h1 class=”calibre8″>22 Bone Graft Options, Substitutes, and Harvest Techniques

Arash J. Sayari, Ankur S. Narain, Fady Y. Hijji, Krishna T. Kudaravalli, Kelly H. Yom, and Kern Singh

Keywords: cervical spine, bone graft, demineralized bone matrix, bone fusion, iliac crest bone graft, allograft, bone graft substitute

22.1 Introduction

Anterior and posterior cervical fusion techniques are commonly utilized in the treatment of traumatic cervical pathologies. The achievement of adequate bony fusion during these procedures is of paramount importance. Adequate fusion not only ensures spinal stability, but is also associated with improvements in postoperative outcomes related to pain, disability, and neurological deficits. ^1,2,3,4 Failure of bony fusion or pseudarthrosis following cervical procedures is of significant concern. Symptomatic pseudarthrosis can lead to recurrence of pain and is responsible for a large percentage of revision procedures for cervical pathology. ^5,6,7,8

In order to aid in the fusion, a variety of bone grafts and graft alternatives can be utilized. Bone grafting in humans was first documented as an allograft procedure in the late 1800s when William MacEwen replaced the proximal two-thirds of a humerus in a 4-year-old boy with bone transplanted from his other patients. ⁹ In the lumbar spine, Albee described the placement of cortical tibial autograft into a split spinous process during the treatment of Pott disease. ¹⁰ In cervical spine applications, Smith and Robinson described the technique of anterior cervical discectomy and fusion (ACDF) with a novel method of placing a horseshoe-shaped tricortical graft from the iliac crest. ¹¹ Similarly, Cloward reported a method of obtaining bone graft from the anterosuperior ilium for use in anterior cervical fusion procedures. ¹²

Within current practice, autografted bone transplanted from one anatomic site to another remains the gold standard in bone grafting for cervical fusion procedures. However, advances in graft technology have produced viable alternatives to autograft such as allograft, graft enhancers, and graft substitutes. With the plethora of fusion materials available, it is imperative that surgeons understand the relative efficacy of each potential option. As such, the purpose of this chapter is to review the varying types of fusion biologics with a focus on their appropriate use in the setting of cervical trauma (▶ Table 22.1).

22.2 Biology of Bone Grafts and Fusion

The three most commonly cited elements of graft osteointegration are related to its osteoconductive, osteoinductive, and osteogenic potential. Proper understanding of this relationship between the host and graft is crucial as this forms the basis of graft design and choice. Osteoconductive properties relate to the three-dimensional graft–host environment, allowing for further ingrowth of tissue, capillaries, and multipotent stem cells (MSCs). The scaffold by which these MSCs function makes way for the creation of Haversian canals and bone growth.

Osteoinductive properties relate to the graft’s availability of growth factors and its ability to stimulate bone growth. ¹⁵ Osteoinductive grafts recruit MSCs, which differentiate into chondroblasts and osteoblasts that form novel bone via endosteal ossification. ¹³ Molecular studies have shown that autograft contains various growth factors that regulate the recruitment and differentiation of the MSCs. The growth factors implicated in bone growth, development, and repair include the transforming growth factor beta (TGF-β), superfamily of proteins (TGF-β1 and bone morphogenetic proteins [BMP] types 2, 4, and 7), fibroblast growth factor alpha (FGF-α), insulin-like growth factor 1 (IGF-I), granulocyte colony-stimulating factors, platelet-derived growth factor-bb (PDGF-bb), and endothelial-derived growth factors. ¹⁶ Many of these growth factors also serve as inflammatory cytokines, hence explaining why anti-inflammatory agents are not recommended during the early stages of bone healing and repair. ¹⁴

Finally, the osteogenic potential of a graft is related to its concentration of MSCs and osteoprogenitor cells that can differentiate into osteoblasts and eventually, osteocytes. Only fresh autologous grafts, and autologous and allografted bone marrow transplants possess these properties and contain viable cells capable of directly producing bone.

