J Oral Maxillofac Surg 65:2518-2523, 2007

Understanding Distraction Osteogenesis on the Maxillofacial Complex: A Literature Review

Maurcio Assuno Pereira, DDS,* Paulo Henrique Luiz de Freitas, DDS, Tas Frenzel da Rosa, DDS, and Cristina Braga Xavier, PhD
Management of skeletal deformities in the maxillofacial region has been an important challenge for medicine and dentistry throughout their evolution as health care sciences. Distraction osteogenesis (DO), also referred to as osteodistraction, is a surgical technique that uses the bodys own repairing mechanisms as allies for optimal tissue reconstruction. This method has gained acceptance and joined the conventional techniques for comprehensive treatment of patients with skeletal insufciencies, and its successful application in the maxillofacial complex has been extensively reported. The primary aim of this article is to summarize the information on DO, thus contributing to its study, development, and application in challenging situations of our clinical practice as oral and maxillofacial surgeons. 2007 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 65:2518-2523, 2007 The management of patients with skeletal deformities in the maxillofacial region remains an important challenge. Congenital or acquired, these deformities are invariably associated with disabilities or compromised esthetics, therefore demanding a carefully designed surgical and orthodontic treatment plan. Among the plethora of therapeutic alternatives for correcting bony defects, distraction osteogenesis (DO) is a surgical technique that uses the human bodys own repairing machinery as an ally for tissue reconstruction under a controlled approach. In DO, an osteotomy line is gradually stretched, thus promoting osteogenesis and expansion of the overlying soft tissues.1 During the past 20 years, DO has emerged as a useful alternative for the management of skeletofacial insufciencies.

Background
The history of DO begins with the old techniques of repositioning and stabilization of bone fractures used by Hippocrates.2 Bone elongation techniques were pioneered by Codivilla who, in 1905, published a case report of femoral extension using axial forces of distraction.3 Closely related to the principles of post-traumatic osseous repair and to advances in orthopedic surgery, the development of DO has received an outstanding contribution from the work of Ilizarov.4-7 The Russian surgeon developed innovative devices for skeletal xation and osteotomy techniques that deliver minimum trauma to the periosteum and to the bone marrow. His landmark set of clinical experiments led to the discovery of the biologic basis of osteodistraction, the Ilizarov effects, which suggest that gradual traction applied on living tissues can stimulate and maintain regeneration and active growth, and that the mass and shape of bones and articulations depend on their blood supply and on their functional burden.4-7 His studies later determined the technical protocols for DO, and are still used as a basic reference for studies in this eld. The application of DO in the maxillofacial complex began in 1973 with Snyders study on maxillary elongation in dogs.2-12 In 1992, for the rst time in the western literature, McCarthy et al13 reported on the clinical application of mandible elongation by gradual

*Former Professor, Oral and Maxillofacial Units II and III, Federal University of Pelotas/Dental School, Rio Grande do Sul, Brazil. Graduate Student and Resident, Oral and Maxillofacial Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. Professor, Oral and Maxillofacial Units I and II, Federal University of Pelotas/Dental School, Rio Grande do Sul, Brazil. Professor, Oral and Maxillofacial Units II and III, Federal University of Pelotas/Dental School, Rio Grande do Sul, Brazil. Address correspondence and reprint requests to Dr Pereira: Departmento de Cirurgia, Traumatologia e Prtese Buco-MaxiloFacial, Gonalves Chaves 457, CEP:96015-560, Pelotas, Rio Grande do Sul, Brazil; e-mail: maurinto@gmail.com
2007 American Association of Oral and Maxillofacial Surgeons

