**4. Distraction osteogenesis**

"Distraction osteogenesis" (DO) is a biological process involving the formation of new bone between viable bone segments that are gradually separated by incremental traction. Soft tissue envelope (mucosa, muscle, tendon, skin, cartilage, blood vessels and peripheral nerves) beside bone has been also observed to form under tension stress [8, 9]. Experimental studies also have demonstrated formation of the mature lamellar bone by distraction osteogenesis [7, 10, 11].

#### **4.1. History of distraction osteogenesis**

Manipulation of the bone segments was first described by Codivilla in 1905 [12]. Gavriel Awramowitch Ilizarov performed several studies to advance the technique in orthopaedic therapy in 1950s [13–16]. Ilizarov performed this technique in two steps and observed the bone regeneration between the two time periods.

Application of mandibular lengthening in maxillofacial complex with the usage of external fixation device was first performed in a canine animal model by Synder et al. [17] in 1972. In 1977, Michielli and Miotti [18] used internal devices in lengthening of mandible in a canine animal model by gradual distraction.

McCarthy and colleagues [19] first used distraction osteogenesis in human mandible in 1992. Mandibular lengthening in four young patients and bilateral mandibular expansion in one patient were performed by gradual distraction. Since the first mention of distraction osteo‐ genesis in the human mandible, it was recognized that the development of simple, multidir‐ ectional, miniaturized and buried devices would be necessary to broaden the application of distraction osteogenesis throughout the craniofacial skeleton [20].

#### **4.2. Distraction histogenesis and phases**

The gradual increase in soft tissue volume in response to the tension forces applied with bony distraction is called "distraction histogenesis". Conventional LeFort I osteotomy provides immediate bone advancement but, however, does not allow for compensatory growth of the soft tissues. The high rate of relapse after conventional maxillary advancement seems to be a result of scarring and memory of the soft tissues, though the soft tissue often contracts to its pre-operative state. On the other hand, DO creates a gradual increase in the amount of soft tissue by preventing its contraction [21].

In the distraction process, different biologic phenomena are produced and these can be summarized in three phases: **latency phase** is the period between the performance of osteotomy and the start of the traction, during which bone healing begins and soft callus (initial bone formation) is formed. The period is typically between 3–5 days, although in neonates and infants the latency period may be omitted or last only 24 hours. Waiting too long before distraction (beyond 10 to14 days) increases the risk of premature bone union; **distraction phase** is the period in which the process of distraction is activated to transport the bone fragment and the formation of new immature woven and parallel-fibered bone commences. The total time of the distraction phase is customized to the severity of the deformity. This phase usually lasts 1–2 weeks, and the traction modifies the normal development of the regeneration process. In contrast to the latency period, the rate and the rhythm (frequency) of distraction are important factors [22]. If lengthening of the osteotomy site occurs too slowly (<0.5 mm per day), premature bony union prevents lengthening to the desired dimension, whereas if the rate is too rapid (>2 mm per day), a fibrous nonunion will result. Therefore, most reports recommend a distraction rate of 1 mm per day. The ideal rhythm of DO is a continuous steadystate separation of the bone fragments [13–16]. However, this is not practical, and therefore, the recommended distraction frequency is 1 or 2 times daily [23–25]; and **consolidation phase** is the period that allows the maturation and corticalization of the regenerated bone and the surrounding soft tissues adapt to their new positions and lengths. In craniofacial bones, a 3–5 week phase is recommended for children and a 6–12 week phase for adults. In craniofacial skeleton the general rule is that the consolidation period should be at least twice the duration of the distraction phase [22, 26, 27]. The appearance of bone with identical characteristics to those of the initial bone may take more than a year [9].

#### **4.3. Distraction osteogenesis in sagittal maxillary advancement**

**3. Conventional LeFort I osteotomy**

**4. Distraction osteogenesis**

68 Advanced Techniques in Bone Regeneration

**4.1. History of distraction osteogenesis**

regeneration between the two time periods.

animal model by gradual distraction.

**4.2. Distraction histogenesis and phases**

tissue by preventing its contraction [21].

