Keys To Optimal Selection Of Orthobiologics

Author(s): 
Phillip E. Richardson, DPM, Brian T. Dix, DPM, Adebola T. Adeleke, DPM, John M. Baca, DPM, Robert Mendicino, DPM, FACFAS, and Alan R. Catanzariti, DPM, FACFAS

   Surgeons can use osteoconductive orthobiologics as void fillers, infection eradicators (in combination with antibiotics) and graft expanders when they combine them with autogenous grafts or bone morphogenetic proteins. Researchers are currently looking at the efficacy of adding collagen, growth factors and mesenchymal stem cells to augment the biological activity of these products, and there is a growing need for further studies of these products in the lower extremity.

A Primer On Platelet-Rich Plasma

Platelet-rich plasma (PRP) is a volume of fractionated plasma of the patient’s blood that has platelet concentrations above normal levels in the body (150,000/μL-350,000/μL).7,8 In the last decade, platelets have gained intense popularity as an adjunctive treatment for musculoskeletal injuries.9

   Specifically, platelets originate within the bone marrow from megakaryocytes. Circulating in the blood, they are non-nucleated, colorless, discoid-shaped cells that carry granules (α, δ, λ).10,11 Platelets are activated and aggregate together shortly after tissue damage with the alpha (α) granules releasing many proteins. Within 10 minutes of aggregation, platelets begin secreting these proteins and more than 95 percent are released within one hour.7,11 The most relevant ones secreted for healing are insulin-like growth factor (ILGF), epidermal growth factor (EGF), transforming growth factor (TGF-β1), PDGF, FGF and VEGF among many others.10,12-14

   This complex signaling cascade ultimately leads to recruitment of mesenchymal stem cells and fibroblasts, collagen formation, angiogenesis and smooth muscle formation.14-16 The ideal amount of PRP is unknown but a minimum of 1,000,000/μL is required for tissue healing with no benefit observed over approximately five times normal levels.7,8

   Clinicians obtain PRP by collecting the patient’s blood from a vein and mixing it with an anticoagulant. One then puts the blood into a centrifuge, where it is separated into a top acellular plasma layer (platelet-poor plasma), a middle buffy coat layer (PRP), and a bottom erythrocyte layer (red blood cells). Then the clinician collects the PRP with a syringe or by an automated system. Finally, PRP activates via the addition of calcium chloride or thrombin among other factors.17

   Dohan and coworkers categorized platelet concentrates into four types, relying on fibrin and leukocyte content.17 The first type is pure platelet rich plasma, which is poor in leukocytes. The second is leukocyte rich PRP. The third type is pure platelet rich fibrin, which only encompasses Fibrinet (Vertical Spine).

   The application of PRP for bone healing in the foot and ankle has had some promising results. Two randomized controlled trials (RCTs) found the combination of bone chips with platelet gel and/or bone marrow stromal cells increases the ostegenetic potential of the bone chips, and may be valuable in treating patients with difficulties in bone healing and patients with large bone deficits.18,19 Another RCT looking at the treatment of displaced intra-articular calacneal fractures compared three treatment groups.20 The first group received allograft alone. The second group received allograft and PRP. The third group received autograft plus PRP. The follow-up ranged from 24 to 72 months postoperatively. The researchers went on to find that the groups utilizing PRP had significantly superior outcomes in comparison to the group that received an allograft alone.20

What The Literature Reveals About Demineralized Bone Matrix

Demineralized bone matrix is a family of commercially available products produced from morselized corticocancellous bone, which is extracted from human cadavers.21 This human allograft is washed, deminerialized with organic solvents or acids, dried, prepared and sterilized.5 It is intrinsically osteoinductive and, to a lesser extent, osteoconductive.22 Researchers have shown that the osteoinductivity of demineralized bone matrix is dependent upon the demineralization process and those products washed with hydrochloride (HCl) are superior to those washed with other acids.5,22,23

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