0278-2391/07/6512-0020$32.00/0 doi:10.1016/j.joms.2006.10.019

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2519 traction,27 as angiogenesis is of paramount importance for bone healing. Not only chemical factors but also physical factors affect the outcomes of osteodistraction. El-Hakim et al,28 in a study about the effect of electric stimulation in mandibular DO using a goat model, concluded that electric stimulation by direct charge affects distraction in a synergistic manner, provided that it is used during activation and consolidation phases. The study of Sakurakichi et al29 observed, in rabbits, the possibility of enhancing osteogenesis through ultrasound stimulation of the distraction gap, especially during the period of elongation. The results suggest that bone formed after ultrasound stimulation would feature better mechanic properties. Troulis et al30 concluded that ultrasound stimulation is a safe and noninvasive method and can be used concomitantly with DO for improving bone quality.

distraction in patients with hemifacial microsomia and Nager syndrome.3 In humans, DO has been used for surgical palatal expansion,14 mandibular symphysis elongation,15 correction of congenital facial abnormalities,1 treating of cleft patients,16 repairing of continuity defects of the mandible, alveolar crest augmentation,17 and mandible reconstruction after tumor resection.17,18 Established as a practically and scientically supported technique, DO has entered maxillofacial practices as a new tool for correcting osseous deformities while still respecting the basic principles of surgery.19,20

Biological Aspects
At histologic level, the healing process in DO differs from that of a fractures repair in 2 basic aspects: 1) it has the advantage of having a controlled microtrauma; and 2) the ossication mechanism is membranous, not endochondral.21 Understanding the molecular events that concur to osteogenesis during successful DO has important clinical implications, as it is a step toward the development of therapeutic interventions for accelerating regeneration and abbreviating consolidation time. In a review of the molecular biology of osteodistraction, Bouletreau et al22 has shown that a number of growth factors, cytokines, and extracellular matrix (ECM) proteins are involved in the processes of synthesis, mineralization, and maturation of bone tissue at the distraction gap. mRNA and protein expressions of these regulatory factors uctuate along the different stages of distraction, and applying the proper protein at the right time should optimize the outcome. For example, insulin-like growth factor-1 (IGF-1) seems to be fundamental in the early phases. Okazaki et al23 reported on the use of recombinant human broblast growth factor (FGF) at the end of the distraction period. In vitro, 24 hours of continuous cyclic mechanical stretch has led to increased mRNA levels of transforming growth factor -1, IGF-1, and FGF.24 Interleukin-6, a cytokine believed to stimulate osteoclastic resorption, was also increased in the 24 hourcycle period, which may substantiate the coupling phenomenon between bone formation and resorption25 and may reect an increase in the absolute number of osteoblasts. The different stages of bone maturation also feature a transition on the dominant type of collagen, varying from type III just after the fracture26 to type I in the late phases of bone maturation.27 Noncollagenous ECM proteins such as osteocalcin were proven to relate temporally and spatially with successful DO, and vascular endothelial growth factor expression is increased after the fracture and throughout the dis-

Technical Aspects
APPROACH TO THE DEFECT

According to Friedman and Constantino,19 a distinction must be made among the feasible possibilities of osteodistraction: Monofocal A surgical fracture creates a distraction gap (the interval between 2 bone surfaces where the healing events will happen) for posterior traction of the separated bone segments. This is the conventional approach for vertical alveolar augmentation previous to implant placement. Bifocal A solution of continuity is treated by moving a surgically produced bone segment along the defect, from one extremity to the other. The moving segment is a transport disc.31 This approach is used frequently for mandibular reconstructions after tumor ablation. Trifocal Two transport discs are created from the two extremities of defect and moved until they meet. Usually, major corrections are done with trifocal processes.32
DISTRACTION DEVICES

The gradual forces necessary to produce acceptable outcomes with DO are provided by devices called distractors, generally consisting of a bolt and nut mechanism that can be manually activated. Appliances can be purchased from a choice of reliable manufacturers, but yet special demands can alternatively be fullled with custom-made pieces. Regardless of the source, some variables determine their design33: 1) the desired vector of movement and the magnitude of skeletal correction to be accomplished;

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Table 1. BRIEF CLASSIFICATION OF DISTRACTION DEVICES USED IN ORAL AND MAXILLOFACIAL SURGERY