In the treatment of severe hypoplastic cleft palate with conventional LeFort I osteotomy, the major advancement and the extreme discrepancies made stabilization difficult, and the added

"Distraction osteogenesis" (DO) is a biological process involving the formation of new bone between viable bone segments that are gradually separated by incremental traction. Soft tissue envelope (mucosa, muscle, tendon, skin, cartilage, blood vessels and peripheral nerves) beside bone has been also observed to form under tension stress [8, 9]. Experimental studies also have demonstrated formation of the mature lamellar bone by distraction osteogenesis [7, 10, 11].

Manipulation of the bone segments was first described by Codivilla in 1905 [12]. Gavriel Awramowitch Ilizarov performed several studies to advance the technique in orthopaedic therapy in 1950s [13–16]. Ilizarov performed this technique in two steps and observed the bone

Application of mandibular lengthening in maxillofacial complex with the usage of external fixation device was first performed in a canine animal model by Synder et al. [17] in 1972. In 1977, Michielli and Miotti [18] used internal devices in lengthening of mandible in a canine

McCarthy and colleagues [19] first used distraction osteogenesis in human mandible in 1992. Mandibular lengthening in four young patients and bilateral mandibular expansion in one patient were performed by gradual distraction. Since the first mention of distraction osteo‐ genesis in the human mandible, it was recognized that the development of simple, multidir‐ ectional, miniaturized and buried devices would be necessary to broaden the application of

The gradual increase in soft tissue volume in response to the tension forces applied with bony distraction is called "distraction histogenesis". Conventional LeFort I osteotomy provides immediate bone advancement but, however, does not allow for compensatory growth of the soft tissues. The high rate of relapse after conventional maxillary advancement seems to be a result of scarring and memory of the soft tissues, though the soft tissue often contracts to its pre-operative state. On the other hand, DO creates a gradual increase in the amount of soft

In the distraction process, different biologic phenomena are produced and these can be summarized in three phases: **latency phase** is the period between the performance of

distraction osteogenesis throughout the craniofacial skeleton [20].

effect of palatal scarring can result in significant surgical relapse [7].

Maxillary surgical advancement is the most common surgical technique for correcting maxillary hypoplasia in patients with cleft lip and palate. An advancement of more than 10 mm in patients with no cleft and 6 mm in patients with cleft lip and palate is beyond the limit of conventional LeFort I advancement, and in such cases DO for advancement of the maxilla can be used [28–32].

The application of the force according to the center of resistance of the maxilla plays an important role in sagittal maxillary advancement. The mostly desired directions of the maxillary movements in DO are forward and downward. The center of the mass of the maxilla is considered to be located at the apex of the maxillary premolars. When the force is applied at the center of resistance of the maxilla, a straight anterior movement of the maxilla without any rotation is expected. If the same force is applied above, a clockwise rotation will be expected with a predictable increase in over bite and overjet negligible mandibular rotation. If the force is applied below, a counterclockwise rotation will be expected with a tendency of an anterior open bite [33].

External and internal distraction systems can be used for maxillary distraction osteogenesis [34].

#### *4.3.1. Rigid external distraction osteogenesis*

The rigid external distraction (RED) was developed by Polley and Figueroa [26, 35], and is composed by an external bow, which is fixed to the cranium screws, and by a custom-made intraoral splint cemented to the maxillary first molars. External traction hooks with eyelets are soldered to the splint, allowing the connection with the external device via surgical wires [36].

#### *Advantages and disadvantages*

RED devices have the ability to change the distractor vector during the distraction phase. Another advantage of this system is the ease of the installation and removal of the distractors. However, the main disadvantage is that the device is physically and socially inconvenient and uncomfortable for the patients [26, 35, 37, 38].

#### *Technique and protocol*

High-level complete LeFort I osteotomy is the most commonly performed osteotomy since tooth buds are located on a standard level of LeFort I osteotomy line in young patients [1, 36, 39–43]. Standard LeFort I and the 3-piece LeFort I osteotomies are also used with this protocol [7, 26, 35, 44, 45].

