Bone defects of the jaws: moving from reconstruction to regeneration

Bone grafting

Embryologically, bone may be classified as intramembranous or endochondral. Intramembranous ossification occurs in the so-called membrane bones of the skull, eg frontal, parietal, temporal, occipital, maxilla, mandible and flat bones, whereas endochondral ossification is characteristic of the bones of the trunk and extremities.18 The principle of replacing like with like should generally be adhered to and therefore bone of intramembranous origin should be used to reconstruct mandibular defects. It has been reported that membranous bone grafts maintain better volume because of their larger cortical and smaller cancellous components, along with a faster revascularization process.19 Bone grafts can be of three different types:

Autogenous bone grafts refer to bone harvested within the same individual. This is the gold standard for reconstruction as it contains viable and immunocompatible osteoblastic cells that are needed to regenerate bone.^2,17Figure 3 illustrates an autogenous ramus graft augmenting a bony defect in the maxilla.

Three types of autogenous bone graft can be harvested:

Cancellous bone grafts contain higher quantities of viable osteoblasts than either cortical or corticocancellous grafts and therefore a higher percentage of viable cells survive during the transplantation procedure.^2,17

One of the difficulties associated with autogenous bone grafts is obtaining sufficient quantities of bone for grafting, while minimizing risks during harvesting, such as donor site morbidity, inflammation and resorption of the implanted bone.^2,17 Therefore, autogenous grafting is only indicated when restoring small mandibular defects.

Allografts refer to grafts harvested from another individual of the same species. The most commonly used allograft for mandible reconstruction is freeze-dried bone. In 1965, Marshall reported on the benefits of using allogenic bone grafts for osseous repairs.18 Such bone grafts are suitable for small defects where the continuity of the mandible is intact. The main drawbacks with allografts are vulnerability to infection, antigenicity and concerns with regards to potential disease transmission.17

Xenografts refer to material harvested from a different species17 and they can be used to restore small bony defects. They show a high degree of osseoconductivity and have a slow resorption profile which contributes to the stability of newly generated bone. Bio-Oss^®, a bovine-derived deproteinized bone, is one such material. It has been utilized successfully for over 20 years with clinical uses in bone augmentation, sinus elevation, repair of furcation lesions and intrabony defects.20

Alloplastic materials

Several alloplastic materials are available to restore osseous defects (Table 1) with variable success rates. Such biomaterials can be broadly categorized into calcium phosphate-based ceramics and cements, synthetic polymers and, most recently, tissue-engineered bone substitutes. Hydroxyapatite (HA) is a calcium phosphate material; a major component in bone and teeth. It is available in naturally-occurring or synthetic forms. Synthetic calcium phosphate (CaP) ceramics, such as beta-tricalcium phosphate (β-TCP), are engineered to resemble that of cancellous bone and therefore used to restore cancellous defects. HA cements have been used since the early 1990s as multipurpose bone substitutes for filling calvarial defects and contouring facial skeleton abnormalities. However, they lack sufficient tensile and compressive strength and therefore cannot be used in load-bearing applications.21

Bioactive glass is a synthetic, osteoconductive, silica-containing particulate bone filler that is used for restoring surgical or traumatic bone defects. It can be used in combination with autogenous bone particles and demineralized bone matrix, leading to accelerated bone healing compared with bone grafting alone.21

Medpor is a biocompatible, porous, high-density polyethylene implant material, which has been used successfully for aesthetic contour enhancement and reconstruction of the facial skeleton. It is long-lasting, with a low frequency of complications. Associated morbidity is similar to procedures involving autologous grafts, and overall patient satisfaction is high.21

Organic calcium salts and synthetic materials such as methylmethacrylate, proplast and teflon have been used with limited success. In general, alloplastic materials' lack of osteo-inductive properties and absence of vascularity and cellular components contra-indicates their use in radiated or poorly vascularized tissue.17

Vascularized free flaps

Over the past 20 years the use of vascularized bone grafts has become common practice for mandibular reconstruction, with success rates of over 90% reported. The most usual donor sites for osseous tissue transfer include the fibula, scapula, iliac crest and radius.16

Fibula free flaps (FFF) (Figure 4) are most commonly used for mandibular reconstruction. This is an excellent choice for reconstructions that require primarily bone and in cases where the native mandible is atrophic.3 It allows for significant bone transfer (max 25 cm in length) and is thus ideal for reconstruction of large defects.^2,3,17 The FFF is based on the peroneal artery and its accompanying veins. The fibula graft allows placement of osseointegrated implants to support dental prostheses and can be contoured, thereby improving aesthetics and function.22