Relation with the skin surface2,10,11,17,33-38 External Internal Type of anchoring tissue15,17,33,35,38 Tooth-borne Bone-borne Hybrid Number of vectors of movement36 Monovectorial Multivectorial

Anchored to the distraction site by transcutaneous pins that are externally connected to the distraction device The entire mechanism is inside the oral cavity or beneath cutaneous tissues Supported only by teeth Anchored exclusively on bone tissue Fixed to both bone and teeth Provides only 1 possible direction of bone movement Bone can be distracted in 2 or more directions

Pereira et al. DO for the Maxillofacial Complex. J Oral Maxillofac Surg 2007.

2) anatomic abnormalities of the distraction site; 3) surgical access for osteotomy and placement; 4) access for activation; and 5) surgeons expectation of patient cooperation with devices activation process. In general, devices can be classied relative to position on the skin surface, the tissue on which they are anchored, and the number of force vectors they may provide to the distraction site (Table 1).
PHASES OF POSTSURGICAL TREATMENT

Ordinarily, after osteotomy and distractor xation procedures, distraction osteogenesis consists of 3 sequential phases2: 1. Latency is the period between bone division and devices activation that allows formation of a primary bone callus. Ilizarovs protocol established a latency period of 5 to 7 days, but more recent works used periods of 0 to 510,33,37,39 or 7 to 14 days.8,11,15,17,34,38 Latency duration should be set in such a way that it is not too long so as to permit calcication, and not too short so as to avoid formation of a primary osseous callus.33 The facial skeleton, because of its intramembranous origin, has a rich blood supply and benets from shorter periods of latency.3 2. Distraction is the phase in which the stretching promoted by the activated distractor stimulates tissue neo-formation at the distraction gap, in a direction parallel to the force vector. During this period, the frequency of activation and distraction rate should be judiciously applied. Ilizarov6 suggests that a distraction rate of 1 mm a day in 4 increments of 0.25 mm each offers better results. Although the majority of the authors agree with the distraction rate of 1 mm/day,4-8,10,15,17,34,38 Chin and Toth33 used a distraction rate of up to 3 mm/day and Ramchiel et al37 established a rate of 2 mm/day. Concerning the frequency of activation, 2 daily incre-

ments of 0.5 mm each seems to be the most accepted conduct.8,10,15,17,38,40 Meyer et al41 defends setting the rate on a case-by-case basis considering the many individual variables involved. The authors established a multiphase protocol considering the initial distance between bone fragments to determine the distraction rate. This protocol was successful in a study with 39 patients, with only 1 failure due to incomplete osteotomy. Block et al8 stated that the higher the daily frequency of activation is (observing a determined rate of distraction), the better the tissue responds. It has been suggested that the craniofacial skeleton may behave differently and that a risk of premature consolidation exists, especially in children. In this situation, higher frequencies can be applied.3 As Ilizarov4-7 conducted his studies using dogs endochondral long bones, there is some resistance concerning the extrapolation of his parameters into clinical application on the maxillofacial complex. The best biologic parameters for DO in the facial region remain undetermined.12,42 3. Consolidation is the period after the end of the distraction when the fragments are stabilized at an ideal position. For that to happen, the distractor is inactivated with acrylic resin or composites and then used as a rigid xation device. The length of consolidation period varies from 4 to 12 weeks,11,17,19,43 but 8 weeks seems to be sufcient for bone maturation.35 There have been reports on the use of osteoblast-like cells derived from mesenchymal cells, platelet-rich plasma, BMP-2, and growth hormones in the distraction gap, aiming at an optimization of the processes of matrix deposition and consolidation.9,44,45 Swennen et al3 suggested that longer consolidation periods are necessary when DO is applied to the mid-third of the face if compared with the mandible and other facial bones.

