Polyphosphate (PolyP) for alveolar cleft repair, study protocol for a pilot randomized controlled trial.

2021 ◽  
Author(s):  
Salem Alkaabi ◽  
Diandra S Natsir Kalla ◽  
Abul Fauzi ◽  
Andi Tajrin ◽  
WEG Müller ◽  
...  
Keyword(s):  
Bone Formation ◽  
Cleft Lip ◽  
Controlled Trial ◽  
High Energy ◽  
Graft Material ◽  
Radiographic Imaging ◽  
Code Number ◽  
Alveolar Cleft ◽  
Cleft Lip Palate ◽  
Safety Parameters

Abstract Objective: Bone grafting is an important surgical procedure to restore missing bone in patients with alveolar cleft lip/palate, aiming to stabilize either sides of maxillary segments by inducing new bone formation, and in bilateral cleft cases also to stabilize the pre- maxilla. Polyphosphate (PolyP), a physiological polymer composed of orthophosphate units linked together with high-energy phosphate bonds, is a naturally existing compound in platelets which, when complexed with calcium as Ca-polyP microparticles (Ca-polyP MPs), was proven to have osteoinductive properties in preclinical studies. Aim: To evaluate the feasibility, safety and osteoinductivity of Ca-polyP MPs as a bone-inducing graft material in humans. Methods: This prospective non-blinded first-in-man clinical pilot study shall consist of 8 alveolar cleft patients of 13 years or older to evaluate the feasibility and safety of Ca-PolyP MPs as a bone-inducing graft material. Patients will receive Ca-polyP graft material only, or Ca-polyP in combination with biphasic calcium phosphate (BCP) as a bone substitute carrier. During the trial, the participants will be investigated closely for safety parameters using radiographic imaging, regular blood tests, and physical examinations. After 6 months, a hollow drill will be used to prepare the implantation site to obtain a biopsy. The radiographic imaging will be used for clinical evaluation; the biopsy will be processed for histological/histomorphometric evaluation of bone formation. Discussion: This is the first-in-man study evaluating the safety and feasibilty of the polyP as well as the potential regenerative capacity of polyP using an alveolar cleft model.Trial registration {31a} The clinical trial protocol received a written approval by the ethical committee of Faculty of Medicine, Hasanuddin University, Makassar, Indonesia with code number 1063/UN4.6.4.5.31/PP36/2019. On completion of the trial, the results on safety, feasibility and bone formation with polyP as graft material will published.

scholarly journals Polyphosphate (PolyP) for alveolar cleft repair: study protocol for a pilot randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
S. A. Alkaabi ◽  
D. S. Natsir Kalla ◽  
G. A. Alsabri ◽  
A. Fauzi ◽  
A. Tajrin ◽  
...  
Keyword(s):  
Bone Formation ◽  
Cleft Lip ◽  
Controlled Trial ◽  
High Energy ◽  
Graft Material ◽  
Radiographic Imaging ◽  
Alveolar Cleft ◽  
Cleft Lip Palate ◽  
Safety Parameters ◽  
Physical Examinations

Abstract Objective Bone grafting is an important surgical procedure to restore missing bone in patients with alveolar cleft lip/palate, aiming to stabilize either sides of the maxillary segments by inducing new bone formation, and in bilateral cleft cases also to stabilize the pre-maxilla. Polyphosphate (PolyP), a physiological polymer composed of orthophosphate units linked together with high-energy phosphate bonds, is a naturally existing compound in platelets which, when complexed with calcium as Ca-polyP microparticles (Ca-polyP MPs), was proven to have osteoinductive properties in preclinical studies. Aim To evaluate the feasibility, safety, and osteoinductivity of Ca-polyP MPs as a bone-inducing graft material in humans. Methods This prospective non-blinded first-in-man clinical pilot study shall consist of 8 alveolar cleft patients of 13 years or older to evaluate the feasibility and safety of Ca-PolyP MPs as a bone-inducing graft material. Patients will receive Ca-polyP graft material only or Ca-polyP in combination with biphasic calcium phosphate (BCP) as a bone substitute carrier. During the trial, the participants will be investigated closely for safety parameters using radiographic imaging, regular blood tests, and physical examinations. After 6 months, a hollow drill will be used to prepare the implantation site to obtain a biopsy. The radiographic imaging will be used for clinical evaluation; the biopsy will be processed for histological/histomorphometric evaluation of bone formation. Discussion This is the first-in-man study evaluating the safety and feasibility of the polyP as well as the potential regenerative capacity of polyP using an alveolar cleft model. Trial registration Indonesian Trial Registry INA-EW74C1N. Registered on 12 June 2020

scholarly journals Safety and feasibility study of using Polyphosphate (PolyP) in alveolar cleft repair, A Pilot study.

