Evaluation of Platelet-rich Fibrin (PRF) Combined with Autogenous Bone in Maxillary Alveolar Clefts Reconstruction ‫تقييم الفيبرين الغنى بالصفائح الدموية ممزوجا بالعظم الذاتى فى اعادة بناء عظام‬ ‫الشق السنخى‬

Thesis submitted to: Faculty of Oral and Dental Medicine, Cairo University In partial fulfillment of the requirements of Doctorate Degree in Oral Surgery

By: Hazem Shawky Abd El-Aziz B.D.S., M.Sc. (Cairo University) 2008

Associate lecturer, Oral and Maxillofacial Surgery Department Faculty of Oral and Dental Medicine Cairo University 2012

Supervisors

Prof. Dr. Hatem Abd El-Rahman Professor in Oral and Maxillofacial Surgery Department, Faculty of Oral and Dental Medicine, Cairo University

Prof. Dr. Tarek Abbas Hassan Professor in Oral and Maxillofacial Surgery Department, Faculty of Oral and Dental Medicine, Cairo University

Dr. SAMEH AHMED SEIF Lecturer in Oral and Maxillofacial Surgery Department, Faculty of Oral and Dental medicine, Cairo University

Dedication To the soul of my father, (God bless him) My great mother, My dear wife, My two lovely daughters, and my beloved son

Acknowlgement First of all, I want to thank Allah for supporting and guiding me throughout my life.

I would like to express my deep appreciation and gratitude to Prof. Dr. Hatem Abd-al Rahman Professor of Oral and maxillofacial surgery, Faculty of Oral and Dental Medicine, Cairo University, for his kind support and encouragement. It was a great honor to work under his supervision.

My sincere gratitude and extreme thanks to Prof. Dr. Tarek

Abbas

Hassan

Professor

of

Oral

and

Maxillofacial surgery , Faculty of Oral and Dental Medicine, Cairo University, for his powerful and generous support.

Special thanks to Dr.Sameh Ahmed Seif, lecturer of Oral and Maxillofacial surgery, Faculty of oral and Dental Medicine, Cairo University, for his tolerance, cooperation and continuous encouragement. I will never forget his helpful suggestions and sincere encouragement during all the steps of this work.

I wish to express my deepest thanks to Dr. Amr Maher Professor of Anaesthesia, New Educational Dental Hospital, Cairo University, who offered his time in conducting the statistics and data analysis. I would like to express my most sincere gratitude and grateful appreciation to him for his support, encouragement and kind help.

Gratefull thanks to my dear collegue Dr Mohamed Ibrahim Faramawy lecturer of Oral and Maxillofacial surgery, Faculty of oral and Dental Medicine, Cairo University, for his cooperation and kind support.

Contents Title

Page no.

Introduction

1

Review of literature

3

Aim of the study

26

Materials & Methods

27

Results

59

Discussion

73

Summary & conclusions

83

References

85

Arabic summary

List of figures Figure no. Fig. (A):

Title Embryonic development of the face, 6th week.

Page no. 6

Fig. (1):

Showing the alveolar cleft in facial view.

32

Fig. (2):

Showing the alveolar cleft in facial view.

32

Fig. (3):

Showing the non cleft side

33

Fig. (4):

Showing maxillary occlusal view to check for palatal extension of the cleft and

33

presence of any maxillary collapse.

Showing panoramic radiograph with the Fig. (5):

arrow pointing at the alveolar cleft

34

site(after tracing). Showing 3D reconstructed image from Fig. (6):

35

the C.T. Showing the same axial cut pre and post-

Fig. (7&8):

tracing to calculate the surface area.

36

Showing the outline of the labial flap and Fig. (9):

the incision.

Showing reflection of the mucoperiosteal Fig.(10&11): flap palatally and separation of the nasal mucosa from the cleft site labially to create bed for the grafting material.

39

40

Figure no.

Title Showing

Fig.(12&13):

the

nasal

Page no.

mucosa

pushed

upwards preparing the recipient site for

41

bone grafting. Showing sutured nasal mucosa using 4/0 Fig.(14&15):

41

vicryl (arrows). Showing scoring of the periosteum at the

Fig. (16):

42

base of the labial flap. Showing the alveolar cleft defect ready

Fig.(17&18):

Showing Fig. (19):

43

for grafting incision

through

skin

and

subcutaneous tissues.

44

Showing exposure and incisions of the Fig. (20):

cartilaginous cap.