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2521 compared with conventional surgical techniques, on which relapse rate can reach up to 50% in large corrections. The principles of DO can, alternatively, be used after surgical-orthodontic procedures for correcting recent relapses in a noninvasive approach, and also on the correction of residual asymmetries after orthognathic surgery.52 Block and Brister35 and Block et al40 used osteodistraction as an alternative to conventional grafting for augmenting the atrophic mandible, which is limited by the risk of sensorial damage and a gain in height that is restricted by surrounding soft tissues. Chiapasco et al17 related a case of mandibular reconstruction with a revascularized bular graft followed by osteodistraction. This association seems to eliminate the disadvantages of the bular graft (eg, limited height), while preserving its advantages. An additional benet of DO was noticed: progressive lengthening escorted by adaptative changes of adjacent soft tissues, avoiding complications such as excessive tension and dehiscence. Stoelinga20 incisively criticized what he considers a cyclical phenomenon, ie, techniques and devices are presented as a revolution in the specialty, as if the previous techniques were obsolete and not worth using. As the novelty element fades away, the basic rules of surgery always prevail whereas the techniques and revolutionary devices turn into a step of the elds evolution. He states that distraction osteogenesis has been presented as a solution to all problems in oral and maxillofacial surgery, when it should be understood as an alternative to achieve a planned intermaxillary relationship, just as orthognathic surgery does. Friedman and Constantino19 point to DO as an innovative surgical technique, reliable and effective. It uses the mechanisms of the human body for healing and reconstruction, in a true tissue engineering. However, further studies are necessary, and they should address topics that are still veiled, ie, reliable ways of 3-dimensionally controlling the distraction movement. Douglas et al50 stated that modern methods of distraction have some associated complications: facial scars, undesired tooth movement, creation of diastemas, as well as difculties on device xation and on 3D movement controlling. Suhr and Kreusch42 listed as main difculties in using DO: the selection of the device, the determination of the vector of distraction, the planning of osteotomy area, and the patients cooperation. They presented data showing that only 4% of the centers actively involved with osteodistraction had used the technique in more than 100 cases and that, in these groups, the average rate of complications was 22.8%. The same authors point out that multi-vector distractions and combined procedures are at a higher risk for preoperative, intraoperative, and postoperative complications.

Discussion
Clinically, DO has its space in the management of various bone-skeletal deciencies, including reconstruction of the alveolar process for prosthetic rehabilitation,3,8,17,33 repair of continuity defects,3,31,40 mandibular lengthening,3,10,11,15,33,34 maxillary advancement,3,33,35,37,38 and treatment of sleep apnea.19 All these deformities present hard and soft tissue deciencies, and treatment with conventional techniques is extremely challenging. The main advantage of osteodistraction is its capability of promoting, at the same time, correction of bone defects and expansion of soft tissues.1,3,42-47 The tensional stress applied to bone determines adaptive changes on the adjacent soft tissues, in a process that could be appropriately named distraction histogenesis.2,3 According to Loboa et al,48 the daily tension made by the distraction device causes little trauma to the tissues, thus activating neoformation of mesenchymal tissues. With regard to this special feature of DO, Harper et al49 considered conventional techniques for correction of mandible transversal defects as being limited, for they cannot cope with the stretching of soft tissue they promote. In the same article, the authors stressed the possibility of tissue necrosis (especially at the head of mandibular condyle) when the stretching force overwhelms the adaptive ability of tissues, and reported that DO maximizes the osteogenic potential by shortening the healing period. Gradual movement is said to be less traumatic (rigid xation or bone graft are needless, and soft tissues are less manipulated), contributing to an enhanced postoperative comfort.5 Douglas et al50 note that the soft tissue covering the inferior third of the face mirrors the skeletal limits and, when an abrupt correction of the hard tissue occurs, facial esthetics may not be affected in the same proportions due to persistent soft tissue deciency. In cleft patients treated with DO, the effects on nasal projection, paranasal support, and bulging of buccinator area were believed to be more favorable compared with the traditional Le Fort I osteotomy. According to Ramchiel et al,37 DO is a more controllable and less invasive alternative for maxillary advancement, for the gradual tension simultaneously elongates muscles and adjacent soft tissues improving the overall stability of the tractioned segments. When there is a demand for great movements on conventional orthognathic surgery, there also is an increased likelihood of relapse.51 Facial soft tissues are not able to cope with the magnitude of the correction and, during the healing process, scar formation makes bone plates unstable, engendering relapse and malocclusion. In DO, the coupling of bone and soft tissue growth leads to a very low rate of relapse (7%) when

