A Pertinent Primer On Current Orthobiologics

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If The Panelists Had To Choose One Orthobiologic ...

Editor’s note: With the June cover story, “A Guide To Orthobiologics In Podiatric Surgery,” leading surgeons discussed indications and their use of orthobiologics in a roundtable format. Unfortunately, due to space constrictions, one of the questions posed by Mark Dollard, DPM, wound up on the cutting room floor. In this online exclusive, here is the remaining question from the roundtable and the panelist responses.

Mark Dollard, DPM: You are performing a talonavicular arthrodesis on a desert island. You have limited instrumentation and only one screw. Which orthobiologic material would you chose and why?

A: D. Scot Malay, DPM, says a single screw, usually a 6.5 mm interfragmental compression screw, should be sufficient. He uses it routinely when fusing the talonavicular joint as an isolated procedure or as a component of triple arthrodesis. If the fusion interface is flush and well coapted, and there are no cystic changes or cancellous voids, he does not see an indication for the use of a bioceramic conductor material in the isolated fusion. When performing a triple arthrodesis, Dr. Malay does pack the sinus tarsi with a combination of calcium phosphate and DBM. For an isolated fusion in a healthy adult, he adds DBM paste to the arthrodesis interface. If a patient has any other risk factors (such as tobacco use, neuropathy or a previous nonunion) for delayed union or nonunion, he adds a bone marrow aspirate and DBM to the construct.

“I think that judicial use of any and all of these agents is less expensive than dealing with a nonunion,” says Dr. Malay. “Moreover, use of orthobiological materials decreases the need to harvest as much, or any, autogenous bone graft, thereby reducing operating time, blood loss, complications and costs related to the additional procedure.”

Dr. Malay says the synthetic and demineralized materials are very safe, aside from a low risk of an immunological or infectious complication related to allogenicity. Although harvesting autogenous marrow cells carries some surgical risks, he notes the risks are small and complications are not likely if the procedures are performed properly. As he says, the risk of complications is far smaller than the risk associated with harvesting a corticocancellous bone graft.

If Glenn Weinraub, DPM, had to choose one material, he would use Platelet Gel Concentrate. He says the material is cost effective and provides a large amount of growth factors to create an inductive cascade.

Opteform (Exatech) is the choice for Thomas Zgonis, DPM. The allograft, he notes, has corticocancellous bone chips for osteoconduction and demineralized bone matrix (DBM) for induction. He says such one’s choice would need to accept the compression from the single screw and become solid at body temperature. In addition, Dr. Zgonis says such a product should not wash out after irrigation, must be firmed at the surgeon’s needs and provide mechanical integrity at the arthrodesis site.

Kieran Mahan, DPM, would use a large fragment solid screw with the Healos bone substitute/autogenous marrow combination. As an alternative, he chooses autogenous cancellous bone.

In contrast, Luis Leal, DPM, would not choose a product, saying such a procedure, when performed in a concentric fashion with minimal cartilage resection, should produce little to no bony deficit. If there is bony deficit or Dr. Leal wants to add a stress relief graft, the navicular tuberosity is readily available. However, if he had to choose one product, he would use the Therics graft (Therics), which he says one can easily shape and pack around the joint space that requires fusion. He says the Therics graft has a defined shape and internal architecture that provides for controlled graft resorption, which he notes is critical in fusion procedures where remodeling is important for a stable bony mass.

