FormalPara Introduction and Core Messages

Bone grafts or substitutes are used in spinal surgery to fill defects, to bridge defects or to promote spondylodesis. The physiological process is similar to that of fracture healing and incorporates the same spatial and temporal factors. The ideal material should provide osteogenetic, osteoinductive and osteoconductive properties. The traditional autologous bone grafts are probably still considered the “golden standard”, but the problems associated with them bring up the need for substitutes. One alternative is the acquirance of allogenic or xenogenic bone grafts, which have specific problems of their own, which limit their use. The other aspect is the use of bone substitutes, which come in a growing variety of materials, shapes and application forms. Currently, none of these substitutes unite all of the prerequisites shown above, but they have the advantage of unlimited supply without causing additional problems such as donor site morbidity. And the combination of such substitutes as scaffold with the utilization of growth factors and mesenchymal stem cells brings with them a completely new array of possibilities.

1 Definition

1.1 Bone Graft

The bone is harvested from different parts of the patient. It is most commonly from the iliac crest but also from the vertebral structures, the ribs, the tibia as well as the fibula [1].

1.2 Bone Graft Substitute

It replaces the autologous bone in order to achieve defect filling and bridging and also fusion [2]. It provides unlimited supply and eliminates donor site morbidity. But no substitute provides the combination of osteoinductive, osteoconductive and osteogenetic properties [1].

2 Physiology of Bone Regeneration

The bone is one of the few organs that retains the potential for regeneration throughout life. In contrast to other organs, the bone does not repair defects with scar material of poor quality but rather reinstates its original values. But fracture healing and therefore also bone regeneration are complex physiological processes.

Two basic principles of bone healing are described in literature [3] as follows:

  • Primary bone healing (“direct healing”) is very rare and not the usual form of healing achieved in spinal surgery.

  • Secondary bone healing involves intramembranous and endochondral ossification and leads to callus formation. Callus formation is achieved through undifferentiated multipotent mesenchymal stem cells (MSCs) and requires cell vitality and blood supply.

In this cascade of bone regeneration, certain prerequisites are known. Most importantly, a vital cell population has to be present. MSCs have to be either present or transferred to the site via blood supply. These cells are transferred to a cell population with osteoblastic phenotypes.

In addition, the fracture haematoma offers a vast supply of signalling molecules (ILs, TNFs, TGFs, VEGF) to induce healing. Within the group of TGFs, the so-called bone morphogenetic proteins (BMP-2, BMP-7) have been extensively studied and shown to play a decisive role in the healing process [4]. The third important element is the extracellular matrix, providing a natural scaffold for the cellular interactions. This can be replaced by an immense number of osteoconductive materials such as allografts, demineralized bone matrix (DBM), hydroxyapatite and calcium-based ceramics, among others. These scaffolds have been shown to have an optimal pore size of 150–500 μm. The last important factor, important for fracture healing and bone formation, is the mechanical stability. All four components combined are described as the “diamond concept” (Fig. 12.1). It is well described in extremity fractures and of equal importance in spinal surgery [5].

Fig. 12.1
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“Diamond concept” regarding bone healing [5]

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3 Clinical Application

Therefore, bone or bone substitutes should preferably have the three properties mentioned above. Osteogenicity refers to the fact that they contain osteoblastic cells and are thereby capable of directly forming the bone. Osteoconductivity refers to the situation in which they provide a structure along which osteoblasts can attach and thereby the bone can grow. Osteoinductivity is the ability to induce nondifferentiated stem cells or osteoprogenitor cells to differentiate into osteoblasts. A “perfect” bone graft substitute would incorporate all three characteristics.

4 Autologous Bone Grafts

The “golden standard” of bone grafts is the autologous bone, although it is an area of growing controversy [1]. It is mostly harvested from the iliac crest, depending upon positioning of the patient. This donor site has the advantage of having a supply of the cancellous as well as cortical bone (tricortical graft) (Figs. 12.2 and 12.3).

Fig. 12.2
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CT scans in three planes documenting the correct size and positioning of a tricortical autograft

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Fig. 12.3
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Plain radiograph of a monosegmental, anterior spondylodesis with a tricortical iliac crest autograft following bisegmental, posterior stabilization

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Advantages

  • Osteogenetic

  • Osteoconductive

  • Osteoinductive

Disadvantages

  • Limited supply.

  • High failure rate is reported.

  • Risk of iliac crest fracture (Fig. 12.4).

  • Correctional loss due to remodelling [6].

  • Donor site morbidity (limited with correct utilization).

  • Additional operation time.

Fig. 12.4
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Iliac crest fracture following bone harvest from the anterior iliac crest in the right side

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Harvest sites

  • Iliac crest (anterior, posterior)

  • Locally (vertebral body, spinous process, lamina, etc.)