After a latency period of 4–7 days, initial activation of the RED device starts. The rate of distraction is 1 mm per day in two or three rhythms. The planned maxillary advancement is usually obtained in 2 to 3 weeks of active distraction. The duration of the activation varies according to the severity of the maxillary hypoplasia; therefore, many authors mention different protocols on this issue. Some activate the distractor until the proper overjet, overbite and stable posterior occlusion are achieved [39], some continued the activation until 5–8 mm of positive overjet is achieved [45], and some activate the distractor until the desired facial profile convexity, skeletal and dental relationships are achieved clinically [1, 7]. Long consol‐ idation period of 8 to 12 weeks is generally accepted in UCLP patients to prevent the risk of possible skeletal relapse [1, 7, 43]. Radiographic bone healing and the presence of cortical outline should be checked using radiographs before removal of the distractors [43]. However, different consolidation period and retention period protocols exist. Nonunion of the external maxillary distraction after a consolidation period of 4–6 weeks was reported by He et al. [41] in 2010. The very first patients of them treated with external distraction had relapse after the early removal of the distractors, so they lengthened the consolidation time up to 12 weeks and had successful results without nonunion. After a consolidation period of 6–8 weeks, distractors and intraoral splints are removed and the maxillary retention by Class III intraoral elastics can be used [45]. Some radical rigid retention periods (consolidation period) such as 2–3 weeks were also mentioned in some studies [26, 39]. In these studies, after the removal of the RED devices, 4–8 weeks of face mask elastic traction at night time were utilized.

#### *Skeletal changes (horizontal and vertical)*

The sagittal maxillary advancement is measured as the forward movement of particular landmarks. Anterior maxillary movement (horizontal change in point A) varies between 8.03 to 13.4 mm [1, 26, 38–45].

For patients undergoing RED devices, the average increase in SNA angle is between 7.6 to 12.4 degrees [26, 38, 40, 42–45].

Clockwise rotation of the maxilla is one of the goals in most of the patients with unilateral cleft lip and palate due to the vertical maxillary growth deficiency. The vertical changes in point A are between −1.3 and −7 mm pointing an inferior movement [26, 43, 44]. Although there can be a positive downward displacement of the maxilla, an undesired counterclockwise rotation of the maxilla can be a result of inconvenient distraction force vector [1, 42]. Desired change in the palatal plane angle varies according to the application point of the distraction force. In patients without secondary alveolar bone graft, distraction force may also lead to a counter‐ clockwise rotation. This reversible undesired rotation of the maxilla can be corrected with the aid of intraoral elastics [1].

#### *Dental changes*

*4.3.1. Rigid external distraction osteogenesis*

70 Advanced Techniques in Bone Regeneration

uncomfortable for the patients [26, 35, 37, 38].

*Advantages and disadvantages*

*Technique and protocol*

[7, 26, 35, 44, 45].

[36].

The rigid external distraction (RED) was developed by Polley and Figueroa [26, 35], and is composed by an external bow, which is fixed to the cranium screws, and by a custom-made intraoral splint cemented to the maxillary first molars. External traction hooks with eyelets are soldered to the splint, allowing the connection with the external device via surgical wires

RED devices have the ability to change the distractor vector during the distraction phase. Another advantage of this system is the ease of the installation and removal of the distractors. However, the main disadvantage is that the device is physically and socially inconvenient and

High-level complete LeFort I osteotomy is the most commonly performed osteotomy since tooth buds are located on a standard level of LeFort I osteotomy line in young patients [1, 36, 39–43]. Standard LeFort I and the 3-piece LeFort I osteotomies are also used with this protocol

After a latency period of 4–7 days, initial activation of the RED device starts. The rate of distraction is 1 mm per day in two or three rhythms. The planned maxillary advancement is usually obtained in 2 to 3 weeks of active distraction. The duration of the activation varies according to the severity of the maxillary hypoplasia; therefore, many authors mention different protocols on this issue. Some activate the distractor until the proper overjet, overbite and stable posterior occlusion are achieved [39], some continued the activation until 5–8 mm of positive overjet is achieved [45], and some activate the distractor until the desired facial profile convexity, skeletal and dental relationships are achieved clinically [1, 7]. Long consol‐ idation period of 8 to 12 weeks is generally accepted in UCLP patients to prevent the risk of possible skeletal relapse [1, 7, 43]. Radiographic bone healing and the presence of cortical outline should be checked using radiographs before removal of the distractors [43]. However, different consolidation period and retention period protocols exist. Nonunion of the external maxillary distraction after a consolidation period of 4–6 weeks was reported by He et al. [41] in 2010. The very first patients of them treated with external distraction had relapse after the early removal of the distractors, so they lengthened the consolidation time up to 12 weeks and had successful results without nonunion. After a consolidation period of 6–8 weeks, distractors and intraoral splints are removed and the maxillary retention by Class III intraoral elastics can be used [45]. Some radical rigid retention periods (consolidation period) such as 2–3 weeks were also mentioned in some studies [26, 39]. In these studies, after the removal of the RED

devices, 4–8 weeks of face mask elastic traction at night time were utilized.

