Keys To Optimal Selection Of Orthobiologics

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

Given the adjunctive potential of orthobiologics in facilitating bone healing, these authors offer a closer look at osteoconductive agents such as calcium sulfate and osteoinductive agents such as PRP and demineralized bone matrix, and the emerging literature on these modalities.

The musculoskeletal system has the extraordinary ability to regenerate itself. This property is shared with only a couple of systems (the liver and the hematopoietic system) in the human body. Bones are able to reconstitute into the same shape and size, and are able to withstand the same load as pre-injured bone. The ability to harness this mechanism has implications for reconstructive foot and ankle surgery.

   The reality is that bone healing following elective surgery or trauma does not always go as expected. Complications such as delayed union, malunion and nonunion can occur. There are many factors that can contribute to a nonunion including: the presence of systemic diseases such as diabetes mellitus; pharmaceuticals that can adversely affect bone healing; infection; inadequate fixation; poor vascularity; bone and soft tissue defects; smoking; and nutritional deficiencies.

   There has been an explosion in new technologies available to enhance bone healing in foot and ankle surgery. Not only have superior fixation constructs been engineered but there has also been an increase in the number and types of orthobiologics in the marketplace. Today, a myriad of commercially available bone grafts, bone graft extenders and osteobiologics have been developed for day-to-day use. Accordingly, let us review the basic science and take a closer look at the clinical application of orthobiologics as they apply to foot and ankle surgery.

An Overview Of The Mechanisms Of Orthobiologic Substrates

Osteoconduction is the process by which a biologic scaffold provides the framework for passive ingrowth of mesenchymal stem cells (MSCs), angiogenesis and the migration of bioactive signaling molecules.

   Osteoinduction is the mechanism by which mesenchymal stem cells are recruited to the surgical site and activated to differentiate into chondroblasts and osteoblasts. This pathway leads to new bone formation through endosteal ossification. This complex pathway is mediated by soluble growth factors including bone morphogenetic proteins (BMPs), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF).

   Osteogenesis comprises the pathway in which mesenchymal stem cells, osteoblasts and osteocytes are transplanted locally or from another site for the purpose of osteosynthesis. This is achieved by utilizing autogenous graft from the host or through a bone marrow transplant.

   Osteopromotion involves the utilization of agents to enhance bone healing that is already taking place.

Pertinent Insights On Osteoconductive Agents

Osteoconductive orthobiologics are scaffolds that have similar structural integrity of cancellous bone but lack the combination of osteoinduction and osteogeneic properties of true cancellous autograft. Osteoconductive agents serve as scaffolds on which osteoblasts can lay bone or as a mineral repository for cartilaginous calcification following their own resorption. These scaffolds passively allow ingrowth of host capillaries, perivascular tissue and mesenchymal stem cells, thereby fulfilling a permissive role in allowing new bone growth.1 These bone substitutes are available in powders, putty, pellets and as implant coatings for joint prostheses.

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