Scapular osteocutaneous free flaps are indicated where there is a full thickness defect, such as those involving facial skin, bone and mucosa.22 It is based on the circumflex scapular artery and its accompanying veins. The vascular pedicle, which is 6–9 cm, is of sufficient length to reach recipient vessels in the neck.^3,17,23 Osseointegrated implants can be placed in most cases to aid with dental prostheses.22

Development of the iliac crest free flap has significantly improved the surgical restoration of the mandible. This donor site provides a long vascular pedicle, appropriately shaped bone, and is advantageous for lateral and hemimandibulectomy defects.17

Radial forearm free flaps can be successfully used to restore small mandibular defects but are not ideal for reconstruction of large defects. This is due to unacceptable donor site morbidity when harvesting a large amount of bone, including a limited range of motion, grip strength and supination.22 The length of the radius bone that can be harvested safely without unacceptable forearm dysfunction is limited to 10–12 cm with recommendations to harvest only up to 40% thickness of the circumference of the radius, to minimize the risk of subsequent pathological fractures.17 It can easily bear tissue-borne prosthesis and, in fact, provides a better contour for support of tissue-borne prosthesis than either the fibula or scapular composite free flaps.22

Guided bone regeneration (GBR)

Guided bone regeneration encourages bone growth in the site of a defect. GBR protects the defect against population by epithelial and connective tissue to allow the space to be inhabited by bone cells that grow into the area of the defect. The available preclinical and clinical evidence suggests that GBR continues to be a successful adjunct in peri-implant bone defects and preservation of alveolar bone following extraction of teeth.14

Over the past number of years, non-immunogenic and resorbable biomaterials are becoming the basis for complete and predictable guided bone regeneration in many cases. GBR, using expanded polytetrafluoroethylene (e-PTFE) membranes has become an accepted method for promoting bone growth adjacent to oral implants.27Bio-Gide^®, a porcine resorbable bilayer collagen membrane is currently used in periodontal, peri-implant applications or to improve the ossification of bone defects of any origin. It consists of a smooth and a rough surface. The smooth surface is covered by a particularly dense film, designed to prevent the invasion of soft tissue in a membrane-protected bone defect and the rough side is designed to promote bone ingrowth.28

Distraction osteogenesis (DO)

The discovery of DO was made by a Russian orthopaedic surgeon, Professor Gavriil Ilizarov in 1954 when, by chance, he observed callus formation in a patient who mistakenly distracted his frame instead of compressing it.29

Distraction osteogenesis is a technique to lengthen bones without the use of grafting material (Figure 5). This technique can be particularly useful for congenital deformities of the mandible.30 It is the process of new bone generation through the gradual separation of segments of existing bone.2 An average growth of 10 mm in bone height is reported with DO when used to reconstruct the mandible.22 The advantages and disadvantages of DO are outlined in Table 3.

Bone morphogenetic proteins (BMPs)

BMPs are multi-functional growth factors belonging to the transforming growth factor beta (TGFβ) superfamily.31 Extraction, purification and cloning of the protein morphogens has led to therapeutic strategies for regeneration of human bone.^2,22 Recombinant human bone morphogenic protein-2 (rhBMP-2) and -7 (rhBMP-7) are used for spine and long bone non-union, as an alternative to autologous bone grafts. In the head and neck region, this concept is applied in alveolar regeneration and in sinus floor procedures. Regeneration of 6 cm segmental bony defects in the mandible have recently been reported.32

Stem cells

Stem cells are unique cells found in multi-cellular organisms and they have the following specific features:

There are two different types of stem cell:

Embryonic stem cells (ESCs) are derived from embryos. They can differentiate into over 200 different cell types found in the body and renew almost any tissue and are therefore classified as pluripotent stem cells. Adult stem cells (ASCs), also known as somatic stem cells, are usually found in a specific tissue or organ in the body and they have limited differentiation capacity. Their main function is to maintain and repair tissue in which they are found and therefore are regarded as multipotent cells.13 ASCs can be harvested from many organs and tissues as demonstrated in Table 4.

Contentious issues surrounding the use of ESCs, including development and subsequent destruction of embryos, forced scientists to seek other methods of culturing stem cells. This led to the innovation of induced pluripotent stem cells, whereby ASCs are reprogrammed to behave like ESCs and have the potential to develop into any cell type. This new technique could exclude the possible problems associated with immune rejection, ethical obstacles and issues with tumorigenicity.13 Dental pulp stem cells (Figure 6) represent an adult stem cell population that is readily accessible from extracted teeth.33 There are recent reports on the successful induction of pluripotency in cells of dental pulp origin.