44

Showing reflection of the cartilaginous Fig. (21):

cap exposing the underlying cancellous

45

bone. Showing harvesting bone graft using Fig.(22&23):

trephine bur.

45

Fig. (24):

Harvesting of the bone graft.

46

Fig. (25):

Donor site after hervesting the bone graft.

46

Showing bone milling in bone crusher. Fig. (26-29):

46,47

Figure no.

Title

Page no.

Showing closure of the donor site wound. Fig.(30&31):

47 Showing withdrawl of the fresh blood into

Fig.(32&33):

the B.D vacutainers.

48

Showing the electeric blood centrifuge. Fig.(34&35):

49

Showing three distinct layers, Fig. (36):

a) PPP (Platelet poor plasma)

49

b) PRF (Platelet rich fibrin) c) RBC(s) (Red blood cells)

Fig.(37&38):

Showing PRF picked up from the tube cut

50

by the scissor then put on a metallic tray.

Showing PRF picked up from the tube cut Fig. (39):

by the scissor then put on a metallic tray.

51

Showing the mixture of cancellous graft Fig.(40&41):

and PRF packed into the alveolar cleft

52

defect. Showing cancellous bone graft packed Fig.(42&43):

into alveolar bone defect (group B).

53

Figure no.

Title

Page no.

Showing closure after filling the alveolar cleft Fig.(44&45): 54 defect with the bone graft. Showing small area of bare bone left after Fig. (46):

Showing Fig.(47&48):

55

sliding of the labial flap. (arrow) postoperative

healing

after

grafting with anterior iliac crest bone

60

graft. Fig.(49&50):

Showing

postoperative

grafting

from

the

healing

after

anterior

iliac

62

crest.(Group B) Showing pre and postoperative bone Fig.(51&52):

formation at the end of the follow-up

63

period.

Showing the cleft defect on the left and Fig.(53&54):

bony bridge at the clef area on the right

63

side in 3D reconstructed CT image.

Showing pre and postoperative bone Fig.(55&56):

formation at the end of the follow-up

65

period. Showing the cleft defect on the left and Fig.(57&58):

bony bridge at the cleft area on the right

65

side in 3D reconstructed CT scan. Showing measuring density of the newly Fig. (59):

formed bone.

71

List of tables Table no. Table(1):

Title Demographic characters of group A

Page no. 28

patients Table(2):

Demographic characters of group B patients

29

Table(3):

Bone Defect in group A (PRF+anterior iliac

64

crest bone graft) Table(4):

Bone Defect in group B (anterior iliac crest

66

bone graft) Table(5):

Preoperative bone defect in the two studied

67

groups

Table(6):

Postoperative bone defect in the two studied

68

groups. Table(7):

Postoperative bone volume in the two

69

studied groups. Table(8):

Percentage of the newly formed bone in

70

the two studied groups Table(9):

Mean bone density of the newly formed bone in the two studied groups.

72

List of graphs Graph no.

Title

Page no.

Graph(1):

Showing gender distribution in group A.

59

Graph(2):

Showing gender distribution in group B.

61

Graph(3):

Showing alveolar bone defect in group A.

64

Graph(4):

Showing alveolar bone defect in group B.

66

Graph(5):

Showing preoperative bone defect in both

67

groups. Graph(6):

Showing postoperative bone defect in both

68

groups. Graph(7): Showing the volume of newly formed bone in

69

both groups. Graph(8):

Showing the percentage of newly formed

70

bone in both groups. Graph(9):

Showing density of the newly formed bone in both groups..

72

Introduction

Introduction Alveolar cleft management is one of the most controversial since the first reported bone graft to the cleft maxilla is attributed to Lexer (1908), nearly a century ago. For 50 years, bone grafting was sporadic and performed without clear objectives. We have more than one philosophy and multiple treatment modalities concerning each step in alveolar cleft management regarding the need for grafting, the most appropriate age, what material is most ideal?, and should adjunctive procedures such as orthodontic expansion be used before or after grafting?, lastly, what are the appropriate measures of success?.(Peter E, et al., 2004)(Horswell BB, et al., 2003)

Alveolar cleft reconstruction is a big issue full of controversial concerning timing, graft materials, surgical techniques and methods of evaluation. For each point of which, many studies had been conducted

to

achieve

accepted

and

universal

protocol

for

management.

