Unlock Your Graft's Potential: The Impact of Growth Factors and Proteins on Bone Grafts

Under the right conditions, healthy bone tissue has the ability to fully regenerate. However, complete healing is often hindered by various factors, including the size of the defect and patient-specific comorbidities. To address these challenges, bone grafts are frequently used to treat defects and significant bone loss.

Bone grafts are the second most common tissue transplant in the United States, with allografts often used to stimulate bone growth in various medical procedures. Despite this, the occurrence of non-union post-treatment is approximately 10%, which has led to a growing demand for enhanced osteoconductive and osteoinductive products for bone tissue regeneration.¹

Growth factors and proteins are key players in the bone repair process, enhancing the osteoinductive potential of bone grafts by recruiting and differentiating mesenchymal stem cells (MSCs).¹ In certain cases, adding growth factors and proteins to allografts can further support tissue healing and optimize outcomes.

How Do They Work?

Proteins are essential components of bone, comprising about half of its volume and one-third of its mass. When a bone is fractured, the body requires protein to generate new bone for repair.² Proteins help form collagen, the matrix of bone, and also assist the body in absorbing calcium, another crucial nutrient for bone health. This protein matrix is continuously remodeled, requiring a steady supply of amino acids and minerals to support bone formation and maintenance throughout life.³

Growth factors (GFs) are regulatory proteins stored in the extracellular matrix (ECM) that also play a significant role in bone repair. Released by the ECM, cells, and platelets after injury, these factors are expressed during various healing phases. They act as chemical messengers, stimulating cell growth, differentiation, survival, inflammation, tissue repair, chemotaxis, and ECM formation.⁴

The Process

Inflammation Phase: After a fracture, an inflammatory response is triggered, which leads to the recruitment of immune cells and the release of cytokines and growth factors. These elements initiate the healing process by attracting mesenchymal stem cells to the injury site.

Repair Phase: Growth factors like Bone Morphogenetic Proteins (BMPs), Transforming Growth Factor-beta (TGF-β), and Platelet-Derived Growth Factors (PDGF) stimulate the differentiation of MSCs into chondrocytes (cartilage-forming cells) and osteoblasts (bone-forming cells). This results in the formation of a soft callus made of collagen and cartilage, which eventually mineralizes into a hard callus of new bone.

Remodeling Phase: Proteins like osteocalcin, osteonectin, and osteopontin are involved in remodeling the newly formed bone. Osteoclasts resorb the temporary bone, while osteoblasts create new, stronger bone tissue, restoring the bone to its original shape and strength.⁵

Successful bone regeneration requires the delivery of sufficient growth factors to the injury site at the right time, with adequate responding cells available. In cases of extreme defects or in patients with multiple risk factors where bone repair is impaired, clinical research indicates that supplementing a bone graft with additional proteins and growth factors can aid the healing process and promote new bone formation.⁶

Types of Bone Grafts That Include Proteins and Growth Factors

Bone grafts that incorporate proteins and growth factors are designed to enhance healing by stimulating cellular activity, often using components that promote bone growth and regeneration.

• Demineralized Bone Matrix (DBM): DBMs are created from allograft bone that has been processed to remove minerals, leaving behind proteins and growth factors, particularly BMPs, to stimulate bone formation.
  
  
• Cellular Grafts: Some grafts are enriched with mesenchymal stem cells, which produce growth factors and have the potential to differentiate into bone-forming cells. These grafts are often paired with scaffolds to support structure and healing.
  
  
• Allograft-Derived Proteins: Proteins, growth factors, and peptides are excised and collected during tissue processing to create a convenient, standalone mixture that can be applied to supplement any commercially available scaffold.
  
  
• Synthetic Bone Grafts with BMPs: Certain synthetic grafts are infused with recombinant BMPs, such as BMP-2 or BMP-7, which have shown to significantly enhance bone formation and regeneration.
  
  
• Platelet-derived growth Factor (PDGF)-Infused Grafts: These grafts are designed to enhance healing by stimulating cell growth and division. They are sometimes used with synthetic graft materials or allografts to promote rapid bone regeneration.
  
  
• Autografts with Platelet-Rich Plasma (PRP): When autografts are combined with PRP, they benefit from concentrated growth factors such as PDGF and TGF-β, which can accelerate healing.
  
  
• Grafts with Bone Marrow Aspirate (BMA): BMA contains stem cells and growth factors, which, when combined with a scaffold or graft material, enhance bone growth. This combination supports natural healing processes with osteogenic and osteoinductive properties.

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103284/
2. https://journals.lww.com/nutritiontodayonline/fulltext/2019/05000/optimizing_dietary_protein_for_lifelong_bone.5.aspx#:~:text=Protein%20makes%20up%20roughly%2050,one%2Dthird%20of%20its%20mass.&text=The%20bone%20protein%20matrix%20undergoes,bone%20across%20the%20life%20span.
3. https://www.centerfororthosurgery.com/nutrition-and-bone-health-supporting-recovery/#:~:text=They%20play%20a%20vital%20role,diet%20may%20help%20alleviate%20this
4. https://pubmed.ncbi.nlm.nih.gov/19043663/
5. https://pubmed.ncbi.nlm.nih.gov/22293759/#:~:text=The%20course%20of%20bone%20healing,on%20the%20role%20of%20inflammation.
6. https://www.mdpi.com/2306-5354/10/11/1252#:~:text=To%20achieve%20successful%20bone%20regeneration,sufficient%20vascular%20supply%20%5B2%5D.