2522 Regarding the generalities on carrying out DO and choosing the distraction mechanism, Gateno et al53 proposed a software-aided protocol allowing device construction with the support of a stereolithographic model. The software also allows confection of surgical templates that simplify surgical planning, localization and placement of device, and 3D movement controlling. Placement of the device parallel to the sagittal axis of distraction and not to the bone segment is defended by Cope et al,54 thus creating forces of tension favoring osteogenesis. However, Grayson55 considered superuous the clinical problems related to the placement of the device parallel to the bone segment, the most common practice. Concerning the choice of distractors, there is a strong trend toward using internal devices,11,19,33-35,38,50,56 except when it is impossible due to anatomic reasons or case features (eg, Le Fort III maxillary advancements). Sawaki et al11 pointed to some advantages of internal devices: higher quality distraction due to the proximity between bone and the frame, the possibility of using implants as both distractors and prosthetic pillars, and a relatively unaltered social life for the patient. One of the disadvantages of internal devices is the eventual need for surgical removal.43 Douglas et al50 defend skeletal anchoring instead of tooth-borne devices, for the latter can promote undesired dental movements. Disadvantages of external distractors are mainly facial scars, increased potential of sensory damage and infections, higher incidence of distractors and supporting pins displacement, a negative psychosocial effect, and the need of special care throughout treatment, mainly in children.11,33,34,38,56 Seldin,57 however, reminds that adjustable, multivectorial external devices allow corrections and improvisation during the bone distraction. Swennen et al12 reported on self-controlled devices, which apply electronic, hydraulic, or magnetic principles. An atraumatic surgical technique is crucial. Preservation of soft tissue insertion and periosteum blood supply can be accomplished through low-energy osteotomy, or corticotomy, by using surgical burs and chisels, and fracturing bone by rotational osteoclasis.15,35,37 However, surgical complications remain. Basa et al32 related a postoperative episode of infection around the distractors support pins. The treatment employed was a combination of 7-days penicillin administration and irrigation of the wound with saline. The infection resolved without further complications, and the treatment was resumed. Rubio-Bueno et al43 reported 8 cases treated with DO and had to treat temporary paresthesia in 6 of those cases, yet having no permanent sensory losses. Temporomandibular joint symptoms were postoperative complications faced by Fukuda et al.18 The distracted bone can receive dental implants as predictably as native bone would.17,31 Bone exposi-

DO FOR THE MAXILLOFACIAL COMPLEX

tion and implant placement are recommended 10 to 16 weeks after the end of the activation period.1 Dual purpose devices, which are distractors and implants at the same time, simplify the procedure and reduce chair time.58-61 DO can even be used for repositioning misplaced implants.42 Despite a number of articles discussing the applications of DO and establishing this method as a reliable and evidence-based treatment alternative, important parameters like appropriate age for treatment, optimal rate and frequency, length of latency, and stabilization periods are yet to be consensually determined. The distinctive advantage of the technique is its capacity to promote neoformation of hard and soft tissues; yet, some clinical drawbacks must be assessed so as to promote DO to the post of gold standard when treatment of bone discontinuity is regarded. Still, additional scientic effort is needed for general acceptance of this method by maxillofacial surgeons.

