Skeletal reconstruction

Introduction

Skeletal reconstruction in the lower limb can be challenging for both orthopedic and plastic surgeons. Bony defects may be encountered in isolation, for instance after oncologic resection, while more commonly complex cases with coexisting soft-tissue defects can result after trauma or chronic infections. Moreover, traumatic injuries already treated with internal fixation can become complicated resulting in non-unions, which requires surgical debridement and subsequent reconstruction of the bony defect.

Several approaches have been used by orthopedic and plastic surgeons, with favorable results. Conventional reconstructive techniques include corticocancellous bone graft, autologous non-vascularized fibular grafts, vascularized bone grafts, allograft, and distraction osteogenesis. However, successful reconstruction demands a comprehensive evaluation of the patient and the existing defect, a meticulous surgical procedure, as well as an accurate knowledge of the biological mechanisms of bone tissue healing. The purpose of this chapter is to outline the best reconstructive options for bone defect of the lower limb according to the anatomic site.

Biology of bone healing and grafting

Bone has an incredible restorative ability, compared to the repair mechanisms of the other tissues and organs, that allows an effective regeneration with return to its pre-injured state. Proper healing of bone tissue is influenced by several factors. Accurate knowledge of these factors are required so that regenerative process takes place without any complications. The importance of adequate immobilization has been known for thousands of years, and we are beginning to understand the biologic components critical to successful bone healing, i.e., the importance of progenitor cells, presence of a favorable scaffold, as well as adequate perfusion. The absence of any of these components invariably impedes bone healing.

After an injury, a cascade of healing events consisting of three biological stages begins, including an acute inflammatory response followed by a repair mechanism and the final step of remodeling. During the first, inflammatory phase, a hematoma forms around the blood vessels of the injured tissue. At this stage, cellular components associated with inflammatory response like neutrophils contribute fibrin thrombus by depositing a fibronectin matrix, and macrophages are induced. These inflammatory associated cells also remove the necrotic cells and debris, and release cytokines and growth factors (GFs) at the site of the tissue injury. The released GFs and cytokines then signal migration and differentiation of mesenchymal stem cells (MSCs) from bone marrow and periosteum. The next steps are cellular differentiation toward osteoblasts, formation of a repair blastoma , and subsequently deposition of new osteoid at the injury site followed by bony callus formation. The remodeling , or final healing phase, consists of reorganization and reshaping of collagen fibers and creation of bone tissue with a strong lamellar structure. The final process slowly progresses and ultimately the bone exhibits characteristics of a strong pre-fracture structure.

In the beginning of the healing process, inflammation plays a critical role. The release of proinflammatory cytokines (interleukins, such as IL-1 and IL-6, or TNF [tumor necrosis factor]) induces chemotactic effects that attract inflammatory cells. Molecular signaling mechanisms are activated to stimulate the formation of blood capillaries ( angiogenesis ) at the injury site. Molecules such as GFs associated with bone regeneration include BMPs (bone morphogenetic proteins), FGF (fibroblast growth factor), IGF (insulin-like growth factor), vascular endothelial GF (VEGF) and TGF-β (transforming growth factor β) are recruited. Among BMPs, the most important signaling ligands are BMP-2, BMP-4 and BMP-7 and therefore these have become a focus of scientific attention. The US Food and Drug Administration (FDA) has approved these ligands to be incorporated in bone regeneration protocols and devices.

Understanding these biological principles is important as they have direct therapeutic consequences. According to the FDA, a fracture that has not healed after nine months, and does not show any signs of healing for three consecutive months, is considered a non-union. The prevalence of non-union fractures ranges from 5% to 10%, depending on the anatomic region, severity of the injury to the bone, surrounding soft tissue, vascular structures, and the definition used for a non-union. Indeed, a non-union may be classified as hypertrophic, oligotrophic, or atrophic. While the presence of hypertrophic non-union is indicative of excessive motion due to inadequate fixation, the diagnosis of atrophic non-union poses greater therapeutic challenges. The former clinical scenario reflects adequate healing capacity and is best treated by rigid fixation, while the latter requires additional measures to augment local bone healing, such as bone grafting.

A thorough understanding of the mechanisms by which bone grafts and bone substitutes facilitate bone healing is mandatory to allow the reconstructive surgeon to make the correct choices when attempting reconstruction. Bone grafts heal through several mechanisms that include osteoconduction, osteoinduction, and osteogenesis.

Osteoconduction represents the ingrowth of MSCs, capillaries, and perivascular tissues from the recipient site into the transplanted graft, i.e., scaffold. Osteoinduction is the recruitment of MSCs with subsequent differentiation to chondroblasts and osteoblasts, and is modulated by growth factors, e.g., BMPs. Osteogenesis is synthesis of new bone by viable cells within the graft.

Autologous bone grafting is considered the gold standard because it allows osteoconductive, osteoinductive, and osteogenic mechanisms which promote bone healing. However, the type of graft chosen for reconstruction presents a different distribution of these properties. Autologous bone grafts can be classified as non-vascularized bone grafts (i.e., conventional cancellous and cortical bone grafts) and vascularized bone grafts (or vascularized bone flaps).

Cancellous bone grafting is certainly the most common bone grafting technique: it is characterized by a remarkable osteogenic potential, which is due to the large number of osteocytes and osteoblasts that remain viable due to the rapid revascularization that occurs if the graft is placed in a well-vascularized wound bed. Its drawback, however, is its limited structural integrity. On the other hand, cortical bone grafts are strong constructs. Nevertheless, the revascularization process is slower because of the cortical density. Indeed, these grafts incorporate by a process known as “creeping substitution”, which represents gradual resorption of the graft with subsequent deposition of new bone (i.e., osteoconduction).