Here is a view of AlloMatrix-C, a demineralized bone matrix hybrid composite.
Here one can see a triple arthrodesis (performed in 1986) with residual rearfoot valgus and forefoot supinatus.
In this one-year, post-op view, note the incorporation of the Silver and Cotton osteotomies with the freeze-dried allograft bone.
Here is a 20-year follow-up photo of the Silver and Cotton osteotomies with the freeze-dried allograft bone.
Note the double osteotomy correction of the residual rearfoot valgus and forefoot supinatus. The surgeons performed Silver and Cotton osteotomies, and utilized implanted freeze-dried allograft bone. (Photos courtesy of Mark Dollard, DPM, FACFAS)
Here are three-month (top) and seven-month (bottom) post-op views of an Evans calcaneal osteotomy with freeze-dried allograft. Note the rapid incorporation of the Evans osteotomy and allograft with creeping substitution.
Here is an 18-year follow-up radiograph that shows full incorporation of the freeze-dried allograft and the Evans calcaneal osteotomy.
A Pertinent Primer On Current Orthobiologics
A Pertinent Primer On Current Orthobiologics
A Pertinent Primer On Current Orthobiologics
A Pertinent Primer On Current Orthobiologics
A Pertinent Primer On Current Orthobiologics
A Pertinent Primer On Current Orthobiologics
A Pertinent Primer On Current Orthobiologics
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Author(s): 
By Mark D. Dollard, DPM, FACFAS, and Glenn Weinraub, DPM, FACFAS

   Surgeons have traditionally relied upon autografts, replacement bone from sources within the patient’s own body, as the gold standard for graft remodeling in bone fracture and primary osseous repair. While autograft bone is superior in its ability to provide osteogenic mesenchymal stem cells (MSCs), it has the inherent problem of limited supply and morbidity associated with harvesting from donor sites. Given these limitations, there has been a need for orthobiologic bone substitutes and these products continue to emerge and evolve as viable graft alternatives.

   Before we take a closer look at osteogenic substitutes, osteoinductive substitutes and osteoconductive substitutes, it is important to have a strong understanding of the major classifications of bone graft donor resources. The four major physiologic classifications of bone grafts substitutes are autogenous, allogenic, xenografts, inorganic or synthetic.

   Autogenous bone is derived from the individual patient. Although it provides vital mesenchymal stem cells, growth factors and natural bone matrix platforms, the harvest potential of autogenous bone is limited in its supply source from the iliac, fibula, rib and calcaneal bone sites. Although the favorable histocompatibility of the autogenous graft is unquestioned, its osteogenic content may vary depending on the physiologic age of the patient and the population of stem cells derived from the bone marrow source.

   Young individuals typically have an approximate ratio of one mesenchymal stem cell to 10,000 other bone marrow cells/unit area. In the aged individual, that ratio may be decreased to one stem cell to 1 million to 2 million bone marrow cells. Accordingly, the harvest potential of pluripotent stem cells from an individual may be inconsistent to meet our grafting goals. Current research efforts are focused on isolating and procuring a higher yield of individual MSCs from either bone marrow or adipose tissue sources. Through bioengineering techniques, researchers may be able to differentiate these stem cells into osteoprogenitor cells and add them to conglomerate implantable materials.

   Allogenic bone is typically derived from the same cadaveric species and is either “frozen” or “freeze-dried.” Although allogenic bone materials are made readily available, their osteogenic potential may be hampered during the processing of these materials. Sterilization by gamma irradiation may harm an allograft’s molecular growth factors, reducing both their chemotactic and MSC derivative potential. However, sterilization by the ethylene oxide process maintains the viability of protein growth factors such as bone morphologic protein (BMPs).

   Xenografts (i.e. graft from alternative animal species) are only referenced here in passing. Various problems have been encountered from histocompatability reactions with host tissue stemming from both the xenograph’s cellular components that do not wash out during processing and from their molecular matrix structures. Inflammatory reactions from synthetic polymers are still of concern. However, crystalline matrixes derived from coral hydroxyapatite and inorganic calcium hydroxyapatite have value. We will discuss these later for their utility as scaffolds.

Understanding Key Structural Differences

   The substantive difference between hard cortical versus soft cancellous bone that varies the utility for these materials is gross mechanical strength. While cortical bone offers good strong structural support, it incorporates slowly via creeping substitution into the bony defect. Cancellous bone offers a great deal of osteogenic cellular components, matrix structure and growth factors for both the stimulation of bone repair and the conduction of graft incorporation.

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