References
1. Chin M: Distraction osteogenesis in maxillofacial surgery, in Lynch SE, Genco RJ, Marx RE (eds): Tissue Engineering: Applications in Maxillofacial Surgery and Periodontics. Carol Stream, Quintessence, 1999, pp 147-159 2. Samchukov ML, Cherkashin AM, Cope JB: Distraction osteogenesis: history and biologic basis of new bone formation, in Lynch SE, Genco RJ, Marx RE (eds): Tissue Engineering: Applications in Maxillofacial Surgery and Periodontics. Carol Stream, Quintessence, 1999, pp 131-146 3. Swennen G, Schliephake H, Dempf R, et al: Craniofacial distraction osteogenesis: a review of the literature. Part 1: Clinical studies. J Oral Maxillofac Surg 30:89, 2001 4. Ilizarov GA: The principles of the Ilizarov method. Bull Hosp Joint Dis Orthop Inst 48:1, 1988 5. Ilizarov GA: The tension-stress effect on the genesis and growth of tissues. Part I: The inuence of stability of xation and soft-tissue preservation. Clin Orthop 238:249, 1989 6. Ilizarov GA: The tension-stress effect on the genesis and growth of tissues. Part II: The inuence of the rate and frequency of distraction. Clin Orthop 239:263, 1989 7. Ilizarov GA: Clinical application of the tension-stress effect for limb lengthening. Clin Orthop Rel Res 250:8, 1990 8. Block MS, Chang A, Crawford C: Mandibular alveolar ridge augmentation in the dog using distraction osteogenesis. J Oral Maxillofac Surg 54:309, 1996 9. Cho BC, Kim JY, Lee JH, et al: The bone regenerative effect of chitosan microsphere-encapsulated growth hormone on bony consolidation in mandibular distraction osteogenesis in a dog model. J Craniofac Surg 15:299, 2004 10. Karaharju-Suvanto T, Peltonen J, Kahri A, et al: Distraction osteogenesis of the mandible: An experimental study on sheep. J Oral Maxillofac Surg 21:118, 1992 11. Sawaki Y, Ohkubo H, Hibi H, et al: Mandibular lengthening by distraction osteogenesis of the mandible using osseointegrated implants and an intraoral device: A preliminary report. J Oral Maxillofac Surg 54:594, 1996 12. Swennen G, Dempf R, Schierle H: Craniofacial distraction osteogenesis: A review of the literature. Part 2: Experimental studies. J Oral Maxillofac Surg 31:123, 2002 13. McCarthy JG, Schreiber J, Karp N, et al: Lengthening the human mandible by gradual distraction. Plast Reconstr Surg 89:1, 1992 14. Bell WH, Epker BN: Surgical orthodontic expansion of the maxilla. Am J Orthod 70:517, 1976

