Microfragmented Fat and Biphasic Calcium Phosphates for Alveolar Cleft Repair: Protocol for a Prospective, Nonblinded, First-in-Human Clinical Study

Diandra Sabrina Natsir Kalla*, Salem Alkaabi, Abul Fauzi, Andi Tajrin, Rifaat Nurrahma, Werner E.G. Müller, Heinz C. Schröder, Xiaohong Wang, Tymour Forouzanfar, Marco N. Helder, Muhammad Ruslin

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Background: Biphasic calcium phosphates (BCP) may serve as off-the-shelf alternatives for iliac crest-derived autologous bone in alveolar cleft reconstructions. To add osteoinductivity to the osteoconductive BCPs to achieve similar regenerative capacity as autologous bone, a locally harvested buccal fat pad will be mechanically fractionated to generate microfragmented fat (MFAT), which has been shown to have high regenerative capacity due to high pericyte and mesenchymal stem cell content and a preserved perivascular niche. Objective: Our primary objectives will be to assess the feasibility and safety of the BCP-MFAT combination. The secondary objective will be efficacy, which will be evaluated using radiographic imaging and histological and histomorphometric evaluation of biopsies taken 6 months postoperatively, concomitant with dental implant placement. Methods: Eight patients with alveolar cleft (≥15 years) will be included in this prospective, nonblinded, first-in-human clinical study. MFAT will be prepared intraoperatively from the patient’s own buccal fat pad. Regular blood tests and physical examinations will be conducted, and any adverse events (AEs) or serious EAs (SAEs) will be meticulously recorded. Radiographic imaging will be performed prior to surgery and at regular intervals after reconstruction of the alveolar cleft with the BCP-MFAT combination. Biopsies obtained after 6 months with a trephine drill used to prepare the implantation site will be assessed with histological and histomorphometric analyses after methylmethacrylate embedding and sectioning. Results: The primary outcome parameter will be safety after 6 months’ follow-up, as monitored closely using possible occurrences of SAEs based on radiographic imaging, blood tests, and physical examinations. For efficacy, radiographic imaging will be used for clinical grading of the bone construct using the Bergland scale.

JMIR Res Protoc 2024 | vol. 13 | e42371 | p.

volume, graft volume, and number of osteoclasts will be histomorphometrically quantified. Recruitment started in November 2019, and the trial is currently in the follow-up stage. This protocol’s current version is 1.0, dated September 15, 2019. Conclusions: In this first-in-human study, not only safety but also the histologically and radiographically assessed regenerative potential of the BCP-MFAT combination will be evaluated in an alveolar cleft model. When an SAE occurs, it will be concluded that the BCP-MFAT combination is not yet safe in the current setting. Regarding AEs, if they do not occur at a higher frequency than that in patients treated with standard care (autologous bone) or can be resolved by noninvasive conventional methods (eg, with analgesics or antibiotics), the BCP-MFAT combination will be considered safe. In all other cases, the BCP-MFAT combination will not yet be considered safe.

Original languageEnglish
Article numbere42371
Pages (from-to)1-9
Number of pages9
JournalJMIR Research Protocols
Volume13
Issue number1
Early online date15 Jan 2024
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2024 JMIR Publications Inc.. All rights reserved.

Funding

We would like to thank Nisrina Ekayani N, DDS, and Citra Dewi Sahrir, DDS, for helping in the administrative process of receiving ethical approval. DSNK received a scholarship from the Indonesia Endowment Fund for Education (LPDP), Ministry of Finance, Republic of Indonesia.

FundersFunder number
Citra Dewi Sahrir
Diabetes-Stiftung
Kementerian Keuangan Republik Indonesia

    Keywords

    • alveolar
    • alveolar cleft
    • autograft
    • bone
    • bone grafting
    • bone regeneration
    • calcium phosphate
    • dental
    • dentistry
    • graft
    • jaw
    • maxillofacial
    • microfragmented fat
    • mouth
    • operation
    • oral
    • oral pathology
    • oral surgery
    • osteo
    • osteoconductive biphasic calcium phosphate
    • perioperative
    • regenerative medicine
    • surgery
    • surgical
    • teeth
    • tooth

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