For many years, the autogenous bone graft was considered the main source for reconstructing the alveolar cleft defects, and multiple researchers studied different sources of autogenous bone grafts to determine the ideal source of bone graft including anterior iliac crest, calvaria, ribs, symphysis and tibial grafts. As a conclusion of all the previous studies; particulate bone graft harvested from the anterior iliac crest was considered the gold standard source for reconstructing the alveolar clefts. (Strong EB, et al., 2000) (Eppley BL, 1996) 1

Introduction

In cleft lip and palate patients, bone grafting of the alveolar cleft is necessary for rehabilitation of oral function. Among the available graft materials, autogenous bone is currently the preferred material. In some cleft patients it is difficult to augment the bone defect adequately because of the width of the gap between the maxillary segments, or as a result of bone resorption. (Marukawa E, et al., 2011) Nowadays,

numerous

studies

have

demonstrated

that

osteoinductive growth factors significantly improves bone repair. These growth factors are found in nature; therefore using platelet products raise the attractive for an adjuvant to bone healing. Since 1990s, platelet-rich plasma has been introduced for application by Marx et al., 1998 the growth factors contained within platelets in relation to their biological enhancement of bone grafts have been explored. A new family of neither fibrin glue nor a classical platelet concentrate, was called Platelet-rich fibrin (PRF), it was introduced by Dohan et al., 2006. PRF belongs to a new generation of platelet concentrates which is simply prepared without biochemical blood handling,

one

centrifugation,

and

natural

fibrin

clot

polymerization.PRP has been explored in various aspects, but there is no sufficient data upon PRF. (Choukroun J, et al., 2006)

Hence the purpose of this study was to reconstruct the maxillary alveolar clefts using PRF+ autogenous bone graft harvested from the anterior iliac crest evaluating the quantity and quality of newly formed bone.

2

Review of literature

REVIEW OF LITERATURE Cleft lip with or without cleft palate is the most prevalent congenital craniofacial birth defect in humans, observed in approximately 1 in 700 live births. In addition, cleft lip or cleft palate comprise the second most common congenital anomaly after clubfoot. (Jennifer et al., 2007)

Cleft palate occurs when the palatal shelves fail to fuse properly, and are categorized commonly according to which aspect of the palate is involved. Complete cleft palate involves both the primary and secondary palates in which no fusion between the palatal shelves or the primary palate has taken place; complete clefts are typically associated with a cleft lip. (Sadove et al., 2004)

Incomplete cleft palates can either involve the primary or the secondary palate in isolation or in combination, where fusion between the facial processes or palatal shelves has been initiated but not completed. Hence, the incomplete cleft may involve only the posterior portion of the soft palate; it may extend through the soft and hard palates to the incisive foramen, or may be limited to the alveolus. (Jennifer et al., 2007)

Clefts of the lip with or without palate (CL/P) are more often unilateral than bilateral and more common in males than in females. The unilateral defects occur more often on the left side than on the right side. Cleft palate is more common in females and more often associated with other developmental anomalies. Clefts -3-

Review of literature

may be classified as syndromic or isolated depending on the presence or absence of other developmental anomalies. (Hagberg et al., 1998) Nonsyndromic cleft lip and palate is a complex trait with a multifactorial etiology that results from a combination of genetic and environmental factors. Research to identify candidate genes and loci responsible for clefting in recent years suggests that anywhere from 3 to 14 genes contribute to cleft lip and palate. (Cobourne M.T., 2004) For nonsyndromic cleft lip and palate, candidate genes and loci have been identified on chromosomes 1, 2, 4, 6, 11, 14, 17and 19. (Blanton S.H. et al., 2004) Environmental factors that contribute to the etiology of facial clefting disorders can be divided into four groups: drugs, chemicals,

maternal

metabolic

imbalances

(as

folic

acid

deficiency) and maternal infections. Maternal exposure to alcohol and teratogenic medications such as retinoids, corticosteroids, and anti-convulsants (phenytoin and valporic acid), and folic acid deficiency during the periconceptional period can cause clefting disorders. Co-sanguinous marriages, maternal diabetes, and obesity have also been linked to an increased risk of orofacial clefts. (Eppley B.L. et al., 2005) The embryo under goes rapid changes in shape and growth between 4 and 8 weeks as the brain expands and the six branchial arches are formed. The first two branchial arches are primarily responsible for the development of the face and the cranium. The development

of

the

face

begins

from

the

neural

crest

ectomesenchyme that forms five prominences: the frontonasal

-4-

Review of literature

process

and

paired

maxillary

and

mandibular

processes

surrounding a central depression. During the 5th and 6th weeks, the bilateral maxillary processes derived from first branchial arch fuse with the medial nasal process to form the upper lip, alveolus, and primary palate. The lateral nasal process forms the alar structures of the nose. The mandibular processes form the lower lip and jaw. During the 8th week, the bilateral maxillary palatal shelves, after ascending to an appropriate position above the tongue, fuse with each other and the primary palate to form the secondary palate (Fig. A) . (Sperber G.H. et al., 2001) This