Dentoalveolar sagittal movement can be measured by the dental overjet and the displacement of the upper incisor tip. The increase of the overjet ranged from 12.7 to 15.8 mm, whereas the angular change of the upper incisor according to the palatal plane ranged from −1.2 to 3.6 degrees [7, 26, 42, 44].

#### *Soft tissue changes*

The main changes accompanying RED procedure are located in the upper lip and nasal region, with improved facial aesthetics. In these patients, the profile of the face changes from concave to convex. The increase in facial convexity angle is between 15.59 and 26.2 degrees [7, 26, 39, 43, 44].

#### *4.3.2. Internal distraction osteogenesis*

Internal miniature distractor was first reported by Cohen et al. [20] in 1997 on maxillary distraction in patients with CLP using an internal miniature distractor. This device produced no complications and permitted maxillary and midfacial advancement in patients with CLP and craniofacial syndromes.

Most surgeons accept that advancement of more than 6 mm in patients with CLP and more than 10 mm in non-cleft patients is beyond the present limit of one-stage maxillary advance‐ ment surgery using LeFort I osteotomy, and can only be achieved by distraction osteogenesis [29, 30].

There are many clinical research studies and case reports about sagittal maxillary advancement with DO. The biomechanical effects associated with this procedure still remain speculative. In 2011, we investigated the effects of DO in a patient with CLP using finite element analysis (FEM) and improved this preliminary study with another comparative study in 2014 [4, 46] (**Figures 5**–**8**). Three-dimensional (3D) finite element model (FEM) analysis is a helpful mathematical instrument for use in orthodontics and can determine the amount of stress, strain and displacement in the maxillofacial complex after different loading conditions of force.

**Figure 5.** Three-dimensional finite element model of our patient with unilateral cleft lip and palate. Yellow colours rep‐ resent the boundary conditions at the foramen magnum, upper side of the cranial vault and the zygomatic buttress, where the superior plates of the internal distractor are assumed to be placed.

The results of our study are similar to the clinical outcomes in some ways, and therefore may help surgeons and orthodontists to understand better the therapeutic effect of internal maxillary DO on the basal bones and sutures of the craniofacial system. The displacement distribution in the sagittal plane was asymmetric in the UCLP model rather than the non-cleft model. The non-cleft side of the UCLP FEM showed more anterior displacement than did the cleft side, which can result from the asymmetrical skeletal development of the anatomical structures.

The amount of transversal change at the lateral nasal walls was found to have expanded in both FEMs.

The maxillary rotation showed differences in both models. On the UCLP model, the maxilla rotated in a clockwise direction after maxillary advancement of 6 mm. On the cleft side, more inferior displacements were observed. In the control model, a counterclockwise rotation of the maxilla occurred. This can be the result of different placement of the anterior advancement vector in this finite element model.

Moreover, our results showed that the sagittal distraction forces produced not only advance‐ ment forces at the intermaxillary sutures but also higher stress values at the sutura nasomax‐ illaris, sutura frontonasalis and sutura zygomaticomaxillaris on the cleft side compared to the non-cleft side. In the non-cleft model, relatively high stress values were found at the sutura frontomaxillaris and sutura nasomaxillaris, similar to the findings on the non-cleft side of the UCLP FEM.

**Figure 6.** Displacement distribution in (a) sagittal, (b) transversal and (c) vertical planes after 6 mm of maxillary ad‐ vancement for the UCLP model, respectively.

**Figure 7.** Displacement distribution in (a) sagittal, (b) transversal and (c) vertical planes after 6 mm of maxillary ad‐ vancement for the non-cleft control model, respectively.

**Figure 8.** The magnitude and distribution of the von Mises stresses after 1 mm of maxillary advancement for the UCLP model and for the non-cleft control model, respectively.