2021 ◽  
Author(s):  
Salem Alkaabi ◽  
Natsir Kalla ◽  
Alsabri GA ◽  
A Fauzi ◽  
Jansen NA ◽  
...  
Keyword(s):  
Pilot Study ◽  
Calcium Phosphate ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Alveolar Bone ◽  
High Energy ◽  
Close Monitoring ◽  
Code Number ◽  
Alveolar Cleft ◽  
Safety Parameters

Abstract Background: Bone grafting is an important surgical procedure to reconstruct alveolar bone defects in patients with cleft lip and palate. Polyphosphate (PolyP) is a physiological polymer present in blood, primarily in platelets. PolyP is playing a role as phosphate source in bone calcium phosphate deposition. Moreover, the cleavage of high-energy bonds to release phosphates provides local energy necessary for regenerative processes. In this study, polyP is complexed with calcium to form Calcium polyP microparticles (Ca-polyP MPs), which were shown to have osteoinductive properties in preclinical studies. The aim of this study was to evaluate the feasibility, safety and osteoinductivity of Ca-polyP MPs in-first human clinical trial.Methods: This single blinded, randomized, prospective clinical pilot study enrolled eight adolescent patients (mean age 18.1: range 13 - 34 years) with residual alveolar bone cleft. Randomization in two groups (four receiving Ca-polyP MPs only, four a combination of Ca-polyP MPs and biphasic calcium phosphate (BCP)) was performed. Patient follow-up was six months. Outcome parameters included safety parameters and close monitoring of possible adverse effects using radiographic imaging, regular blood tests, and physical examinations.Results: Due to surgical and technical reasons, eventually only 2 patients received Ca-polyP MPs, and the others the combination graft. All patients were assessed up to day 90. Four out of eight were able to continue with the final assessment day (day180). Three out eight were unable to reach the hospital due to Covid-19 restrictions. One patient decided not to continue with the study.No allergies or remarkable local or systematic reaction were noticed in all patients. Radiographically, patients receiving Ca-polyP MPs only were scored grade IV Bergland scale, while patients received combination Ca-polyP MPs and BCP were ranged from score I to III.Conclusions: Ca-polyP MPs and combination of Ca-polyP MPs/BCP are safe graft materials, however, Ca-polyP MPs alone are not sufficiently stable defect-filling scaffolds to be used in alveolar cleft repair.Trial registration: Indonesian Trial Registry under number INA-EW74C1N by the ethical committee of Faculty of Medicine, Hasanuddin University, Makassar, Indonesia with code number 1063/UN4.6.4.5.31/PP36/2019

scholarly journals Safety and feasibility study of using polyphosphate (PolyP) in alveolar cleft repair: a pilot study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Salem A. Alkaabi ◽  
Diandra Sabrina Natsir Kalla ◽  
Ghamdan A. Alsabri ◽  
Abul Fauzi ◽  
Nova Jansen ◽  
...  
Keyword(s):  
Pilot Study ◽  
Calcium Phosphate ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Alveolar Bone ◽  
High Energy ◽  
Close Monitoring ◽  
Code Number ◽  
Alveolar Cleft ◽  
Safety Parameters

Abstract Background Bone grafting is an important surgical procedure to reconstruct alveolar bone defects in patients with cleft lip and palate. Polyphosphate (PolyP) is a physiological polymer present in the blood, primarily in platelets. PolyP plays a role as a phosphate source in bone calcium phosphate deposition. Moreover, the cleavage of high-energy bonds to release phosphates provides local energy necessary for regenerative processes. In this study, polyP is complexed with calcium to form Calcium polyP microparticles (Ca-polyP MPs), which were shown to have osteoinductive properties in preclinical studies. The aim of this study was to evaluate the feasibility, safety, and osteoinductivity of Ca-polyP MPs, alone or in combination with BCP, in a first-in-human clinical trial. Methods This single-blinded, parallel, prospective clinical pilot study enrolled eight adolescent patients (mean age 18.1: range 13–34 years) with residual alveolar bone cleft. Randomization in two groups (four receiving Ca-polyP MPs only, four a combination of Ca-polyP MPs and biphasic calcium phosphate (BCP)) was performed. Patient follow-up was 6 months. Outcome parameters included safety parameters and close monitoring of possible adverse effects using radiographic imaging, regular blood tests, and physical examinations. Osteoinductivity evaluation using histomorphometric analysis of biopsies was not possible due to COVID restrictions. Results Due to surgical and feasibility reasons, eventually, only 2 patients received Ca-polyP MPs, and the others the combination graft. All patients were assessed up to day 90. Four out of eight were able to continue with the final assessment day (day 180). Three out of eight were unable to reach the hospital due to COVID-19 restrictions. One patient decided not to continue with the study. None of the patients showed any allergic reactions or any remarkable local or systematic side effects. Radiographically, patients receiving Ca-polyP MPs only were scored grade IV Bergland scale, while patients who got the BCP/Ca-polyP MPs combination had scores ranging from I to III. Conclusions Our results indicate that Ca-polyP MPs and the BCP/Ca-polyP MPs combination appear to be safe graft materials; however, in the current setting, Ca-polyP MPs alone may not be a sufficiently stable defect-filling scaffold to be used in alveolar cleft repair. Trial registration Indonesian Trial Registry under number INA-EW74C1N by the ethical committee of Faculty of Medicine, Hasanuddin University, Makassar, Indonesia with code number 1063/UN4.6.4.5.31/PP36/2019.