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15. Bell WH, Harper RP, Gonzalez M, et al: Distraction osteogenesis to widen the mandible. Br J Maxillofac Surg 35:41, 1997 16. Ko EWC, Figueroa AA, Polley JW: Maxillary advancement with distraction osteogenesis by use of a rigid external distraction device: A 1-year follow up. J Oral Maxillofac Surg 58:959, 2000 17. Chiapasco M, Brusai R, Galioto S: Distraction osteogenesis of a bular revascularized ap for improvement of oral implant positioning in a tumor patient: A case report. J Oral Maxillofac Surg 58:1434, 2000 18. Fukuda M, Iino M, Yamaoka K, et al: Two-stage distraction osteogenesis for mandibular segmental defect. J Oral Maxillofac Surg 62:1164, 2004 19. Friedman CD, Constantino PD: Use of distraction osteogenesis for maxillary advancement: Preliminary results (Discussion). J Oral Maxillofac Surg 52:287, 1994 20. Stoelinga PJ: Distraction from the ground rules? Int J Oral Maxillofac Sur 27:414, 1998 21. Yates KE, Troulis MJ, Kaban LB, et al: IGF-I, TGF- , and BMP-4 are expressed during distraction osteogenesis of the pig mandible. Int J Oral Maxillofac Surg 31:173, 2002 22. Bouletreau PJ, Warren SM, Longaker MT: The molecular biology of distraction osteogenesis. J Craniomaxillofac Surg 30:1, 2002 23. Okazaki H, Kurokawa T, Nakamura K, et al: Stimulation of bone formation by recombinant broblast growth factor-2 in callotasis bone lengthening of rabbits. Calcif Tissue Int 64:542, 1999 24. Cillo JE Jr, Gassner R, Koepsel RR, et al: Growth factor and cytokine gene expression in mechanically strained human osteoblast-like cells: Implications for distraction osteogenesis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 90:147, 2000 25. Lane JM, Suda M, Von Der Mark K, et al: Immunouorescent localization of structural collagen types in endochondral fracture repair. J Orthop Res 4:318, 1986 26. Lane JM, Hurson B, Boland PJ, et al: Osteogenic sarcoma. Clin Orthop Relat Res 204:93, 1986 27. Warren SM, Mehrara BJ, Steinbrech DS, et al: Rat mandibular distraction osteogenesis: Part III. Gradual distraction versus acute lengthening. Plast Reconstr Surg 107:441, 2001 28. El-Hakim IE, Azim MA, El-Hassan FA, et al: Preliminary investigation into the effects of electrical stimulation on mandibular distraction osteogenesis in goats. Int J Oral Maxillofac Surg 33:42, 2004 29. Sakurakichi K, Tsuchiya H, Uehara K, et al: Effects of timing of low-intensity pulsed ultrasound on distraction osteogenesis. J Orthop Res 22:395, 2004 30. Troulis MJ, Coppe C, ONeill MJ, et al: Ultrasound: Assessment of the distraction osteogenesis wound in patients undergoing mandibular lengthening. J Oral Maxillofac Surg 61:1144, 2003 31. Block MS, Almerico B, Crawford C, et al: Bone response to functioning implants in dog mandibular alveolar ridges augmented with distraction osteogenesis. Int J Oral Maxillofac Implants 13:342, 1998 32. Basa S, Uner E, Citir M, et al: Reconstruction of a large mandibular defect by distraction osteogenesis: A case report. J Oral Maxillofac Surg 58:1425, 2000 33. Chin M, Toth BA: Distraction osteogenesis in maxillofacial surgery using internal devices: Review of ve cases. J Oral Maxillofac Surg 54:45, 1996 34. Altuna G, Walker DA, Freeman E: Rapid orthopedic lengthening of the mandible in primates by sagittal split osteotomy and distraction osteogenesis: A pilot study. Int J Adult Orthod Orthognath Surg 10:59, 1995 35. Block MS, Brister GD: Use of distraction osteogenesis for maxillary advancement: Preliminary results. J Oral Maxillofac Surg 52:282, 1994 36. Manganello LC, Silveira ME, Guerra MC: Expanso mandibular (distrao mandibular), in Souza LCM, Silveira ME, Cappellette M, et al (eds): Cirurgia ortogntica e ortodontia. So Paulo, Brazil, Santos, 1998, pp 205-211 37. Rachmiel A, Jackson IT, Potparic Z, et al: Midface advancement in sheep by gradual distraction: A 1-year follow-up study. J Oral Maxillofac Surg 53:525, 1995 38. Yamamoto H, Sawaki Y, Ohkubo H, et al: Maxillary advancement by distraction osteogenesis using osseointegrated implants. J Craniomaxillofac Surg 25:186, 1997

