Autogenous and Allogenic Stem Cell Usage in Foot and Ankle Fusions Bradly W. Bussewitz, DPM and Christopher F. Hyer, DPM, FACFAS Abstract: Orthobiologics are helping surgeons to manipulate healing and reduce delayed unions and nonunions. Surgeons are no longer limited to harvesting the iliac crest to obtain osteoconductive, osteo- inductive, and osteogenic materials for grafting purposes. Synthetic substitutes have evolved that have nearly unlimited volume, no associated harvest site morbidity, and may even eclipse the healing capabilities of autogenous grafts. Mesenchymal stem cells, available both by bone marrow aspirate harvest and by commercially available allografts, provide adjuncts to facilitate bone healing in foot and ankle surgery. Key Words: bone marrow aspirate, mesenchymal stem cells, orthobiologic, biologics, nonunion (Tech Foot & Ankle 2011;10: 28--32) HISTORICAL PERSPECTIVE The pathways for fracture healing and bone fusion are known, but the intimate details continue to be researched and understood. Many factors are needed to achieve bone fusion, including, but not limited to surgical technique and fixation, patient physiology and comorbidities, the effects of drugs and toxins (ie, smoking), and in the case of foot and ankle, weightbearing forces. However, the patient’s innate healing response or capacity cannot be underestimated. Many studies have shown the negative healing effects of poorly controlled diabetes, malnutrition, vitamin D and calcium deficiencies, and an increased risk of postoperative infection, to name a few. 1–6 We are beginning to learn some of the chemical and cellular factors active in the complex bone-healing cascade. In general terms, it is well understood that there are 3 entities involved in bone healing: (1) osteoconduction: a substrate or scaffold for bone growth, (2) osteoinduction: protein signals and regulators that ‘‘induce’’ bone formation. These chemical signals act as attractive and activation signals to upregulate bone production and downregulate bone breakdown. In addition, they signal the recruitment of progenitor cells and signal them to differentiate to bone-producing osteoblasts, and (3) osteogenic: the actual progenitor cell, which can differ- entiate into bone producers. These mesenchymal stem cells (MSCs) are the cells that physically lay down the new bone. As we look into the 3 crucial properties to augment bone fusion, we have many options with which to manipulate the healing environment. Scaffolds or bone void fillers, such as allograft cancellous bone, synthetic calcium, and phosphate substrates, in addition to collagen and ceramic grafts are all options. For inductive properties, platelet-derived growth factors such as the transforming growth factor-b superfamily can be supplied by the platelet-rich plasma concentration systems or even recombinant bone morphogenic proteins can be dosed off the shelf. For the third property, actual living progenitor cells, as of now 2 options exist: (1) autologous grafts in the form of autogenous bone graft or bone marrow aspirate (BMA) or (2) allograft by commercially available allograft stem cell bone grafts. MSCs have many abilities, including differentiating into osteoprogenitor cells. MSCs originate in many tissues, includ- ing fat and bone marrow, and in other tissues as well, and primarily reside there and also in the circulating blood. 7 The traditional gold standard for bone grafting relied on autologous sources, as all 3 traits were found. In addition, recipient rejec- tion is not an issue, as there is perfect compatibility, and both corticocancellous and purely cancellous grafts can be obtained. Unfortunately, limited volume is available. For foot and ankle surgeons, common harvest locations include the iliac crest, tibia, and calcaneus. Harvest site morbidity and pain is also a concern, particularly from the crest. Exogenous-sourced grafts may be able to attain equiv- alency with autografts when combining osteogenic cells and inductive proteins into the mix. An exogenous source may be actually preferable for many reasons: (1) harvest site morbidity, (2) inadequate volumes/quantity, and (3) cost limitations by increased procedure codes and operating time and the treatment of complications related to the harvest site. Autograft harvest morbidity include fracture, hemorrhage, pain, nerve or arterial injury, and cosmetic disturbance. 8–11 Bone grafting is common in foot and ankle surgery, as bone void replacements/fillers and as graft in lengthening procedures. Implanting strictly osteoconductive grafts, such as frozen allografts, requires the recipient site to provide healing or incorporation of the graft. Success using these grafts is documented for use in the calcaneus, specifically the Evans lateral column lengthening procedure. 12 The calcaneus is notorious for its bountiful blood supply and healing ability. However, nonunions do occur and augmentation with osteoinductive or osteogenic agents may facilitate healing. In less-vascular locations of the foot and ankle, even in an otherwise healthy individual, delayed unions or nonunions can be relatively common. Nonunions can have disastrous results and should not be disregarded. Surgical procedures on naive tissue allows the surgeon an optimal chance at healing. Bone stock has not been violated iatrogenically, tissue planes are more easily deci- phered, and blood supply has not been disrupted. The cost of a nonunion can be substantial when considering testing, time away from work, and revision surgery, if necessary. It is the authors’ opinion that methods to increase the chance of boney consolidation should be used to avoid the pitfalls of delayed or nonunions. Frequently, this includes the use of allogenic bone combined with autogenous BMA and MSC concentrate. INDICATIONS AND CONTRAINDICATIONS Proactive but judicious use of orthobiologics may be used in an effort to gain solid bone arthrodesis and reduce the chance of Copyright r 2011 by Lippincott Williams & Wilkins From the Orthopedic Foot and Ankle Center, Westerville, OH. Address correspondence and reprint requests to Bradly W. Bussewitz, DPM, Orthopedic Foot and Ankle Center, 300 Polaris Parkway Suite 2000, Westerville, OH 43082. E-mail: ofacresearch@orthofootankle.com. SPECIAL FOCUS 28 | www.techfootankle.com Techniques in Foot & Ankle Surgery  Volume 10, Number 1, March 2011