22.3 Autograft

Autograft is bone graft obtained from a patient’s own bone that is transplanted at the recipient site. In cervical procedures for both traumatic and nontraumatic etiologies, autograft is the gold standard graft choice due to its superior osteointegrative potential and lack of immunogenicity. Autograft can be characterized based upon its location with distinctions made between local autograft from the operative site and autograft taken from other anatomic locations. The most commonly utilized location for autograft harvest is the iliac crest. Iliac crest bone grafts (ICBG) have demonstrated successful fusion outcomes in both lumbar and cervical spine applications. In addition, autograft can be classified based on the type of bone graft obtained, such as cancellous, cortical, vascularized, or bone marrow aspirate.

22.3.1 Cancellous Bone Autograft

Cancellous bone, the most commonly used form of autograft, provides a scaffold through which further bone growth can occur. Like cortical bone, graft transplantation involves gradual graft resorption, bony remodeling, and novel bone formation via creeping substitution. ^17,18 After transplantation, bleeding and inflammation serve as the foundation for this process. Recruitment of MSCs allows for fibrous granulation in the graft bed in as little as little as 2 days. ¹³ In addition, macrophages utilize chemotaxis to gather at the site of transplantation in order to begin degradation of necrotic tissue. Revascularization is completed rapidly in an end-to-end or appositional fashion. MSCs from the host and graft cells begin to differentiate into osteoprogenitor cells and eventually osteoblasts that line the graft–host interface to deposit osteoid. However, there is still the presence of necrotic tissue centrally. Inward osteoclastic resorption of this tissue is followed by increased osteoblastic activity to replace the once vacant lacunae with new bone. The final step is continuous remodeling, which can take up to a year to complete. ¹⁸

The trabecular environment of cancellous bone has a high surface area, thriving with MSCs, osteoblasts, and osteocytes, thus leading to superior osteoconductive, osteoinductive, and osteogenic properties. ^14,16,19 This concept is quite apparent in decortication during cervical fusion procedures. When the intramedullary spaces of the posterior elements of the spine are exposed (lamina, pedicles, transverse processes), pluripotent stem cells within the marrow infiltrate the fusion site to provide osteogenic proteins and a rich blood supply to the graft–host interface.

These advantages also support why cancellous graft does not offer the same mechanical strength as cortical graft. In fact, cancellous bone is only one-fourth as dense as cortical bone and should, therefore, be more commonly used for filling small defects rather than being used as supportive strut. However, because of its relatively rapid incorporation, cancellous autograft initially strengthens over the necrotic center. The increased early stability is produced as bone is initially laid down but normalizes over time. Locally available autograft should be used if possible, especially in single-level procedures. It is easily incorporated into the surgical site and has demonstrated fusion rates in the lumbar spine similar to that of ICBG. ^20,21

22.3.2 Cortical Bone Autograft

Autologous cortical bone graft behaves differently, most notably with a rate of revascularization nearly half that of cancellous bone due to its density and highly organized Haversian and Volkmann canals. In both cancellous and cortical autografts, creeping substitution follows in a centripetal pattern to allow for new bone formation. However, osteointegration of cortical autograft is initially dictated by osteoclasts, rather than osteoblasts. The rate of osteoclastic resorption rises from 2 weeks through 6 months post transplantation, after which the rate declines to near-normal levels at 1 year. ¹⁴ Along the process of inward resorption, osteoblasts begin laying down bone to eventually replace the transplanted cortical autograft with new, viable bone. As osteoclastic activity dictates cortical autograft remodeling, initial bone loss may result in the graft losing a significant amount of its strength due to removal of its necrotic center, but eventually will fully heal with near-normal mechanical strength. This was demonstrated in a mechanical study performed by Enneking et al on 23 canines in which fibular autografts were examined. The transplants demonstrated increased porosity and weakness at 6 weeks, but 100% of them had achieved normal mechanical strength by 12 months. ²² Given that only 60% of their study subjects had full remodeling of the transplants, this further exemplifies how the mixture of necrotic and viable bone does not influence the overall strength.

As there are fewer osteocytes, osteoblasts, and infiltrating MSCs in cortical bone graft, it consequently exhibits poorer osteogenic, osteoinductive, and osteoconductive potential than cancellous grafts. However, cortical autograft offers increased initial mechanical strength and increased stability when used as a bony fixation construct.