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39. Troulis MJ: Effects of latency period in mandibular distraction osteogenesis (Discussion). Int J Oral Maxillofac Surg 32:63, 2003 40. Block MS, Otten J, McLaurin D, et al: Bifocal distraction osteogenesis for mandibular defect healing: Case reports. J Oral Maxillofac Surg 54:1365, 1996 41. Meyer U, Kleinheinz J, Joos U: Biomechanical and clinical implications of distraction osteogenesis in craniofacial surgery. J Craniomaxillofac Surg 32:140, 2004 42. Suhr MAA, Kreusch TH: Technical considerations in distraction osteogenesis. Int J Oral Maxillofac Surg 33:89, 2004 43. Rubio-Bueno P, Padrn A, Villa E, et al: Distraction osteogenesis of the ascending ramus for mandibular hypoplasia using extraoral or intraoral devices: A report of 8 cases. J Oral Maxillofac Surg 58:593, 2000 44. Ashinoff RL, Cetrulo CL Jr, Galiano RD, et al: Bone morphogenic protein-2 gene therapy for mandibular distraction osteogenesis. Ann Plast Surg 52:585, 2004 45. Kitoh H, Kitakoji T, Tsuchiya H, et al: Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesisa preliminary result of three cases. Bone 35:892, 2004 46. Gaggl A, Schultes G, Regauer S, et al: Healing process after alveolar ridge distraction in sheep. Oral Surg Oral Med Oral Pathol 90:420, 2000 47. Yonehara Y, Takato T, Susami T: Correction of micrognathia attributable to ankylosis of the temporomandibular joint using a gradual distraction technique: Case report. J Oral Maxillofac Surg 58:1415, 2000 48. Loboa EG, Fang TD, Warren SM, et al: Mechanobiology of mandibular distraction osteogenesis: Experimental analyses with a rat model. Bone 34:336, 2004 49. Harper RP, Bell WH, Hinton RJ, et al: Reactive changes in the temporomandibular joint after mandibular midline osteodistraction. Br J Maxillofac Surg 35:20, 1997 50. Douglas LR, Douglas JB, Smith PJ: Intraoral mandibular distraction osteogenesis in patient with severe micrognathia secondary to TMJ ankylosis using a tooth and bone-anchored device (PIT device): A case report. J Oral Maxillofac Surg 58:1429, 2000 51. Drew SJ: Maxillary advancement with distraction osteogenesis by use of a rigid external distraction device: A 1-year follow-up (Discussion). J Oral Maxillofac Surg 58:969, 2000 52. Uckan S, Buchbinder D, Orban M, et al: Management of early relapse after a sagittal split ramus osteotomy by gradual callus distraction: A case report. J Oral Maxillofac Surg 58:220, 2000 53. Gateno J, Allen ME, Teichgraeber JF, et al: An in vitro study of the accuracy of a new protocol for planning distraction osteogenesis of the mandible. J Oral Maxillofac Surg 58:985, 2000 54. Cope JB, Yamashita J, Healy S, et al: Force level and strain patterns during bilateral mandibular osteodistraction. J Oral Maxillofac Surg 58:171, 2000 55. Grayson B: Force level and strain patterns during bilateral mandibular osteodistraction (Discussion). J Oral Maxillofac Surg 58:171, 2000 56. Douglas LR, Douglas JB, Nakeeb S, et al: Intraoral distraction osteogenesis in the baboon mandible using a tooth and boneanchored appliance. J Oral Maxillofac Surg 58:49, 2000 57. Seldin EB: An in vitro study of the accuracy of a new protocol for planning distraction osteogenesis of the mandible (Discussion). J Oral Maxillofac Surg 58:985, 2000 58. Gaggl A, Schultes G, Krcher H: Distraction implants. A new possibility for augmentative treatment of the edentulous atrophic mandible: A case report. Br J Oral Maxillofac Surg 37:481, 1999 59. Gaggl A, Schultes G, Krcher H: Distraction implants. A new operative technique for alveolar ridge augmentation. J Craniomaxillofac Surg 27:214, 1999 60. Gaggl A, Schultes G, Rainer H, et al: The trans gingival approach for placement of distraction implants. J Oral Maxillofac Surg 60:793, 2002 61. Klein C, Papageorge M, Kovcs A, et al: Initial experiences using a new implant based distraction system for alveolar ridge augmentation. J Oral Maxillofac Surg 30:167, 2001