Effect of Bone Marrow Mononuclear Cell Layer Seeded on Platelet-rich Fibrin on an Alveolar Socket After Extraction

NCT ID: NCT05465421

Last Updated: 2022-07-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-01

Study Completion Date

2023-05-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Bone marrow aspiration from maxillary tuberosity will be centrifuged to separate the bone marrow mononuclear cell layer using the density gradient separation method, then it will be seeded in a platelet-rich fibrin membrane and used for socket preservation to test the osteogenic ability of the bone marrow mononuclear cell layer in comparison to platelet-rich fibrin alone both ways will receive implant after 3 months

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

-Research question: In patients with teeth requiring extraction will bone marrow mononuclear cell layer (BMMNC) from maxillary tuberosity seeded on platelet-rich fibrin (PRF) maintain the bucco-palatal/lingual bone dimension during socket preservation compared to platelet rich fibrin alone?

-The rationale for conducting the research: Bone marrow is full of progenitors and cell markers that promote tissue healing. Traditionally bone marrow aspiration is done from extra-oral sites. The obstacle in extra-oral aspiration is the site morbidity and the need to put the patient under general anesthesia.

Intraoral sites like the maxillary tuberosity are filled with marrow spaces that can facilitate the harvesting of marrow cells and reduce the trauma of the harvesting process.

Bone marrow mononuclear cell (BMMNC) transplantation may result in higher rates of bone marrow regeneration in the extraction socket and significantly accelerate bone maturation. It is also suggested that Bone marrow mononuclear cell (BMMNC) plays an important role in bone homeostasis within the extraction socket However, Bone marrow mononuclear cell (BMMNC) has several drawbacks that should be taken into consideration like potential pain during harvest, and variable stem cell quantity and quality depending on age which may hinder the usage of Bone marrow mononuclear cell (BMMNC) in old ages.

The bone regeneration ability of that population of cells and the ease of their acquisition render them good candidates for socket preservation. Hence, the current study aims to evaluate the use of Bone marrow mononuclear cells (BMMNC) obtained from the maxillary tuberosity in promoting bone formation in the alveolar socket after extraction.

-The explanation for the choice of comparators: A parallel group of 12 patients with a non-restorable tooth will undergo extraction and socket preservation.

* In group 1: socket preservation will be done by PRF PRF membrane used in the extraction sockets was demonstrated to promote local soft tissue healing of gums and reduce postoperative pain response. While the effect of PRF to reduce alveolar bone resorption was not significant, PRF was able to increase the quality of the novel bone and enhance the rate of bone formation due to the concentration of growth factors
* In group 2: sock preservation will be done by Bone marrow mononuclear cell (BMMNC) from the maxillary tuberosity on PRF

In the current study, the density gradient separation method technique will be used to harvest BMMNC. This method has been used to enrich the isolated mononuclear cell fraction and has been an essential part of several clinical procedures. The density gradient separation/immediate transplantation method is superior to the in vitro expansion method as the cells are minimally manipulated; there is no invasive enzymatic treatment used. This method allows immediate autologous transplantation of BMAC that minimizes the risk of contamination by decreasing the time of cell handling in cell culture

-Objectives: The objective of the study is to find out the osteogenic potential of BMMNC from the maxillary tuberosity in comparison with PRF alone in socket preservation for delayed implant placement

-Trial design:

The current study will be designed as a:

* Parallel 2 arm
* Randomized Controlled Clinical Trial,
* Allocation ratio 1:1
* Superiority Trial

* Methods

. Interventions
* Preoperative evaluation:
* Clinical examination \& informed consent:

Evaluation of the patient's general condition of the oral cavity, to make sure it complies with the criteria required to be enrolled in the study in terms of oral hygiene, pathological conditions

-Radiographic examination:

Cone beam CT will be taken before proceeding with any procedure to make sure of the restorability of the tooth before extraction, checking for any radiolucency to be removed also to measure bone width before extraction

* Surgical procedures:
* Local anesthesia will be administered by infiltration or nerve block to achieve the necessary anesthesia to allow extraction of the indicated tooth
* Extraction will be done as atraumatically as possible removing any pathosis found that may interfere with bone formation
* Allocation concealment will be broken and socket preservation will be done In group 1
* A trapezoidal flap will be created above the extraction socket to allow closure of the surgical site.
* PRF will be placed in the socket
* The flap will be closed by interrupted sutures using 5-0 sutures. In group 2 (test group)
* A trapezoidal flap will be created above the extraction socket to allow closure of the surgical site.
* BMMNC will be seeded on platelet-rich fibrin and inserted into the socket
* The flap will be closed by interrupted sutures using 5-0 sutures.