Bony flaps are bone segments harvested that include a vascular pedicle. Thus, after successful transfer and revascularization at the recipient site, cells within the graft survive and heal to the surrounding bone by primary and secondary bone healing, rather than by “creeping substitution”. Their advantages include viability and subsequent quick healing and capability of growth and hypertrophy in response to stress, load bearing (Wolff law), vascularity, resistance to infection, and additional environmental signals.

The perfusion pattern of any given bone determines the technique of flap harvest. The blood supply to long bones derives from multiple sources. The nutrient artery supplies the bone marrow and inner cortex, while the periosteal vessels supply the outer diaphyseal cortex. Additional metaphyseal and epiphyseal vessels traverse the cortex and have an anastomotic arcade with the nutrient artery. For instance, a long-bone free flap, such as the fibula, can remain viable with its periosteal blood supply only.

The dual blood supply of long bones is contrasted by the predominantly periosteal blood supply of membranous bones. An example is the iliac crest free flap, first described by Taylor, which is based on a periosteal pedicle derived from the deep circumflex iliac artery (DCIA).

In contrast to autologous bone, the reconstructive surgeon has the option to use allografts for the purpose of skeletal reconstruction. Drawbacks of autologous bone, such as limited autogenous supply of bone and donor site morbidity, are thus averted. Allografts are functionally strong, but their incorporation remains questionable, since they own merely osteoconductive properties: as they do not contain viable cells, they are not osteogenic. However, they may gain osteoinductive properties when combined with growth factors, e.g., BMPs. Moreover, they have been associated with relatively high complication rates that include non-union, fracture, and infection, all of which necessitate their removal. Recently described techniques combine the initial structural integrity of the allograft with a vascularized bone flap, to take advantage of both methods.

In summary, the decision regarding the bone grafting technique depends on a variety of different factors, including the anatomic location and 3D configuration of the defect, soft-tissue envelope, limb vascularity, overall patient condition, as well as availability of donor bone. The ideal reconstruction is characterized by quick bone healing and minimal donor site morbidity, ultimately resulting in functional restoration of the extremity.

Historical perspective

Reconstruction of the lower limb can be complex. To understand contemporary problems and target areas for improvement, the history of lower limb reconstruction must be examined. The first bone graft was a dog-to-human xenograft performed in 1668 by Job Janszoon van Meekeren. In 1861, Ollier demonstrated experimentally that bone fragments could survive as a graft, although the first human autograft had been performed prior to this by von Walter (1820). William Macewen performed the first human allograft of bone in 1880. However, bone transfers remained unpopular right through the modern era. Religion was not entirely to blame. A lack of understanding of transplant biology produced spectacular failures, including one belonging to a surgeon named Phelps. He transferred a pedicled bone flap from a dog into the tibial defect of a boy. Animal and child remained connected by the pedicle for 2 weeks. The failed flap was removed 5 weeks later.

Autologous bone grafting finally achieved popularity after F. H. Albee published a book on the subject in 1915. With increased use came recognition of its limitations, including long-segment defects of the lower limb. The void was filled when the evolution of bony reconstruction and microsurgery crossed paths in 1975, based on the work of Taylor. The use of free flaps was an improvement on conventional bone grafting but involved functional downgrade of the donor limb by virtue of transient leg weakness, ankle instability, and great toe contracture. This problem was obviated with the introduction of distraction osteogenesis.

The distraction procedure was first described by Alessandro Codivilla in 1905 but was plagued by treatment failures. By accident in 1943, Ilizarov had overcome these. His device was originally designed to treat hypertrophic non-union with compression osteosynthesis. One day, the nuts on the device were turned the wrong way such that the fracture was distracted. New bone was seen on radiograph between the distracted bone ends. The device was patented in 1951 but was prevented from reaching the West by the Iron Curtain until the early 1980s. Italian explorer Carlo Mauri had suffered a chronic, infected tibial non-union refractory from the treatment he received in his home country. Ilizarov cured him of the ailment on his travels to the East. Distraction osteogenesis was a revolution because it provided stable fixation and autogenous bone without donor site morbidity.

Methods of skeletal reconstruction

Several variables must be considered to personalize, as much as possible, any single reconstruction. Etiology, dimension, location, contamination rate, and associated soft-tissue injury must be carefully evaluated. Oncologic defects are surgical, thus by definition sterile; on the other hand, post-traumatic defects, particularly if complicated by severe soft-tissue injury, are contaminated. In these cases, aggressive debridement of infected and nonviable tissues with immediate but temporary bone stabilization should be performed. In any case, the bony reconstruction should be attempted when the infectious risk is dramatically reduced. In selected cases, a two-stage reconstruction, including a first step to position a cement spacer and flap coverage, may be indicated.

What is not always straightforward is how to create a stable skeletal reconstruction. A thorough understanding of the methods of skeletal reconstruction and the limitations of each approach is mandatory to maximize the potential for skeletal stability.

A wide range of treatment modalities is available. These include conventional, such as cancellous or corticocancellous bone grafts, bone pedicled or free flaps (with or without associated soft-tissue component), non-vascularized allografts and distraction osteogenesis. These techniques are not mutually exclusive and may be combined to extend the capability of one approach alone. Reconstruction of large bony defects is limited by available autologous donor sites. Although allogeneic bone grafts have been used, another alternative being investigated experimentally is the use of culture-expanded autologous osteocytes which are grown in the recipient on polymer scaffolds.