#### *Advantages and disadvantages*

2011, we investigated the effects of DO in a patient with CLP using finite element analysis (FEM) and improved this preliminary study with another comparative study in 2014 [4, 46] (**Figures 5**–**8**). Three-dimensional (3D) finite element model (FEM) analysis is a helpful mathematical instrument for use in orthodontics and can determine the amount of stress, strain and displacement in the maxillofacial complex after different loading conditions of force.

**Figure 5.** Three-dimensional finite element model of our patient with unilateral cleft lip and palate. Yellow colours rep‐ resent the boundary conditions at the foramen magnum, upper side of the cranial vault and the zygomatic buttress,

The results of our study are similar to the clinical outcomes in some ways, and therefore may help surgeons and orthodontists to understand better the therapeutic effect of internal maxillary DO on the basal bones and sutures of the craniofacial system. The displacement distribution in the sagittal plane was asymmetric in the UCLP model rather than the non-cleft model. The non-cleft side of the UCLP FEM showed more anterior displacement than did the cleft side, which can result from the asymmetrical skeletal development of the anatomical

The amount of transversal change at the lateral nasal walls was found to have expanded in

The maxillary rotation showed differences in both models. On the UCLP model, the maxilla rotated in a clockwise direction after maxillary advancement of 6 mm. On the cleft side, more inferior displacements were observed. In the control model, a counterclockwise rotation of the maxilla occurred. This can be the result of different placement of the anterior advancement

Moreover, our results showed that the sagittal distraction forces produced not only advance‐ ment forces at the intermaxillary sutures but also higher stress values at the sutura nasomax‐ illaris, sutura frontonasalis and sutura zygomaticomaxillaris on the cleft side compared to the non-cleft side. In the non-cleft model, relatively high stress values were found at the sutura frontomaxillaris and sutura nasomaxillaris, similar to the findings on the non-cleft side of the

where the superior plates of the internal distractor are assumed to be placed.

structures.

both FEMs.

UCLP FEM.

vector in this finite element model.

72 Advanced Techniques in Bone Regeneration

Internal distractors are socially and psychologically more tolerated than the external distrac‐ tors [36, 47–49]. However, there are some disadvantages: (1) the difficulty of the position process, (2) the need for a second operation to remove the distractors, (3) the inability to change the distraction vector during the distraction phase (control of the maxillary segment can be achieved by intraoral elastics by which an adjustment in "molding the regenerate" bone corrects for an error in distraction direction or vector), (4) the difficulty in placement of the two parts of the distractors parallel to each other, (5) the limitation of the distraction length, (6) the discomfort due to the stretch of the buccal tissues by the distractor's rods, (7) the need for pre-operative planning and/or stereolithographic modelling [34, 50–55].

#### *Stereolithographic modelling*

The desired vectors of the maxillary advancement are necessary and can be controlled via stereolithographic models. In patients with CLP, visualization of the bone thickness and decision of the bony cuts and distractor placements should be made on these models preoperatively. However, in some countries there is an extra cost for stereolithographic modelling; therefore, pre-operative planning can also be simulated using specific computer software, which allows for three-dimensional craniofacial reconstruction from computed tomography scan images [51–54, 56] (**Figures 9**–**11**). Three-dimensional finite element model analysis is also a helpful mathematical instrument for use both in orthodontics and in orthopaedics, and can determine the amount of stress, strain and displacement in the maxillofacial complex [4, 57]. However, this technique cannot be used for all patients individually due to the long elapsed time for the analysis.

**Figure 9.** Stereolithographic model of our patient with UCLP.

**Figure 10.** Demonstration of the surgery on the stereolithographic model, bending of the distractor plates during this section, and finally insertion of the bended distractor plates on the model.

**Figure 11.** LeFort I osteotomy, and the checking for the parallelism of the inserted distractor plates using extension rods.