BMMNCs aspiration and centrifugation technique:

* Under the supervision of professor: Hani el Nahass and doctor: Omnia k Tawfik A 20 gauge needle will be inserted in the maxillary tuberosity area through the palatal aspect until aspiration is positive
* Aspirate will be collected in a heparin-treated tube (2000:1) using 1ml of anticoagulant citrate dextrose solution (ACD-A) for every 15ml of bone marrow aspiration.
* Aspirate will be centrifuged to separate the BMMNCs using the density gradient separation method.
* Ficoll® Paque Plus (GE Healthcare, Buckinghamshire, UK) bottle will be inverted several times to ensure thorough mixing and 3 ml of the media will be added to a centrifuge tube
* The bone marrow aspirate will be diluted (1:1) with saline and then carefully layered onto the Ficoll gradient and then centrifuged at 2000 rpm for 20 min at room temperature using a multi-speed 4000 rpm vertical rotor.
* The upper layer containing plasma and platelets will be collected using a sterile pipette, leaving the mononuclear cell layer undisturbed at the interface. The layer of mononuclear cells will be transferred to a sterile centrifuge tube using a sterile pipette.
* Postsurgical procedure (three months after socket preservation)
* Local anesthesia will be administered by infiltration or nerve block to achieve the necessary anesthesia
* A flap will be raised at the site of the extracted tooth
* A core biopsy will be harvested by introducing a core drill bit in place of an initial drill
* Sequential drilling will take place to prepare osteotomy to the right size to receive an implant
* Implant will be placed in the osteotomy with the platform flush with the bone
* Flap closure will be achieved by interrupted 5-0 sutures

Histologic processing:

The harvested bone biopsies will be decalcified in ethylene diamine tetra acetic acid (10%) for two weeks. After dehydration in graded series of ethanol, the specimens will be embedded in paraffin and sectioned by a high-speed rotating blade microtome; the sections will be stained with hematoxylin-eosin stain. This will be followed by histomorphometric analysis using the Leica Qwin 500 (Leica microsystems Inc., Switzerland) image analyzer computer system (England). Area percentage (%) of newly formed bone will be calculated

Quantitative real-time polymerase chain reaction (qRT-PCR)

real-time polymerase chain reaction(RT-PCR) will be used to analyze the massenger Ribonucleic acid (mRNA) levels of alkaline phosphatase

• Postoperative instructions and follow-up:

Administration of:

* Antibiotics (Amoxicillin 1g twice daily for 5 days) to prevent any chance of infection. (Eugenio Romeo et al, 2014).
* Anti-inflammatory drugs (NSAIDS; Ibuprofen 600mg three times daily for 5 days) to avoid any chance of edema or pain or swelling
* Antiseptic mouth rinse (0.12% Chlorhexidine oral rinse will be prescribed for 60 seconds two times a day for 14 days.
* The patient will be instructed to follow up for the next 3 months before implant placement

Patient self-care instructions:

* Application of an ice bag to the treated area for the first 24 hours.
* Avoid any brushing and trauma to the surgical site for one week.
* Avoid smoking

* Outcomes:

PICO:(population-intervention-compatetor-outcome) P: Patients with non-restorable teeth indicated for extraction I: BMMNC from the tuberosity for socket preservation C: Platelet rich fibrin O: Bucco-palatal/lingual bone dimension Prioritization of Outcome Outcome Method of Measurement Unit of Measurement Primary outcome

Secondary objectives To calculate the postoperative pain, patient satisfaction and Alkaline phosphatase measurement in a histological sample of the newly formed bone took 3 months later before implant placement

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Decayed Teeth

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors
Blinding of the participants and the operator is is not applicable, however outcome assessors and biostatistician will be blinded.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

socket preservation with platelet rich fibrin PRF alone the implant placement 3 months after

after extraction socket preservation will be done by using PRF only in the socket and closed the socket by flap advancement.

