A Pertinent Primer On Current Orthobiologics

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.

   Although cancellous grafts incorporate faster, their porous nature tends to lack structural integrity against strain deformation. Accordingly, surgeons often need to utilize either internal/external fixation or immobilization to augment structural support during early phases of cancellous bone incorporation.

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