process

consequence

of

of

formation

events

such

of as

facial cell

structures

is

the

proliferation,

cell

differentiation, cell adhesion, and apoptosis. The processes of the neural crest cells are directed by molecular signals that are controlled by an array of genes. These include fibroblast growth factors (FGFs), sonic hedgehog (SHH), bone morphogenic proteins (BMPs), members of the transforming growth factor beta (TGF-b) super family, and other transcription factors. Failure or error in any of these cellular mechanisms can disrupt the fusion of the medial nasal process with the lateral nasal process and maxillary process, thus causing orofacial clefts. (Marazita M.L. et al., 2004)

-5-

Review of literature

Figure A: Embryonic development of the face, 6th week. (Avery JK. et al., 2006)

Every child born with a cleft of lip or palate should be thoroughly assessed and evaluated by assessing breathing and look for signs of airway obstruction, ability to feed, nutritional intake, weight gain and growth, concomitant anomalies (cardiac/ renal/ pulmonary/ musculoskeletal), syndromic association which require appropriate genetic testing, craniofacial examination including head shape and circumference, ears, eyes, nose, jaws, and oral cavity. (Bagheri, et al., 2012) It is important to evaluate the severity and type of cleft defect, width of cleft, position of alveolar segments and premaxilla, as well as nasal deformity, need for presurgical orthopedics and type of appliance necessary and prepare child and parents for surgical repair of cleft lip. (Bagheri, et al., 2012)

-6-

Review of literature

Classification schemes for cleft palate are usually anatomically based. This may include complete or incomplete, unilateral or bilateral, as well as the submucous cleft and bifid uvula. The primary goal of cleft palate repair is to restore the function of the palate, development of normal speech. (Bagheri et al., 2012) Clefts of the alveolar process of the maxilla inhibit the eruption and maintenance of the permanent dentition and can affect facial growth and symmetry. Alveolar bone grafting in the mixed dentition phase allows the canine teeth to migrate and erupt through the cancellous bone. Success rates with bone grafting are generally reported at 90% to 95%. (Bagheri et al., 2012) Rationale for alveolar bone grafting: The regeneration of bone and the osteogenic potential in osseous defects resulting from maxillary alveolar clefts are of great importance in terms of the restoration of jaw morphology and function. (Kawata et al., 2004) The primary objective of alveolar cleft grafting in cleft lip and palate patients is to provide bone tissue for the cleft site which will inturn allows: maxillary arch continuity, eruption of the teeth into the grafted area, closure of oronasal fistula, improves nasal symmetry,

orthodontic

movement

and

placement

of

osseointegrated implants when indicated, speech improvement, Improve oral hygiene and periodontal health and minimize growth disturbance. (Peter E. et al., 2004)

-7-

Review of literature

Placement of an autogenous bone graft into a well prepared alveolar defect site and covered with adequate and healthy mucogingival flaps will result in a united and functional maxilla. Deferring such to the mixed dentition stage when maxillary transverse growth is nearly complete will minimizethe hazards to growth stimuli. (Horswell B.B. et al., 2003) (Trindade et al., 2005) (Le B.T. et al., 2009) Moreover, grafting achieves stability of the arch and prevents collapse of the alveolar segments which provides improved orthodontic stability. (Peter E. et al., 2004) Bone grafting provides a bone matrix for eruption f teeth and support for the permanent teeth once orthodontics is completed. (Peter E. et al., 2004) providing room for the canine and lateral incisors to erupt into the arch into stable alveolar bone and maintains bony support of teeth adjacent to the cleft. (Peter E. et al., 2004) (Hynes et al., 2003) Fistulas vary in size and consequence for the cleft patient. Generally, oronasal fistulas present several challenges in cleft management: anterior nasal air escape during speech, periodontal compromise, unpleasantness to the patient, nasal sill and alar base deficiency, and, premaxillary instability in bilateral clefts. So addressing oronasal fistula may have potential benefits for both hygiene and speech through improving nasal emission and nasality. (Horswell B.B. et al., 2003) (Peter E. et al., 2004)

The nasal deformity in unilateral cleft lip and palate is a social stigma and burden to the patient, and a challenge to the surgeon. Nasal symmetry, alar bone support is an important objective in

-8-