1 INTRODUCTION Cleft lip and palate are common birth defects in Vietnam and the world. Globally, the proportion of newborns suffering from this type of disability ranges from 1/750 - 1/1000, particularly on the geographical area and socio-economic conditions in that region. In Vietnam, this ratio is about 1/1000 - 2/1000. Children with cleft lip and palate suffer from abnormal changes, locally or generally, anotomy or functions, psychologicalyl or physiologically. Among them, the anatomical changes directly affect the tooth formation and eruption in the cleft area, leading to missing or displaced teeth, crowded teeth. As a result, the patient will experience changes in the occlusion, chewing function, and as a result, the child will get choke while eating or drinking, suffer from respiratory diseases, hearing and pronunciation disorders, These things greatly affect the psychology of children, they become guilty, inferiority and alienation from the community. Treatment of cleft lip and palate patients requires the coordination of specialized doctors, including: plastic surgeon, anesthesiologist, orthodontist, pediatrician , ENT specialists, linguistics and psychologist, with a combination of therapies and techniques for a long time. In which, plastic surgery for closing the gap is the first and most basic treatment Along with surgery for the cleft lip and palate, the bone grafting for the alveolar cleft is also a necessary treatment. Alveolar bone graft helps to close the cleft of the jawbone, restores anatomical morphology of the dental arch, makes the anterior border of maxillary uninterrupted, closes the fistula (if exsist). Thereby stimulating tooth eruption in the cleft area, creating a full bone volume for orthodontic treatment and restoring the missing teeth on the cleft, making the nostrils in the cleft side more aesthetic. For alveolar cleft graft, most surgeons have used autologous grafts harvested from the skull, the tibia, the mandible, the iliac crest. In addition, with the development of biotmaterial, clinicians also usedt autologous bone graft in combination with growth factors and achieved promising results. In Vietnam, a number of studies on autologous bone grafting into the alveolar cleft have been published, however, no studies have evaluated the effectiveness of combining autologous bone with growth factors. Therefore, we conduct this research with 2 goals: 1. To describe the alveolar cleft with clinical and radiographic features in patients with cleft lip and palate . 2. To evaluate the bone resorption when using iliac bone, with platelet-rich plasma and bone substitutes.
1 INTRODUCTION Cleft lip and palate are common birth defects in Vietnam and the world Globally, the proportion of newborns suffering from this type of disability ranges from 1/750 - 1/1000, particularly on the geographical area and socio-economic conditions in that region In Vietnam, this ratio is about 1/1000 - 2/1000 Children with cleft lip and palate suffer from abnormal changes, locally or generally, anotomy or functions, psychologicalyl or physiologically Among them, the anatomical changes directly affect the tooth formation and eruption in the cleft area, leading to missing or displaced teeth, crowded teeth As a result, the patient will experience changes in the occlusion, chewing function, and as a result, the child will get choke while eating or drinking, suffer from respiratory diseases, hearing and pronunciation disorders, These things greatly affect the psychology of children, they become guilty, inferiority and alienation from the community Treatment of cleft lip and palate patients requires the coordination of specialized doctors, including: plastic surgeon, anesthesiologist, orthodontist, pediatrician , ENT specialists, linguistics and psychologist, with a combination of therapies and techniques for a long time In which, plastic surgery for closing the gap is the first and most basic treatment Along with surgery for the cleft lip and palate, the bone grafting for the alveolar cleft is also a necessary treatment Alveolar bone graft helps to close the cleft of the jawbone, restores anatomical morphology of the dental arch, makes the anterior border of maxillary uninterrupted, closes the fistula (if exsist) Thereby stimulating tooth eruption in the cleft area, creating a full bone volume for orthodontic treatment and restoring the missing teeth on