scholarly journals Alveolar cleft and maximum cleft width as predictors for difficult laryngoscopy and intubation in patients with unilateral complete cleft lip and palate

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Gamal A. Abdelhameed ◽  
Wael A. Ghanem ◽  
Simon H. Armanios ◽  
Tamer Nabil Abdelrahman
Keyword(s):  
Body Weight ◽  
Odds Ratio ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Difficult Laryngoscopy ◽  
Secondary Outcome ◽  
Pediatric Airway ◽  
Alveolar Cleft ◽  
Cleft Lip Palate ◽  
Width Measurements

Abstract Background Cleft lip and palate is one of the commonest congenital anomalies, which have an impact on feeding, speech, and dental development away from the significant psychosocial sequel. Early surgical repair aims to restore appearance and function, and the modern techniques can leave many defects undetectable. Therefore, the anesthetic challenge facing the pediatric airway with such abnormalities is still of a great impact. The aim of our study among 189 patients enrolled is to correlate alveolar gap and maximum cleft width measurements as predictors of difficult laryngoscopy and intubation in infants with unilateral complete cleft lip/palate aging from 1 to 6 months. As a secondary outcome, their weight is to be correlated too as another parameter. Results The alveolar gap and maximum cleft width are both of equal high predictive power (p value ≤ 0.001) with 100% sensitivity for both and specificity of 76.10% and 82.39% respectively, with a cut off value of ≤ 10 mm and 11 mm for these dimensions respectively, and odds ratio of incidence of difficult intubation is 4.18 and 5.68 respectively, while body weight ≤ 5.75 kg has an odds ratio of 2.32. Conclusion Alveolar cleft and maximum cleft width can be used as predictors for anticipation of difficult laryngoscopy and intubation infant patients with unilateral complete cleft lip and palate, while body weight ≤ 5.75 kg increases the risk more than twice.

scholarly journals Regeneration in Experimental Alveolar Bone Defect Using Human Umbilical Cord Mesenchymal Stem Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972097539
Author(s):  
Akiko Toyota ◽  
Rei Shinagawa ◽  
Mikiko Mano ◽  
Kazuyuki Tokioka ◽  
Naoto Suda
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Cleft Lip ◽  
Human Umbilical Cord ◽  
Bone Surface ◽  
Bone Bridge ◽  
Bridge Formation ◽  
Alveolar Cleft ◽  
Umbilical Cords

Cleft lip and palate is a congenital disorder including cleft lip, and/or cleft palate, and/or alveolar cleft, with high incidence.The alveolar cleft causes morphological and functional abnormalities. To obtain bone bridge formation and continuous structure between alveolar clefts, surgical interventions are performed from infancy to childhood. However, desirable bone bridge formation is not obtained in many cases. Regenerative medicine using mesenchymal stem cells (MSCs) is expected to be a useful strategy to obtain sufficient bone bridge formation between alveolar clefts. In this study, we examined the effect of human umbilical cord-derived MSCs by transplantation into a rat experimental alveolar cleft model. Human umbilical cords were digested enzymatically and the isolated cells were collected (UC-EZ cells). Next, CD146-positive cells were enriched from UC-EZ cells by magnetic-activated cell sorting (UC-MACS cells). UC-EZ and UC-MACS cells showed MSC gene/protein expression, in vitro. Both cells had multipotency and could differentiate to osteogenic, chondrogenic, and adipogenic lineages under the differentiation-inducing media. However, UC-EZ cells lacked Sox2 expression and showed the lower ratio of MSCs than UC-MACS cells. Thus, UC-MACS cells were transplanted with hydroxyapatite and collagen (HA + Col) into alveolar cleft model to evaluate bone formation in vivo. The results of micro computed tomography and histological staining showed that UC-MACS cells with HA + Col induced more abundant bone formation between the experimental alveolar clefts than HA + Col implantation only. Cells immunopositive for osteopontin were accumulated along the bone surface and some of them were embedded in the bone. Cells immunopositive for human-specific mitochondria were aligned along the newly formed bone surface and in the new bone, suggesting that UC-MACS cells contributed to the bone bridge formation between alveolar clefts. These findings indicate that human umbilical cords are reliable bioresource and UC-MACS cells are useful for the alveolar cleft regeneration.