Group Type ACTIVE_COMPARATOR

bone marrow aspiration from maxillary tuberosity and BMMNCs separation to be seeded on PRF and used for socket preservation

Intervention Type OTHER

Local anaesthesia will be administered by infiltration or nerve block to achieve the necessary anaesthesia to allow extraction of the indicated tooth Extraction will be done as atraumatically as possible removing any pathosis found that may interfere with bone formation A trapezoidal flap will be created above the extraction socket to allow closure of the surgical site.

BMMNC will be seeded on platelet rich fibrin and inserted in the socket The flap will be closed by interrupted sutures using 5-0 sutures. implant placement 3 months later

socket preservation with BMMNCs of bone marrow aspirated of maxillary tuberosity

after extraction socket preservation will be done by using bone marrow mononuclear cell layer seeded on PRF in the socket and close the socket by flap advancement

Group Type EXPERIMENTAL

bone marrow aspiration from maxillary tuberosity and BMMNCs separation to be seeded on PRF and used for socket preservation

Intervention Type OTHER

Local anaesthesia will be administered by infiltration or nerve block to achieve the necessary anaesthesia to allow extraction of the indicated tooth Extraction will be done as atraumatically as possible removing any pathosis found that may interfere with bone formation A trapezoidal flap will be created above the extraction socket to allow closure of the surgical site.

BMMNC will be seeded on platelet rich fibrin and inserted in the socket The flap will be closed by interrupted sutures using 5-0 sutures. implant placement 3 months later

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

bone marrow aspiration from maxillary tuberosity and BMMNCs separation to be seeded on PRF and used for socket preservation

Local anaesthesia will be administered by infiltration or nerve block to achieve the necessary anaesthesia to allow extraction of the indicated tooth Extraction will be done as atraumatically as possible removing any pathosis found that may interfere with bone formation A trapezoidal flap will be created above the extraction socket to allow closure of the surgical site.

BMMNC will be seeded on platelet rich fibrin and inserted in the socket The flap will be closed by interrupted sutures using 5-0 sutures. implant placement 3 months later

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patients with badly decayed tooth indicated for extraction
* Patients with healthy systemic condition (Medically free)
* Adequate inter-arch space for placement of the implant prosthetic part.
* Good oral hygiene
* Cooperative patients who are willing to commit for 6 months follow up

Exclusion Criteria

* Smokers
* Pregnant females
* Patient with medical condition that contraindicates surgical procedures
* Patients on medication that may interfere with healing (corticosteroids, bisphosphonate, Chemo/radio therapy).
* Patients with habits that may jeopardize the implant longevity and affect the results of the study such as alcoholism or parafunctional habits.
Minimum Eligible Age

22 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Cairo University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Hani Elnahass

clinical professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Hani ElNahass

Role: STUDY_DIRECTOR

Cairo University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Cairo University

Cairo, , Egypt

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Egypt

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Ahmed I Yassin

Role: CONTACT

002 01063718668

omnia K Tawfik, lectuerer

Role: CONTACT

002 01118881217

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Role: primary

02 35676105

References

Explore related publications, articles, or registry entries linked to this study.

Sauerbier S, Rickert D, Gutwald R, Nagursky H, Oshima T, Xavier SP, Christmann J, Kurz P, Menne D, Vissink A, Raghoebar G, Schmelzeisen R, Wagner W, Koch FP. Bone marrow concentrate and bovine bone mineral for sinus floor augmentation: a controlled, randomized, single-blinded clinical and histological trial--per-protocol analysis. Tissue Eng Part A. 2011 Sep;17(17-18):2187-97. doi: 10.1089/ten.TEA.2010.0516. Epub 2011 Jun 24.

Reference Type BACKGROUND
PMID: 21529247 (View on PubMed)

Pasquali PJ, Teixeira ML, de Oliveira TA, de Macedo LG, Aloise AC, Pelegrine AA. Maxillary Sinus Augmentation Combining Bio-Oss with the Bone Marrow Aspirate Concentrate: A Histomorphometric Study in Humans. Int J Biomater. 2015;2015:121286. doi: 10.1155/2015/121286. Epub 2015 Oct 12.