the cleft, making the nostrils in the cleft side more aesthetic For alveolar cleft graft, most surgeons have used autologous grafts harvested from the skull, the tibia, the mandible, the iliac crest In addition, with the development of biotmaterial, clinicians also usedt autologous bone graft in combination with growth factors and achieved promising results In Vietnam, a number of studies on autologous bone grafting into the alveolar cleft have been published, however, no studies have evaluated the effectiveness of combining autologous bone with growth factors Therefore, we conduct this research with goals: To describe the alveolar cleft with clinical and radiographic features in patients with cleft lip and palate To evaluate the bone resorption when using iliac bone, with platelet-rich plasma and bone substitutes 2 LITERATURE REVIEW 1.1 ANATOMY OF THE LIP AN PALATE 1.1.1 Lip: The structures that surround the oral aperture In the central region their superior border corresponds to the inferior margin of the base of the nose Laterally, their limits follow the alar sulci and the upper and lower lips join at the oral commissures The inferior limit of the lips in the central region is the mentolabial sulcus 1.1.2 Palate: The palate divides the nasal cavity and the oral cavity, with the hard palate positioned anteriorly and the soft palate posteriorly The soft palate is distinguished from the hard palate at the front of the mouth in that it does not contain bone 1.1.3 Maxillary alveolar bone anatomy: The maxillary alveolar bone is part of the lower edge of the maxillary bone and forms the upper dental arch Its front limit is the upper lip The oral mucosa covers its outer and inner surface , in the middle there is dental arch Alveolar bone connects to the ligament around the tooth, and root The dental arch is a part of the maxillary that has a curved shape without interruption The dental arch is covered by a attached and mobile gingival epithelium, which supports the temporary and permanent teeth There are also permanent tooth germs in the bone structure When the cleft palate appears, there is disruption of the bone structure and covering gingival epithelium The change in anatomical morphology leads to a change in the arrangement of teeth in the dental arch or an abnormal position, or number of permanent tooth germs in the cleft area 1.2 CLASSIFICATION OF CLEFT LIP AND PALATE Pfeiffer (Germany) has created diagram about the classification of cleft lips and palate In 1971, Kernahan introduced a Y-diagram to describe his classification In 1976, Millard modified the Kamahan diagram and considered it as a new classification, named “Striped Y” 1.3 CÁC ANATOMIC ABNORMALIES IN CLEFT LIP AND PALATE PATIENTS Anatomic abnormalies in lip and nose Anatomic abnormalies in palate Changes in muscle system The pre-maxillary at both sides aren‟t connected to the poseterior area of the maxillary Anatomic abnormalies exsisted in the dental arch The cartilage on the affected side still does not achieve the necessary proportion 3 Erupting disorders still exist, along with malocclusion 1.4 HEALING MECHANISM OF THE GRAFT Bone resorption and bone regeneration are two main and simultaneous activities Early resorption is primarily caused by immune cells, which provide conditions for healing, and produce factors that cause bone resorption The bone regeneration is mainly stimulated by undifferentiated osteocytic cells and mesenchymal cells from neovascular vessels 1.5 PLATELET-RICH PLASMA (PRP) PRP is extracted from autogolous blood, with a high-concentration of platelet It contains many important growth factors, such as PDGF, TGF-B1, TGF-B2, EGF which take important roles in healing and bone regeneration 1.6 GRAFTING MATERIAL There are types of grafting materials: - Autologous bone - Allograft - Xenograft - Alloplastic grafts 1.6.1 Autologous (or autogenous) bone: involves utilizing bone obtained from the same individual receiving the graft Bone can be harvested from non-essential bones, such as from the iliac crest, or more commonly in oral and maxillofacial surgery, from the mandibular symphysis (chin area) or anterior mandibular ramus (the coronoid process); this is particularly true for block grafts, in which a small block of bone is placed whole in the area being grafted When a block graft will be performed, autogenous bone is the most preferred because there is less risk of the graft rejection because the graft originated from the patient's own body.