#### *Technique and protocol*

(6) the discomfort due to the stretch of the buccal tissues by the distractor's rods, (7) the need

The desired vectors of the maxillary advancement are necessary and can be controlled via stereolithographic models. In patients with CLP, visualization of the bone thickness and decision of the bony cuts and distractor placements should be made on these models preoperatively. However, in some countries there is an extra cost for stereolithographic modelling; therefore, pre-operative planning can also be simulated using specific computer software, which allows for three-dimensional craniofacial reconstruction from computed tomography scan images [51–54, 56] (**Figures 9**–**11**). Three-dimensional finite element model analysis is also a helpful mathematical instrument for use both in orthodontics and in orthopaedics, and can determine the amount of stress, strain and displacement in the maxillofacial complex [4, 57]. However, this technique cannot be used for all patients individually due to the long elapsed

**Figure 10.** Demonstration of the surgery on the stereolithographic model, bending of the distractor plates during this

for pre-operative planning and/or stereolithographic modelling [34, 50–55].

*Stereolithographic modelling*

74 Advanced Techniques in Bone Regeneration

time for the analysis.

**Figure 9.** Stereolithographic model of our patient with UCLP.

section, and finally insertion of the bended distractor plates on the model.

The need for the correction and severity of the maxillary deficiency is the key to choose the type of osteotomy. The maxillary osteotomies can be divided into three subgroups: (1) horizontal osteotomy, for anterior advancement of the maxilla, (2) oblique osteotomy, for forward and downward movement of the maxilla, (3) step osteotomy, for children in whom canine and premolar teeth buds are in a high position [51, 58]. The standard LeFort I osteotomy and down fracturing of the maxilla are the most commonly performed osteotomies since this technique is used in older patients than those treated with RED [51, 54, 59–61]. High LeFort I and the 2–3 piece LeFort I osteotomies (this can be performed after completion of distraction, at the time of device removal) are also used with this protocol [34, 54].

After the insertion of the internal bone-borne maxillary distractors, the screws were activated for a few millimeters or more to check the correctness of the maxillary movement and to overcome premature bony contacts during the activation process [4, 34, 60–62]. Mandibular osteotomies, if needed according to the skeletal diagnosis, can be performed in the same operation [59, 60, 62].

After the operation a latency period of 3–7 days, initial activation of the internal distraction device starts. The rate of distraction is 0.5 to 1 mm per day in one or two rhythms. Activation of the distractors can be performed by the patients themselves or by the patients' parents or relatives. The planned maxillary advancement is usually obtained in several days of active distraction. The duration of the activation phase depends on the severity of the maxillary deficiency. Activation of the distractors performed until the proper overjet, overbite and relative stable posterior and anterior occlusion (overcorrected Class I molar and incisal relationship) are achieved [4, 5, 36, 51, 54, 60–62].

In early post-operative period, many clinicians use orthodontic elastic traction to control the occlusion, to prevent posterior or anterior openbite and to guide the maxilla into position [34, 59–61].

Consolidation period of 8 to 12 weeks is generally accepted in UCLP patients to prevent the risk of possible skeletal relapse [32, 51, 54, 62]. During consolidation period, bone mineraliza‐ tion of the distraction zone and bone remodelling occur according to the Ilizarov's principles.

#### *Skeletal changes (horizontal and vertical)*

The horizontal maxillary advancement usually measured as the advancement of point A ranged from 5.7 to 34 mm [34, 54, 59, 61, 62]. The average increase in SNA angle is between 5.65 and 10.8 degrees [40, 54].

The vertical changes in point A are between −1.1 mm (meaning counterclockwise rotation of the maxilla) to 7 mm (meaning clockwise rotation of the maxilla) [34, 54, 61, 62].

The counterclockwise rotation of the maxilla can be a result of inconvenient distraction force vector and can be changed by the use of the orthodontic elastic traction that can be applied between upper and lower teeth [1, 4, 34, 42].

#### *Dental changes*

The increase of the overjet ranged from 6.59 to 13.66 mm [51, 61].

**Figure 12.** Intra-oral photographs of a 21-year-old boy affected by severe maxillary hypoplasia due to unilateral cleft lip and palate treated in our clinic before internal distraction and after consolidation period (after using orthodontic elastic traction and removal).

**Figure 13.** Pre-operative and post-operative extra-oral photographs and cephalometric films of the same patient.

**Figure 14.** Intra-oral and extra-oral photographs of a 20-year-old boy affected by severe maxillary hypoplasia due to unilateral cleft lip and palate treated in our clinic before and after internal distraction osteogenesis.