Simultaneous Harvesting of Cancellous Iliac Bone for Alveolar Cleft Closure and Dermis for Augmentation of Median Tubercle

2009 ◽  
Vol 46 (3) ◽  
pp. 295-298 ◽  
Author(s):  
Derek M. Steinbacher ◽  
Bonnie L. Padwa ◽  
John B. Mulliken
Keyword(s):  
Cancellous Bone ◽  
Cleft Lip ◽  
Posterior Approach ◽  
Donor Site ◽  
Iliac Region ◽  
Dermal Graft ◽  
Alveolar Cleft ◽  
Cleft Lip Palate ◽  
Cleft Closure ◽  
Secondary Closure

Children with repaired cleft lip/palate require secondary closure of the alveolar cleft and, often, nasolabial revision. We describe a technique performed in 61 patients for harvesting bone for the alveolar defect and dermis for augmentation of the median tubercle, taking both from the posterior iliac region. The advantages of the posterior approach are as follows: (1) the same donor site is used for cancellous bone and dermal graft and (2) the child's appearance is improved along with alveolar cleft grafting.

scholarly journals Demineralized Bone Matrix for Alveolar Cleft Management

2014 ◽  
Vol 7 (4) ◽  
pp. 251-257 ◽  
Author(s):  
Jose Rolando Prada Madrid ◽  
Viviana Gomez ◽  
Bibiana Mendoza
Keyword(s):  
Bone Formation ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Demineralized Bone Matrix ◽  
Bone Matrix ◽  
Case Series ◽  
Alveolar Cleft ◽  
Case Series Study ◽  
Demineralized Bone

The aim of this article is to describe the results of the use of demineralized bone matrix putty in alveolar cleft of patients with cleft lip and palate. We performed a prospective, descriptive case series study, in which we evaluated the results of the management of alveolar clefts with demineralized bone matrix. Surgery was performed in 10 patients aged between 7 and 26 years (mean 13 years), involving a total of 13 clefts in the 10 patients. A preoperative cone beam computed tomography (CBCT) was taken to the patients in whom the width of the cleft was measured from each edge of the cleft reporting values between 5.76 and 16.93 mm (average, 11.18 mm). The densities of the clefts were measured with a CBCT, 6 months postoperative to assess bone formation. The results showed a register of gray values of 1,148 to 1,396 (mean, 1,270). The follow-up was conducted for 15 to 33 months (mean, 28.2 months). The results did not show satisfactory bone formation in the cleft of patients with the use of demineralized bone matrix.

scholarly journals Closure of Oronasal Fistulae Post Palatoraphy with Tongue Flap in Bilateral Complete Cleft Lip Palate Patient: A Case Report

2021 ◽  
Vol 16 (Supp. 1) ◽  
pp. 59-65
Author(s):  
Menik Sayekti ◽  
Liska Barus ◽  
Ni Putu Mira Sumarta ◽  
Norifumi Nakamura
Keyword(s):  
Cleft Lip ◽  
Surrounding Tissue ◽  
Common Complication ◽  
Closure Technique ◽  
Alveolar Cleft ◽  
Tongue Flap ◽  
Fibrotic Tissue ◽  
Cleft Lip Palate ◽  
Palate Patient ◽  
Tissue Defects

Oronasal fistulae are common complication following palatoraphy. There are several surgical procedures to repair oronasal fistulae. However, conventional oronasal fistulae closure technique is not always possible, especially when the surrounding tissue is replaced by fibrotic tissue due to previous palatoraphy. Tissue defects in oronasal fistulae should be replaced with tissues providing good vascularisation such as pedicle tongue flap. A case of pedicle tongue flap used to close oronasal fistulae was reported. Eleven-year-old girl, presented with oronasal fistulae and bilateral alveolar cleft after previous palatoraphy. The oronasal fistulae were closed with pedicled tongue flap. The healing was uneventful, and the division of the pedicle tongue flap was done three weeks later and closed primarily. There was no dehiscence of the wound and masticatory functions were recorded. Vascularised flap such as pedicle tongue flap is a preferred technique to close oronasal fistulae after palatoraphy.

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