[4] As indicated in the chart above, such a graft would be osteoinductive and osteogenic, as well as osteoconductive A negative aspect of autologous grafts is that an additional surgical site is required, in effect adding another potential location for post-operative pain and complications 1.6.2 Allograft: Allograft bone, like autogenous bone, is derived from humans; the difference is that allograft is harvested from an individual other than the one receiving the graft Allograft bone can be taken from cadavers that have donated their bone so that it can be used for living people who are in need of it; it is typically sourced from a bone bank Bone banks also supply allograft bone sourced from living human bone donors (usually hospital inpatients) who are undergoing elective total hip arthroplasty (total hip replacement surgery) During total hip replacement, the orthopaedic surgeon removes the patient's femoral head, as a necessary part of the process of inserting the artificial hip prosthesis The femoral head is a roughly spherical area of bone, located at the proximal end of the femur, with a diameter of 45 mm to 56 mm in adult humans The patient's femoral head is most frequently discarded to hospital waste at the end of the surgical procedure However, if a patient satisfies a number of stringent regulatory, medical and social history criteria, and provides informed consent, their femoral head may be deposited in the hospital's bone bank 1.6.3 Alloplastic grafts: An alloplastic graft is composed of material that is not taken from an animal or human source Alloplastic grafts can be derived from natural sources (such as an elements or minerals), synthetic (man-made) substances, or a combination of the two One reason many dentists prefer alloplastic grafts is that they not require tissue to be harvested from another source Alloplastic grafts can be made of hydroxyapatite (HA), calcium carbonate, and tricalcium phosphate Hydroxyapatite is the most frequently used due to its strength, durability, and ability to integrate well with bone In fact, a large percentage of human bone is composed of a form of hydroxyapatite Calcium carbonate is becoming less popular because it tends to resorb more quickly and make the bone susceptible to breakage 1.6.4 Xenograft: Tissue or organs from an individual of one species transplanted into or grafted onto an organism of another species, genus, or family They binds well to the bone in the receiving area, but its slow resorptions rate can have negative effects on the newly formed bone, thus affecting clinical outcomes Due to the prevalence of other types of bone grafting, less common bone species is used, and because of the risk of causing immune reactions, this material is quite limited 1.7 BONE RESORPTION AFTER ALVEOLAR GRAFTING World literature describes the failure rate of iliac bone graft in patients with cleft palate and some data related to bone resorption process after grafting Kinderland was the first author to come up with the idea of assessing bone resorption level, he created a scale of levels as follows: - Grade I: Bone resorption from -25% - Grade II: Bone resorption from 25 - 50% - Grade III: Bone resorption from 50 - 75% - Grade IV: Bone resorption from 75 - 100% Bone resorption at levels I and II is considered a successful bone graft surgery Bone resorption at levels III and IV is considered a failed surgery Success rates for bone grafting in medicine are also diverse In cases of bone grafting before canine eruption, the success rate is about 72% to 90%, while in bone grafting after canines eruption, the rate is about 67% to 85% Kinderland and his colleagues performed bone grafting for 38 patients at the time the canine teeth had erupted and the success rate was 73% The success rate in the Newland study was nearly 90% with 72 patients Filho also achieved a 72% success rate in his study of 50 patients who had surgery before the canine teeth had erupted Factors such as: the time of surgery before or after the canine erupt, the degree of tooth formation or the orthodontic treatment after bone grafting should be carefully considered so that the bone graft results are as expected 1.8 TIME FOR ALVEOLAR GRAFTING The optimal age for alveolar bone grafting after cleft lip and palate repair is still controversial.The development of