Reference Type BACKGROUND
PMID: 26543482 (View on PubMed)

Wildburger A, Payer M, Jakse N, Strunk D, Etchard-Liechtenstein N, Sauerbier S. Impact of autogenous concentrated bone marrow aspirate on bone regeneration after sinus floor augmentation with a bovine bone substitute--a split-mouth pilot study. Clin Oral Implants Res. 2014 Oct;25(10):1175-81. doi: 10.1111/clr.12228. Epub 2013 Jul 22.

Reference Type BACKGROUND
PMID: 23875876 (View on PubMed)

Sauerbier S, Stricker A, Kuschnierz J, Buhler F, Oshima T, Xavier SP, Schmelzeisen R, Gutwald R. In vivo comparison of hard tissue regeneration with human mesenchymal stem cells processed with either the FICOLL method or the BMAC method. Tissue Eng Part C Methods. 2010 Apr;16(2):215-23. doi: 10.1089/ten.TEC.2009.0269.

Reference Type BACKGROUND
PMID: 19473102 (View on PubMed)

Muschler GF, Boehm C, Easley K. Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume. J Bone Joint Surg Am. 1997 Nov;79(11):1699-709. doi: 10.2106/00004623-199711000-00012.

Reference Type BACKGROUND
PMID: 9384430 (View on PubMed)

Sununliganon L, Peng L, Singhatanadgit W, Cheung LK. Osteogenic efficacy of bone marrow concentrate in rabbit maxillary sinus grafting. J Craniomaxillofac Surg. 2014 Dec;42(8):1753-65. doi: 10.1016/j.jcms.2014.06.011. Epub 2014 Jun 14.

Reference Type BACKGROUND
PMID: 25052732 (View on PubMed)

Duttenhoefer F, Hieber SF, Stricker A, Schmelzeisen R, Gutwald R, Sauerbier S. Follow-up of implant survival comparing ficoll and bone marrow aspirate concentrate methods for hard tissue regeneration with mesenchymal stem cells in humans. Biores Open Access. 2014 Apr 1;3(2):75-6. doi: 10.1089/biores.2014.0003.

Reference Type BACKGROUND
PMID: 24804168 (View on PubMed)

de Oliveira TA, Aloise AC, Orosz JE, de Mello E Oliveira R, de Carvalho P, Pelegrine AA. Double Centrifugation Versus Single Centrifugation of Bone Marrow Aspirate Concentrate in Sinus Floor Elevation: A Pilot Study. Int J Oral Maxillofac Implants. 2016 Jan-Feb;31(1):216-22. doi: 10.11607/jomi.4170.

Reference Type BACKGROUND
PMID: 26800181 (View on PubMed)

Gapski R, Satheesh K, Cobb CM. Histomorphometric analysis of bone density in the maxillary tuberosity of cadavers: a pilot study. J Periodontol. 2006 Jun;77(6):1085-90. doi: 10.1902/jop.2006.050118.

Reference Type BACKGROUND
PMID: 16734586 (View on PubMed)

Al-Ahmady HH, Abd Elazeem AF, Bellah Ahmed NE, Shawkat WM, Elmasry M, Abdelrahman MA, Abderazik MA. Combining autologous bone marrow mononuclear cells seeded on collagen sponge with Nano Hydroxyapatite, and platelet-rich fibrin: Reporting a novel strategy for alveolar cleft bone regeneration. J Craniomaxillofac Surg. 2018 Sep;46(9):1593-1600. doi: 10.1016/j.jcms.2018.05.049. Epub 2018 Jun 2.

Reference Type BACKGROUND
PMID: 30196860 (View on PubMed)

Araujo MG, Lindhe J. Dimensional ridge alterations following tooth extraction. An experimental study in the dog. J Clin Periodontol. 2005 Feb;32(2):212-8. doi: 10.1111/j.1600-051X.2005.00642.x.

Reference Type BACKGROUND
PMID: 15691354 (View on PubMed)

Zhang Y, Ruan Z, Shen M, Tan L, Huang W, Wang L, Huang Y. Clinical effect of platelet-rich fibrin on the preservation of the alveolar ridge following tooth extraction. Exp Ther Med. 2018 Mar;15(3):2277-2286. doi: 10.3892/etm.2018.5696. Epub 2018 Jan 4.

Reference Type BACKGROUND
PMID: 29456635 (View on PubMed)

Mashimo T, Sato Y, Akita D, Toriumi T, Namaki S, Matsuzaki Y, Yonehara Y, Honda M. Bone marrow-derived mesenchymal stem cells enhance bone marrow regeneration in dental extraction sockets. J Oral Sci. 2019;61(2):284-293. doi: 10.2334/josnusd.18-0143.

