Mikhail L. Samchukov Jason B. Cope Alexander M. Cherkashin Although the application of craniofacial osteodistrac- tion has dramatically increased in the last decade, dis. traction osteogenesis remains one of the most mysteri ‘ous phenomena of bone biology. During distraction, new bone forms under the mechanical condition of ‘gadual incremental traction superimposed on atienu: ated functional loads. Moreover, the nature of this me- chanical environment and the dynamics of the forming regenerate bone are not typical of those found elsewhere inthe skeleton.’ ‘The purpose of this chapter is to summarize the cur- rent knowledge about basic biologic mechanisms in- volved in new bone formation during distraction osteo: genesis. In addition, the dynamics of regenerate bone formation forthe endochondral bones of the axial skele- ton will be compared with that for membranous bones of the craniofacial skeleton BIOLOGIC BASIS OF NEW BONE FORMATION, Distraction osteogenesis begins with the development of a reparative callus between the edges of two bone seg- ments divided by a low-energy osteotomy. After the cal- luis has initially formed, a distraction force is applied to these bone segments and gradually pulls them apart Gradual incremental separation of bone segments places the callus under tension; this aligns the interseg- mentary gap tissues parallel to the direction of distrac- tion. After the desired amount of bone length is achieved, the distraction force is discontinued. The newly formed bone (distraction regenerate) then under. goes maturation and remodeling until it becomes undis- singuishable from the residual host bone. Clinically, distraction osteogenesis consists o quential periods: (1) osteotomy; (2) latency, the dura- tion from bone division to the onset of traction; (3) dis traction, the time when gradual traction is applied and distraction regenerate is formed; (4) consolidation, the period that allows maturation and corticalization of the regenerate afier traction forces are discontinued; and (5) remodeling, which extends from the initial applica tion of full functional loading to the completion of re generate bone remodeling. This same temporal se~ ‘quence will be Tollowed Tor describing the Biologie mechanisms acting during distraction osteogenesis. ‘An osteotomy divides a bone into two segments, result- ing in a loss of continuity and mechanical integrity; this is also referred to as a fracture (Fig. 2-1). Discontinuity ofa skeletal segment triggers an evolutionary process of bone repair known as fracture healing. This process in- volves recruitment of osteoprogenitor cells, followed by cellular modulation or osteoinduction, and establish- ‘ment of an environmental template (osteoconduction), As a result, a reparative callus is formed within and around the ends of the fractured bone segments; under normal conditions, the callus undergoes gradual re- placement by lamellar bone, which is mechanically Traditionally, fracture healing has been described as consisting of six stages or phases: (1) impact, (2) in- duction, (3) inflammation, (4) soft callus, (5) hard cal- lus, and (6) remodeling (Fig. 2-2). The stage of impact takes place at the moment of stress and Tasts until there is complete dissipation of energy, which is absorbed by the bone until failure occurs. The stage of induction pro- vides modulation of cells needed for the repair process. Possible inductors include products of cell death, oxy- gen gradient, electric potential, noncollagenous pro- teins, and others. Liter a ‘The latency period is the period {om bone division to the ofiet wEtmddtion, This period represents the time al- @ nitro” professional eee Seen22 | SECTION BIOLOGIC FOUNDATION Osteotomy Loss of mechanical integrity & continuity Fracture Recruitment of ‘osteoprogenitor cals (0steoinduction) Establishment of an environmental template (osteoconduction) Fig. 2-1 Demonstration of an osteotomy, which divides the bone into two segments and riggers the evolutionary process of fracture healing. | impact. [-— Induction | — Inflammation [-— Soft Callus +— Hard Callus — Remodeling Fig. 2-2 Consecutive stages of fracture healing. lowed for reparative callus formation. The sequence of events occurring during the latency period is similar to that seen during fracture healing, Following the surgical separation of a bone into two segments, a cascade of events takes place.”