the vertical and horizontal upper jaw bone is nearly completed by the age of 8, and then the maxilla develops vertically by the addition of the alveolar bone Along with the reason that the age of the lateral incisors eruption is usually at the age of to years old, by the time the children aged to 11 years old canine erupt 1/4 to ½ At the age of 11 to 12, dentists and plastic surgeons advocate for alveolar bone grafting later in the mixed tooth period when children are to 12 years old However, alveolar bone graft surgery is still conducted later than 12 years old with the purpose of supporting orthodontic and prosthetic prosthesis 1.9 HISTORY OF ALVEOLAR GRAFTING Since 1908 Lexer has tried grafting alveolar bone in the alveolar cleft, at the same time with cleft lip repair But it was not until 1914 that Drachter published the first report on the success of the alveolar bone graft using the tibia bone in cleft and palate patients By 1931, Veau also performed the first alveolar cleft graft with lip repair in one phase But also from 1959, Ritter was the first to issue a warning about the underdevelopment of the maxilla caused by alveolar bone graft Pruzansky (1964) frankly criticized the first alveolar bone grafting in cleft lip and palate patients, based on his research that he suggested that alveolar bone grafting should be done after cleft lip and palate repair, and until mixed teeth Bjork and Skieller (1974) show that the vertical and horizontal development of the maxilla is nearly accomplished by the age of 8, and most of the subsequent development of the maxilla follows vertically by the growing of the alveolar bone teeth, plastic surgeons advocating for alveolar bone grafting are as follows: after the child has been cleft lip and palate repaired, at the time of the child over years old, when they have mixed teeth Since then, there have been many reports in the world about the success and effectiveness of alveolar bone grafting in cleft lip and palate patients Boyne and Sands (1976) in their report stated that alveolar bone grafting should be performed at the early stage of mixed teeth, when the child is aged 7-11 years old, after lip and arch shaping A report by Abyholm et al (1982) showed that the alveolar bone graft after lip and palate surgery in the early stage of mixed teeth of children, when children aged 7-11 years, that is the age lateral incisors and canines erupt, will stimulate the formation of root teeth and the growth of these teeth In Vietnam from 2009 to 2012, three studies have been published on this issue: Nguyen Manh Ha (2009) "Evaluating the effectiveness of alveolar bone graft surgery using iliac bone in patients after cleft lip and palate repain." Nguyen Huu Nam (2011), "Research using porous bone graft from the tibia to treat alveolar bone defects in patients with congenital cleft palate"; Vo Van Nhan (2012), "Studying implant transplantation in patients who received jaw bone implants after surgery to create full cleft lip and palate" Along with the development of science and biotechnology, researchers have successfully applied clinically when using growth factors and biological materials in general bone graft and cleft palate graft in particular to increase bone mass gained after healing It should be noted in the studies of: Maria Nagata et al (2008), Giuseppe Intini (2009), Altaf H (2013) and many other studies MATERIALS AND METHODS 2.1 SUBJECTS The subjects of the study were all patients who had cleft lip and palate repair, referred at the Odonto-Stomatology Hospital - Central Hospital and Hanoi Medical University Hospital , wishing to have alveolar bone graft surgery Inclusion criteria: The patient, regardless of gender, years of age or older He or she has had cleft lip and palate repair 7 Patients who received orthodontic treatment months prior to surgery Patients and their families agreed to participate in this study Exclusion criteria: We exclude patients who have had cleft lip and palate repair but not have alveolar cleft Patients who are not receiving orthodontic treatment prior to the surgery Patients with compromised medical condition Patients whose medical records are not completed Patients who not agree to participate in the study 2.2 METHODOLOGY 2.2.1 Study design This study was designed as a controlled clinical trial Study objectives: To describe the clinical features of alveolar cleft and their relationship