22.3.3 Autologous Vascularized Bone Graft

Vascularized grafts are those transplanted with their arterial and venous vessels anastomosed during grafting, allowing for more rapid graft incorporation. An adequate anastomosis allows for more than 90% survival of osteocytes and other osteoprogenitor cells. ²³ In addition, vascular cortical grafts heal quickly because the revascularization component is essentially complete, allowing for a remodeling process similar to that of normal bone by way of primary or secondary bone healing. Thus, there is no sacrifice of early mechanical strength due to creeping substitution as exhibited with nonvascularized autografts. The primary concern with vascularized grafts is difficulty in obtaining and correctly transplanting these grafts. These grafts involve challenging techniques of orthopaedic and microvascular surgery with increased operative times and blood loss during harvest.

The most commonly used vascularized graft is the free fibula strut graft transplanted along with its peroneal artery. Prior to graft harvest, preoperative angiography may be useful to evaluate vascular pedicles. ²⁴ In the case of short peroneal artery pedicles, iliac crest grafts with branches of the deep circumflex iliac artery and distal radius grafts with the intercompartmental supraretinacular artery may be suitable alternatives.

As vascular grafts are most useful in massive spine defects caused by tumors and deformities, their use is not common in the setting of cervical spine trauma. Regardless, consideration for fibular strut grafts continues to be made, as its strength in the axial plane is nearly five times that of ICBG. ²⁵

22.3.4 Autologous Bone Marrow Aspirate

Although bone marrow aspirate (BMA) is not technically a bone graft and is less commonly used than cortical or cancellous grafts in cervical fusions, it deserves mention because of its osteogenic properties and other key advantages. Using minimally invasive techniques, BMA can be easily obtained from the iliac crest or vertebral body. The biological properties of BMA that make it useful as an autograft stem from the presumed concentration of MSCs that reproduce and differentiate into connective tissue. Specific to bone, this differentiation produces osteoblasts via medullary osteogenesis.

While BMA offers theoretical advantages, the true number of stem cells that can differentiate into osteoblasts are variable in BMA and may be as few as 1 in 50,000 in the young patients and 1 in 1,000,000 in the elderly. ¹⁴ Recent investigation regarding the influence of BMA on bone remodeling and repair has been focused on its concentration of endothelial progenitor cells and ability to stimulate revascularization. ²⁶ This relates to the osteoinductive properties of BMA as it contains chemotactic mitogens that induce and attract local growth factors.

Unfortunately, given its semiliquid state and lack of structural support, BMA tends to migrate from initial transplantation site. Thus, BMA may be less favorable in anatomic sites, such as the cervical spine, as BMA fluid migration has been linked to heterotopic ossification. ¹⁵ Despite efforts being made to mix BMA with cancellous bone and bone graft substitutes to mitigate some of these disadvantages, ^27,28 the clinical use of BMA in the cervical spine has been minimal thus far. As recent attempts have been made to incorporate BMA into substrates and extenders, such as demineralized bone matrix, potential still exists for BMA to gain traction in the future.

22.3.5 Autologous Platelet-Rich Plasma

Platelet-rich plasma (PRP) is prepared from an autologous supply of whole blood which then undergoes specific centrifugation protocols to provide a high concentration of platelets. This suspension is filled with growth factors such as TGF-β, PDGF, and vascular endothelial growth factor (VEGF). The conglomerate platelet solution is mixed with calcium chloride to create a platelet clot applied at the surgical site. Recent investigation has found a link between PRP, callus formation, and cell proliferation. ²⁶ Feiz-Erfan et al randomized 50 patients with degenerative disc disease or disc herniation to receive either cervical allograft or cervical allograft plus platelet concentrate. ²⁹

Related posts:

Traumatic Atlantoaxial Rotatory Fixation Cranioskeletal Traction for the Management of Trauma to the Cervical Spine Traumatic Cervical Myelopathy Penetrating Injuries to the Cervical Spine Clinical Trials Update: Where Do We Go from Here? Initial Assessment (Including Imaging) of Cervical Spinal Cord Injury

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