Biologics in Spine Surgery: From DBM to Stem Cells

Achieving a solid arthrodesis (fusion) is the primary goal of most spinal reconstructive surgeries. Without fusion, instrumentation eventually fails. Historically, the Iliac Crest Bone Graft (ICBG) was the "Gold Standard," but high rates of donor site morbidity (pain, infection, fracture) have driven the industry to develop alternatives.

Today, the biologics market is a billion-dollar industry filled with marketing hype. It is the surgeon's responsibility to understand the basic science behind these products to choose the right graft for the right patient.

The Physiology of Fusion

To obtain a fusion, you need three elements: Stability, a Decorticated Bed, and the Biologic Material.

Visual Element: Diagram of the "Bone Healing Triad" (Cells, Signals, Scaffold).

The properties of a bone graft are defined by the "Three O's":

1. Osteoconduction (The Scaffold):
   • The physical matrix that provides a trellis for new bone to grow into.
   • Examples: Ceramics (TCP/HA), Collagen sponges, Allograft bone chips.
2. Osteoinduction (The Signal):
   • Growth factors that recruit mesenchymal stem cells (MSCs) and stimulate them to differentiate into osteoblasts.
   • Examples: BMP-2, Demineralized Bone Matrix (DBM).
3. Osteogenesis (The Cells):
   • Living cells (Osteoblasts/Osteocytes) that survive transplantation and produce new bone.
   • Examples: Autograft, Bone Marrow Aspirate (BMA), Cellular Allografts (Stem cells).

1. Autograft: Still the King?

• ICBG: Contains all three properties (Conductive, Inductive, Genic).
• Local Bone: Bone harvested from the laminectomy/facetectomy. It is primarily cortical (conductive) with less cellularity than iliac crest.
• Current Status: Local bone is used in almost every case. ICBG is now reserved for challenging non-unions due to pain.

2. Allograft: The Workhorse

Bone from a cadaver.

• Structural Allograft: (e.g., Femoral ring). Provides structural support (Conductive) but has no living cells. Used for anterior column support.
• Morselized Allograft: Freeze-dried chips. Purely conductive scaffold.

3. Demineralized Bone Matrix (DBM)

• Process: Cadaveric cortical bone is acid-washed to remove the mineral phase. This exposes the native BMPs trapped in the collagen matrix.
• Properties: Osteoconductive + Osteoinductive (Weak).
• Variability: The concentration of BMP varies wildly between donors and processing methods. Some batches have high potency; others are inert.
• Clinical Use: An "extender." Mix it with local bone to increase volume. Do not rely on it as a standalone graft in a smoker.

4. Synthetics (Ceramics)

• Materials: Tri-Calcium Phosphate (TCP), Hydroxyapatite (HA), Bioglass.
• Properties: Osteoconductive ONLY.
• Mechanism: They mimic the mineral composition of bone. They are porous. Over time, they dissolve (creep substitution) and are replaced by host bone.
• Clinical Use: Must be mixed with BMA (for cells/signals) or local bone. Cheap and safe (no disease transmission risk).

5. Bone Morphogenetic Proteins (rhBMP-2)

• Brand: INFUSE (Medtronic).
• Properties: Super-Osteoinductive.
• Mechanism: Recombinant DNA technology produces massive amounts of BMP-2. It forces undifferentiated cells to become bone.
• The YODA Project: Early industry trials underreported complications. Independent review (YODA) revealed risks:
  • Radiculitis: Inflammation of nerve roots.
  • Ectopic Bone: Bone growing where it shouldn't (e.g., into the canal).
  • Cervical Swelling: Contraindicated in anterior cervical spine due to airway compromise.
  • Cancer Risk: Theoretical, debated, but generally disproven in long-term follow-up.
• Clinical Use: The "Nuclear Option." Use for high-risk patients (Smokers, Diabetics, Revisions, ALIFs).

6. Cellular Bone Matrices ("Stem Cells")

• Concept: Cadaver bone processed to remove immunogenic markers while preserving live MSCs.
• Properties: Theoretical Osteogenesis.
• Controversy: Critics argue that few cells survive the processing, freezing, and thawing. They are often termed "Expensive Dead Bone."
• Cost: Extremely expensive ($2k-$5k per level).
• Verdict: Evidence is mixed. Most surgeons prefer BMP or Autograft for the same price.

Decision Making Algorithm

How do you choose? Base it on the Host Grade and the Fusion Environment.

Visual Element: Flowchart "Biologic Selection Algorithm".

Low Risk Scenario

• Patient: Non-smoker, healthy, single-level ACDF or PLIF.
• Graft: Local Bone + Synthetic/DBM Extender.
• Reasoning: The fusion bed has high surface area and stability. Expensive biologics are a waste of money.

Moderate Risk Scenario

• Patient: Smoker, 2-3 level fusion, TLIF.
• Graft: Local Bone + BMA + High-quality DBM.
• Reasoning: Need more induction. BMA adds cells.

High Risk Scenario

• Patient: Revision surgery, Osteoporosis, Long-construct deformity (T10-Pelvis), Pseudoarthrosis repair.
• Graft: BMP-2 (Off-label in posterior spine) or ICBG.
• Reasoning: You need the "Big Gun." The environment is hostile (scar tissue, poor vascularity). Failure leads to rod fracture.

Future Directions

• Peptide-Enhanced Ceramics: Synthetics coated with a specific protein sequence (e.g., P-15) to recruit cells without the side effects of BMP.
• 3D Printed Scaffolds: Titanium cages with porosity and modulus matched to bone, reducing the need for graft inside the cage.

Conclusion

Biology matters. No amount of titanium can overcome a failure of biology. While local bone remains the foundation, the judicious use of DBM, Synthetics, and BMP allows surgeons to tackle increasingly complex cases. Be skeptical of marketing claims; ask for Level 1 evidence.

Clinical Pearl: When using BMP, keep it away from the dura to prevent radiculitis. Place it anteriorly in the interbody space or laterally in the gutters, covered by a sponge or local bone.

References

1. Carragee, E. J., et al. (2011). "A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery." The Spine Journal.
2. Fischer, C. R., et al. (2013). "Systematic review of bone graft substitutes for posterior lumbar fusion." Global Spine Journal.
3. Dimar, J. R., et al. (2009). "Clinical and radiographic analysis of an optimized rhBMP-2 formulation as an autograft replacement in posterolateral lumbar spine arthrodesis." JBJS.