** Initially, as a result of vascular disruption, a hema- toma forms between and around the bone segments (Fig. 2-3). The hematoma is converted to a clot, and bony necrosis occurs t the ends ofthe fracture segments. ‘There isan ingrowth of vasoformative elements and cap- illaries for the restoration of blood supply, and a tremen- dous amount of cellular proliferation.” This stage of frac- ture healing (stage of inflammation) Jasis from 1103, days, at which time the clotis replaced with granulation tissue consisting of inflammatory cells, fibroblasts, col- lagen, and invading capillaries. °°" Following inlammationis the soft callusstage, which lasts approximately 3 weeks. This period is marked by a Continuous ingrowth of capillaries into the fracture cal- lus. On the fifth day after osteotomy, a minicellular net- work of growing capillary loops is formed in the medullary canal of both proximal and distal segments in the areas adjacent to the fracture line.""” Less differ- entiated, free circulating osteogenic cells are located in- side the terminals of the newly formed capillaries During the soft callus stage. granulation tissue is con- veited to fibrous tissue by fibroblasts.” Cartilage also re- [laces the granulation tissue. This occurs more toward the periphery of the intersegmentary gap than in the cen- tral region (Fig. 2-4) by a front of endochondral ossifica- tion. The amount of cartilage in the intersegmentary gap, is variable. It is more prominent in animals lower on the evolutionary scale and in areas with excessive movements, and low oxygen tension. It seems that if the callus out- {grows its blood supply, cartilage provides a suitable ma- terial that is less demanding of oxygen, which temporar- ily bridges the gap until the blood supply caiches up.* Callus formation is the response of determined os. teoprogenitor cells, originating principally in the petios- teum and endosteum, to a number of activating factors released from freshly injured bone tissue. The mechani. role of callus formation is obvious: it'gradually en- larges the diameter of the segment ends and thereby the ross. sectional area of the segment sites, Histologically, Callus formation occurs tmaily by ature of gap heal ing and“@At%t ¥)positional bone formation, and its “Gy Fifer? proTeseTOnal download the free tal anina at arepdicom orofeeonalive radiograph of a goat g the inflammatory stage A, Osteotomy B, Hematoma. C, tion tissue. Note that due to ingrowth of capillaries and u Bilge Bas of New Bone Formation Under the ftence sf Temion Stes | 23, c a and schematic drawings demonstrating the ranula yendous cellular proliferation, the hematoma between divided bone segments is replaced with granulation tissue, Fig. 2-4 Radiograph of a goat tibia and schematic drawing daring the soft callus stage. A, Latency. B, Soft callus. Note the conversion of the granulation tissue into fibrous and cartilag nous tissues segment ends) serve as a solid base on which new bone tissue is deposited The distraction period is characterized by the applica- tign of traction forces to osteotomized bone segments Bone segments are gradually pulled apart, resulting in formation of new bony tissues within the progressively increasing intersegmentary gap. During normal fracture healing (Fig. 2-5), the fibro- cartilaginous tissue of the soft callus is replaced by os teoblasts into fiber bone (hard callus stage). The carti- lage calcifies as capillaries invade and osteoblasts lay down new bone on the calcified cartilage matrix. The, stage of hard callus lasts 3 to 4 months for many frac Tures and is followed by the stage of remodeling, when fiber bone is slowly remodeled to lamellar bone and the medullary canal is reconstituted. The stage of remodel. ing ends when the bone has completely returned to nor. mal with restoration of the medullary canal ‘During osteodistraction, however, the normal process of fracture healing is interrupted by the application of gradual traction to the soft callus (Fig. 2-6). Through the application of tensional stress to the intersegmentary tis- sues of the soft callus, a dynamic microenvironment is created.'* The tension stress that develops in the gradu- ally stretched tissues stimulates changes at the cellular and subcellular levels. These changes can be character. ized as a growth-stimulating effect and a shape-forming effect The growth-stimulating effect of tension activates the biologic elements of the intersegmentary connective tis sue. This includes (1) prolongation of angiogenesis with increased tissue oxygenation, and (2) increased fibro- blast proliferation with intensification of biosynthetic activiegeatne withpe-forming effect of tension causes an “GA HHRFOP HF OTESSIGAal download the free mal anina at ntrepdicom forofeedonal