facilitating customized solutions for targeted injuries or specific therapeutic applications.

“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,” explains Dr. Cosimo Ligorio, the study’s co-author. “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 tunable regenerative implants.”