Reference Type BACKGROUND
PMID: 31217377 (View on PubMed)

Marx RE, Tursun R. A qualitative and quantitative analysis of autologous human multipotent adult stem cells derived from three anatomic areas by marrow aspiration: tibia, anterior ilium, and posterior ilium. Int J Oral Maxillofac Implants. 2013 Sep-Oct;28(5):e290-4. doi: 10.11607/jomi.te10.

Reference Type BACKGROUND
PMID: 24066346 (View on PubMed)

Iorio-Siciliano V, Blasi A, Nicolo M, Iorio-Siciliano A, Riccitiello F, Ramaglia L. Clinical Outcomes of Socket Preservation Using Bovine-Derived Xenograft Collagen and Collagen Membrane Post-Tooth Extraction: A 6-Month Randomized Controlled Clinical Trial. Int J Periodontics Restorative Dent. 2017 Sep/Oct;37(5):e290-e296. doi: 10.11607/prd.2474.

Reference Type BACKGROUND
PMID: 28817143 (View on PubMed)

Barone A, Aldini NN, Fini M, Giardino R, Calvo Guirado JL, Covani U. Xenograft versus extraction alone for ridge preservation after tooth removal: a clinical and histomorphometric study. J Periodontol. 2008 Aug;79(8):1370-7. doi: 10.1902/jop.2008.070628.

Reference Type BACKGROUND
PMID: 18672985 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

https://pubmed.ncbi.nlm.nih.gov/21529247/

Bone marrow concentrate and bovine bone mineral for sinus floor augmentation

https://pubmed.ncbi.nlm.nih.gov/26543482/

Maxillary Sinus Augmentation Combining Bio-Oss with the Bone Marrow Aspirate Concentrate

https://pubmed.ncbi.nlm.nih.gov/23875876/

Impact of autogenous concentrated bone marrow aspirate on bone regeneration after sinus floor augmentation with a bovine bone substitute

http://pubmed.ncbi.nlm.nih.gov/19473102/

In vivo comparison of hard tissue regeneration with human mesenchymal stem cells processed with either the FICOLL method or the BMAC method

http://pubmed.ncbi.nlm.nih.gov/9384430/

Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume

http://pubmed.ncbi.nlm.nih.gov/25052732/

Osteogenic efficacy of bone marrow concentrate in rabbit maxillary sinus grafting

http://pubmed.ncbi.nlm.nih.gov/24804168/

Follow-up of implant survival comparing ficoll and bone marrow aspirate concentrate methods for hard tissue regeneration with mesenchymal stem cells in humans

https://pubmed.ncbi.nlm.nih.gov/26800181/

Double Centrifugation Versus Single Centrifugation of Bone Marrow Aspirate Concentrate in Sinus Floor Elevation: A Pilot Study

https://pubmed.ncbi.nlm.nih.gov/30196860/

Combining autologous bone marrow mononuclear cells seeded on collagen sponge with Nano Hydroxyapatite, and platelet-rich fibrin

https://pubmed.ncbi.nlm.nih.gov/15691354/

Dimensional ridge alterations following tooth extraction

https://pubmed.ncbi.nlm.nih.gov/29456635/

Clinical effect of platelet-rich fibrin on the preservation of the alveolar ridge following tooth extraction

https://keio.pure.elsevier.com/en/publications/bone-marrow-derived-mesenchymal-stem-cells-enhance-bone-marrow-re

Bone marrow-derived mesenchymal stem cells enhance bone marrow regeneration in dental extraction sockets

https://pubmed.ncbi.nlm.nih.gov/24066346/

A qualitative and quantitative analysis of autologous human multipotent adult stem cells derived from three anatomic areas by marrow aspiration: tibia, anterior ilium, and posterior ilium

https://pubmed.ncbi.nlm.nih.gov/28817143/

Clinical Outcomes of Socket Preservation Using Bovine-Derived Xenograft Collagen and Collagen Membrane Post-Tooth Extraction

https://pubmed.ncbi.nlm.nih.gov/18672985/

Xenograft versus extraction alone for ridge preservation after tooth removal

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

cairoU21677

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.