with other aspects To compare the outcome of bone grafting between groups: Group using iliac bone graft with combination of bone substitutes and platelet-rich plasma Group using iliac bone alone 2.2.2 Sample size The study included groups, 20 patients were recruited in each group, with the total of 40 patients The patients were recruited from September, 2013 to September, 2017 2.2.3 Data collecting According to the designed record, including: Patient interviews, clinical and subclinical examination indicators (X-ray, CBCT) CT-Conbeam film is used to evaluate the bony structure on both sides of the cleft, including the width and height of the cleft palate, before and after the bone graft surgery As well as monitoring the eruption of teeth which have not yet erupted into the bone graft area after surgery To measure the height of the cleft : h1 + h2 To measure width of the cleft : H =the w1 + w2 W = 2.2.4 Patient follow-up The patient was clinically monitored postoperatively until discharge (7 to l0 days) Clinical examination, X-ray for evaluation after days, months, months and after one year post-operatively 2.2.5 Evaluating scale Good: the grafting is good, no pus leakage, bone is not discharged, patients with nasal fistula have been closed, the volume of bone graft is still sufficient and restores the morphology of the maxillary, X-ray showed that the bone graft was not discharged, the bone was good around the gap Bad: The grafting has pus leak, graft bone is eliminated, patients still have nasopharyngeal fistula (eating, drinking food, water through the nose), X-ray shows bone graft is partially or completely resorbed) The closure of the nasal fistula: the patient no longer has food or drink through the nose while drinking or eating Physical examination showed that the fistula was closed Canine eruption into the grafting area By clinical examination and X-ray Calculated by the distance from the edge of incisor to the alveolar bone Bone resorption: It is assessed by measuring the height of the alveolar bone in the grafted area, at a certain position, by CT - Cone beam At the time after months of surgery o Height measurement position: determined at the line between the maxillary cleft (where the bone has been grafted), from the side of adjacent teeth, with the height measured from the arch of the maxillary bone by the base of the nose to the ridge of the jaw o Bone resorption level was calculated by comparing height (H) measured before surgery (height to be compensated), and height measured at months after surgery o Comparison of bone resorption level between simple iliac crest bone grafting method with iliac crest + PRP + bone substitutes 2.2.6 Statistically analyses After collecting the data We analyzed data using SPSS 16.0 : Statistical test is used to determine the difference between age groups, gender, whether or not the nasal fistula is present, the parameters measured before and after surgery Study variables are presented in the percentage and average value Research results are presented in the form of a single table, double tables and appropriate charts Errors and errors prevention: Use medical record form The information is consistent and clear 9 2.2.7 Time and location of the trial The trial is studied in the Department of Maxillofacial Surgery, Hanoi National Hospital of Odonto-Stomatology, from Sep, 2013 to Sep, 2017 2.2.8 Ethical approval The research proposal was approved by the Council for Graduating study of the Faculty of Odonto-Stomatology - Hanoi Medical University to ensure scientific research The research protocol was approved by the Scientific Council of Hanoi Central Odonto-Stomatology Hospital to conduct research at the Hospital 2.3 SURGERY PROTOCOL 2.3.1 Indications and contra-indications Indications: All patients aged more than years old, healthy enough for general anesthesia, no systemic disease which may lead to complications during surgery Had cleft lip and palate repair There is a gap or missing bone in the alveolus No infection or pathologic conditions in oral cavity No pathologic conditions or anatomic abnomalies in the donor site Contra-indications: Compromised medical status that will not allow for general anesthesia Infection or pathologic condition at the alveolar cleft Anatomic anomalies or pathologic condition at the donnor site 2.3.2 Pre-operation preparation Oral hygience, tooth treatment General