  • Rib portion (in transthoracic approaches)

  • Tibia/fibula

5 Surgical Technique of Iliac Crest Graft Harvesting

The bone from the iliac crest can be easily harvested. When choosing the anterior crest, one must be aware of the lateral femoral cutaneous nerve. On the other hand, a safety margin of at least 3 cm should be left from the anterior superior crest, where the hip flexion muscles derive from. We recommend harvesting the graft using a double-blade oscillating saw. The desired depth can also be harvested using a “graft cutter”. This way a defined cortical graft is obtained, leaving room for additional harvesting of cancellous bone chips using a spoon. The defect is filled using a haemostatic pad, the fascia is closed and a drain should be placed to prevent a painful haematoma. Alternatively, according to the clinical application, “bone plugs” can also be harvested using special instruments (Fig. 12.5). This leaves less defect and can also be harvested in other locations.

Fig. 12.5
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Bone graft harvesting set (Synthes) used for different sizes of “plugs” (© by Synthes)

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6 Bone Graft Substitutes

These materials should ideally have the osteogenetic, osteoconductive and osteoinductive characteristics of an autograft without the substantial side effects. Most of these materials only provide osteoconductivity. Their integration into the bone substance can take place in different ways [7]. One way is the direct integration or resorption followed by conversion into the bone. The other way would be some kind of “graft-versus-host reaction” resulting in a self-contained graft or even a (partial) loss of graft substance without integration [8].

7 Allografts

This relates to the tissue taken from one person for transplantation into another. This type of treatment has spread due to recent improvements in procurement, preparation and storage. Clinics with a high turnover of allografts have their own storage areas. This concept of bone banking is connected to a great deal of legal issues, showing great variations in different countries [9]. They are useful however to enlarge the volume of the autologous bone.

Advantages

  • Osteoconductive

  • Unlimited supply

  • Multiple shapes and sizes

  • No donor site morbidity

Disadvantages

  • Not osteogenic (due to chemical processes in the making)

  • Weak osteoinductive properties

  • Possibility of infectious disease transmission

8 Demineralized Bone Matrix (DBM) and Bone Morphogenetic Protein (BMP)

DBM is a demineralized allograft bone with osteoinductive activity [10]. Demineralized bone matrixes are prepared by acid extraction of the allograft bone, resulting in loss of most of the mineralized components but retention of collagen and noncollagenous proteins, including growth factors. The efficacy of a demineralized bone matrix (DBM) as a bone graft substitute or extender may be related to the total amount of bone morphogenetic protein (BMP) present and the ratios of the different BMPs present. The multitude of different BMPs are all capable of recruiting bone-forming cells and encouraging local cells to aid in the bone formation process. There are up to now over 20 different BMPs known, but the clinical research is currently limited to BMP-2 and BMP-7. The different types of BMPs seem to show substantial variations in their osteogenetic potency. Recently, BMP has been associated with cancer, but further studies have found no correlation [11].

Advantages

  • Osteoinductive with promoted bone formation [12].

  • Osteoinductive potency is very variable in different products [4].

  • Graft extender (in combination with autografts).

Disadvantages

  • Poor structural integrity

  • BMP alone not osteoconductive

9 Hydroxyapatite (Ca10(PO4)6(OH)2) and Tricalcium Phosphate (Ca3(PO4)2)

These substitutes are mainly known as bone void fillers. Taking into account their specific strengths (e.g. fast curing, fluid injection, etc.) and their weaknesses (low shear stress, poor biodegradability, etc.), new applications have arisen. These materials come in a wide array of different application forms (Fig. 12.6).

Fig. 12.6
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An array of different forms and shapes used in calcium phosphate bone substitutes (© by Synthes)

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Advantages

  • Osteoconductive (Fig. 12.7)

  • Lasting stability

  • Availability

Fig. 12.7
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(a, b) Histological findings using chronOS mixed with blood 6 weeks (a) and 12 weeks postoperatively (© by Synthes)

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Disadvantages

  • Not osteoinductive

  • Not osteogenic

10 Clinical Application

Current evolutions within this field, such as biphasic, injectable CaP and silicated CaP, widen the array of applications, offering a good supplement in achieving spinal fusion [13] (filling cages, lining cages, extending grafts, etc.) (Table 12.1). These substances should be rehydrated using the patients’ blood before applying (Fig. 12.8).

Table 12.1 Exemplary list of calcium phosphate products on the market (among others)
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Fig. 12.8
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ChronOS blocs mixed with blood (© by Synthes)

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11 Other Ceramics (Sea Corals, Calcium Sulphate)

These substances are currently researched to evaluate their usefulness to supplement or even replace the ceramics in use today.

12 Outlook

Tissue engineering and the further development of growth factors offer great potential for the future of fusion and bone substitutes. Materials will evolve and offer “ideal” and individual solutions for specific indications [14]. But currently, the autologous bone is still the golden standard [15]. The diversity of current substitutes will make further comparative studies quite difficult.