examination the day before surgery 2.3.3 Anesthesia : General anesthesia 2.3.4 Alveolar cleft grafting procedure : Step : Local anesthesia Step : Mucosal incision, open the flap Step : Elevator the full flap Step : Suture the base flap to contain the graft Step : Grafting Step : Flap retention Step : Suturing 10 2.3.5 Bone harvesting from iliac bone procedures : Make the incision in the center and through the full thickness of the skin, , on the iliac crest Dissect the muscle to expose the periosteum of the iliac crest Make the meningeal incision, three-sided periosteal dissection: internal, anterior, posterior aspect of the iliac crest Cut the bone, across the iliac crest in three directions: inside, before, after Next, harvest the iliac crest from the inside Use bone drill or small chisel to make pourous hole in the iliac graft Harvest the graft with both cortical and purous bone Keep the graft in the cup with warm sterile saline Suturing the muscle and put a drainage at the iliac site, suturing the donor site 2.3.6 Platelet-rich plasma extraction : Obtain WB by venipuncture in acid citrate dextrose (ACD) tubes Do not chill the blood at any time before or during platelet separation Centrifuge the blood using a „soft‟ spin Transfer the supernatant plasma containing platelets into another sterile tube (without anticoagulant) Centrifuge tube at a higher speed (a hard spin) to obtain a platelet concentrate The lower 1/3rd is PRP and upper 2/3rd is platelet-poor plasma (PPP) At the bottom of the tube, platelet pellets are formed Remove PPP and suspend the platelet pellets in a minimum quantity of plasma (2-4 mL) by gently shaking the tube 2.3.7 Preparation of combined graft with bone substitutes, iliac bone and PRP Make a bone graft, which is a bone mass, including the cortical and porous bone Bone mass is equal to the height of the cleft The horizontal width should be sufficient to compensate for the lack of bone in the gap Mix platelet-rich plasma, with porous bone and bone substitutes Carry out bone grafting techniques such as standard technical procedures 2.3.8 Post-operative care: Local and general care 11 RESULTS 3.1 PRE-OPERATIVE FEATURES Table 3.1: Age Group Group Group Age group n % n % 12 40,0 10 33,3 8-12 y 18 60 20 66.7 Above 12 y Total 30 100 30 100 (p>0,05, Chi-square test) p 0,592 0,359 20 18 20 Total n % 22 36,7 38 63.3 60 100 12 10 10 8-12t >12t >12t 8-12t Group Group Chart 3.1: Age distribution Table 3.2: Gender Group Group Group Gender n % n % Male 10 33,3 16 53,3 Female 20 66,7 14 46,7 Total 30 100 30 100 (p>0,05, Chi-square test) Total n % 26 43,3 34 56,7 60 100 20 20 16 14 Male 10 Female 10 Female Male Group Group Chart 3.2: Gender distribution p 0,118 12 Table 3.3: Types of cleft Group Group Types n % n % Unilateral 25 83,3 23 76,7 Bilateral 16,7 23,3 Total 30 100 30 100 Total of clefts 35 37 (p>0,05, Chi-square test) Group Total n % 48 80,0 12 20,0 60 100 p 0,519 Group 30 25 23 Group 20 10 Unilaterl Bilateral Chart 3.3: Distribution of cleft types Table 3.4: Distribution of cleft side Group Group Group Total p Side n % n % n % Right 18 51,4 14 37,8 32 44,4 0,246 Left 17 48,6 23 62,2 40 55,6 Total 35 100 37 100 72 100 (p>0,05, Chi-square test) Table 3.5: Existence of oro-nasal fistula Group Group Total p Group n % n % n % Oronasal fistula Existed 24 80 25 83,3 49 81,6 0,536 No exsited 20 16,7 11 18,4 Total 30 100 30 100 60 100 (p>0,05, Chi-square test) 13 25 Group no existed existed 24 Group 10 20 30 Chart 3.4: Oro-nasal fistula distribution Table 3.6: Development and eruption of canine Group Group Group Total Canine n 16 17 35* % n % 5,7 8,1 45,7 18 48,6 48,6 16 43,3 100 37* 100 n 34 33 72 % 0,336 32 60 100 Non - existed Existed - Unerupted Existed - Erupted Total (p>0,05, Chi-square test) Table 3.7: Development and eruption of canine by age Age 8-12 >12 Total Canine n % n % n % No existed Unerupted Group Erupted Total No existed Unerupted Group Erupted Total (p>0,05, Chi-square test) 2,85 12 34,28 0 17 11 16 2,70 29,72 p p 2,85 2* 5,7 11,42 16* 45,7 0,238 48,6 17* 48,6 35 100 5,40 3* 8,1 18,91 18* 48,6 0,296 27,02 16* 43,2 37 100 14 Table 3.8 Pre-operative measurement of cleft Mean of cleft width Mean of cleft height (Mm) (Mm) Group 1(n=35) 8,70± 2,68 11,31±1,71 Group 2(n=37) 9,93±2,87 11,31±1,81 P 0,064 0,988 (p>0,05, Chi-square test) 3.2 POST-OPERATIVE RESULTS Table 3.9: Results at 7th day Group Group Group Total p Results n % n % n % Good 28 93,3 25 83,3 53 88,3 0,228 Bad 6,7 16,7 11,7 35 100 37 100 72 100 Total (p>0,05, Chi-square test) Group 6,7% 17% 100% 50% bad 93,3% 83,3% good 0% group group Chart 3.5: Post-operative results at 7th day Table 3.10: Result of the graft after months Group Mean of height (mm) 9,88±1,76 Group (n=35) Group 8,59±2,21 (n=37) p 0,008 (p0,05, Chi-square test) Table 3.12: Ora-nasal fistula after months post-operation Group Group Total p Group n % n % n % Oro-nasal fistula Closed 100 100 100 0,468 Unclosed 00 00 00 5* 100 4* 100 100 Total (p>0,05, Chi-square test) Table 3.13: Post-operative result at months Mean Resorption rate Resorption rate Group Height (Compared with (Compared with baseline) months) Group 9,07±2,57 20,17±19,04 9,80±18,46 (n=35) Group 2 7,72±3,33 30,68±31,49 13,18±2,701 (n=37) 0,011* 0,001* 0,041* p (p0,05, Chi-square test) 16 Group Group (n=35) Group (n=37) p Table 3.15: Post-operative results after year Mean Height Resorption rate Resorption rate (Compared with (Compared with baseline) months) 7,60±2,15 32,67±17,84 15,35±10,95 6,52±3,39 41,86±29,61 21,22±29,71 0,039 0,043 0,042 (p0,05, Chi-square test) Table 3.17: Change in bone height at observation time (n=35) Bone height Median Min Max X ±SD Baseline months months 11,31±1,71 9,88±1,76 9,07±2,57 11,2 10,1 9,6 7,7 5,6 1,9 14,2 13,3 12,9 year 7,60±2,15 8,2 1,7 9,9 p03=0,0001 p06=0,0001 p36=0,001 p012=0,0001 p312=0,0001 p612=0,0001 (p 0.05) maybe the sample size is not big enough Although the surgery results in the first days are related to many factors, especially the skills of the surgeon But this study was conducted in a surgical department, the same group of surgeons, with a result of up to 10% difference showed the effectiveness of the presence of PRP in the graft material B Bone resorption According to Mooren in the second week, many inflammatory cells begin to appear, as well as moderate signs of bone resorption in the bone graft itself Accompanying it is the presence of osteoclasts By the 6th week after bone grafting: there was no sign of inflammation in the graft area Few signs of bone grafts have been identified The bone mass at this time is greatly reduced compared to the first week after bone transplant At 12 weeks post-graft: there is no sign of inflammation in the graft area Only a few signs of the graft bone are seen, but the boundary between the new bone and the new bone cannot be determined The slices through the graft not see empty spaces The bone resorption from week to week 12 is much less than the period from week to week At months after surgery in group 1, the bone height was measured 9.88 ± 1.76 compared to the baseline height 11.31 ± 1.71 with the rate of bone resorption recorded as 12.54 ± 9.45% In the second group, the bone height was measured at 8.59 ± 2.21so with the baseline height of 22 11.31 ± 1.81 with the bone resorption recorded as 23.68 ± 16.54% Thus, group is a group that only uses iliac bone grafting The bone reesorption is twice than that of group using iliac bone graft material + PRP + bone substitutes At months after surgery in group 1, the bone height measured 9.07 ± 2.57 compared with months after surgery, the bone resorption rate was recorded as 9.80 ± 18.46% In the second group, the bone height was 7.72 ± 3.33 compared with months after surgery, the rate of bone resorption was recorded as 13.18 ± 2.70% This result shows that the bone resorption was greatly reduced during this period The difference in bone resorption level between the two groups is not significant We think that this healing period only has the impact of artificial grafting materials, but they have also been regenerated in most of the graft, so the effect of osteoconduction and bone resorption is also significantly decreased And at the time of year after surgery in group 1, the bone height was measured 7.60 ± 2.15 compared to months after surgery, the bone resorption rate was recorded as 15.35 ± 10.95 % In the second group, the bone height was measured at 6.52 ± 3.39 compared to months after surgery The bone resorption rate was recorded at 21.22 ± 29.71% This period is stable with no regeneration activity in the grafting area, but the research results show that bone resorption is still happening, to a significant extentsion, but there is still a difference in bone resorption between the two research groups This difference is due to the composite material (artificial) due to its slow-digesting properties After year of grafting, the bone resorption rate, compared to the bone height in test group accounted for 32.67 ± 17.84% and group was 41.86 ± 29.61 Thus, the average bone height achieved in group is 68% (3/4 of the needed height) to achieve a type II bone grading according to Bergland's scale, while that of group is only 58% Finally, the differences in postoperative failure rates between the two study groups were significant The test group only had patients having secondary surgery, accounting for 6.6% While the control group had patients having a secondary surgery, accounting for 16.6% This is also clear evidence to show the effectiveness of PRP and bone substitute in combination with autologous bone for alveolar cleft graft 23 CONCLUSION Through this study, we have the following conclusions: Alveolar cleft morphology and related factors Alveolar cleft is a discontinuity of the maxillary dental arch Due to the continuous loss of the lip muscle, the impact of the tongue on the cleft area and the asymmetry of the muscles that adhere to the maxillary, along with the development of the patient's body, the anatomical form of the this defect is very various Not only the gap is wide or narrow, but also due to the healthy side often develops in the posteroanterior direction and rotates outward (in the same direction) And the alveolar on the cleft side develops towards the healthy side and posteriorly This causes the dental arches on both sides of the gap to be asymmetrical This anatomical deformation is highly dependent on the treatment planning from whether or not there was cleft lip or palate repair treatment, and whether or not orthodontic treatment was performed before grafting The discontinuity anatomical deformity of the dental arch effects the teeth in the gap, resulting in abnormal changes in the formation and eruption process, especially with the lateral incisors and canines Patients with alveolar cleft often have complications after cleft palate repair, such as oronasal fistula The recommended age for alveolar bone grafting is to 12 years old At this age the maxilla develops anteroposteriorly and so the bone grafting will not effect this growth, moreover grafting bone helps the maxilla continue to grow in vertical direction It also helps the teeth on the gap to erupt at the right time The alveolar cleft grafing in patients after lip and palate repair is a technique that contributes to the closure of the oronasal fistula with high success Alveolar cleft grafting help to reconstructmorphological structure of maxilla in the both volume and quality Not only does it create conditions for the teeth in the gap to erupt at the right time, but also create treatment steps for patients to continue orthodontic treatment, restorations for implant, prosthodontic and orthognathic surgery 24 Bone resorption after intervention with autologous bone and PRP, bone substitutes Alveolar grafting with autologous bone and PRP, bone substitutes is a safe procedure with little complications PRP extraction procedure can be performed at the same time with surgery It is also simple and safe with complication-free PRP with high concentration of platelet The growth factors released by platelet play important roles in anti-inflammation, stimulation of angiogenesis, so that it promotes the healing process They are also stimulating the bone cell differentiation and bone regeneration The bone substitutes help to make a scaffold for bone growth and to limit the bone resorption At the first months, the intervention show a significant reduction in bone resorption After months, the bone at the graft site has qualified for the next steps of treatment such as: orthodontics, prosthodontic, implant, or orthognathic surgery SUGGESTION 1.In the future, research on stem cell in alveolar cleft grafting should be conducted 2.Research on the impact of alveolar cleft grafting on the development of maxilla, as well as the total face should be carried out 3.Only a small proportion of alveolar cleft patients has been treated properly National announcement should be made so that patients and their family can have knowledge and proper treatment ... platelet-rich plasma, BMP, bioactive protein Bio-cells Mesenchymal cells, autologous bone In this study we chose the autologous bone graft material and the iliac crest and guided material These two materials