PMID- 38224475 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240201 IS - 1929-0748 (Print) IS - 1929-0748 (Electronic) IS - 1929-0748 (Linking) VI - 13 DP - 2024 Jan 15 TI - Microfragmented Fat and Biphasic Calcium Phosphates for Alveolar Cleft Repair: Protocol for a Prospective, Nonblinded, First-in-Human Clinical Study. PG - e42371 LID - 10.2196/42371 [doi] LID - e42371 AB - 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. In addition, bone parameters such as bone volume, osteoid 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. TRIAL REGISTRATION: Indonesia Clinical Trial Registry INA-EW74C1N; https://tinyurl.com/28tnrr64. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42371. CI - (c)Diandra Sabrina Natsir Kalla, Salem Alkaabi, Abul Fauzi, Andi Tajrin, Rifaat Nurrahma, Werner E G Muller, Heinz C Schroder, Xiaohong Wang, Tymour Forouzanfar, Marco N Helder, Muhammad Ruslin. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 15.01.2024. FAU - Natsir Kalla, Diandra Sabrina AU - Natsir Kalla DS AUID- ORCID: 0000-0002-8274-3486 AD - Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands. AD - Department of Biochemistry, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. FAU - Alkaabi, Salem AU - Alkaabi S AUID- ORCID: 0000-0001-9450-6413 AD - Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands. AD - Department of Oral and Maxillofacial Surgery, Fujairah Hospital, Ministry of Health, Fujairah, United Arab Emirates. FAU - Fauzi, Abul AU - Fauzi A AUID- ORCID: 0000-0001-7050-4878 AD - Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia. FAU - Tajrin, Andi AU - Tajrin A AUID- ORCID: 0000-0002-4186-7968 AD - Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia. FAU - Nurrahma, Rifaat AU - Nurrahma R AUID- ORCID: 0000-0003-4356-2022 AD - Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands. AD - Department of Prosthodontics, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia. FAU - Muller, Werner E G AU - Muller WEG AUID- ORCID: 0000-0002-8223-3689 AD - ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany. FAU - Schroder, Heinz C AU - Schroder HC AUID- ORCID: 0000-0003-0992-6427 AD - ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany. FAU - Wang, Xiaohong AU - Wang X AUID- ORCID: 0000-0003-1796-6314 AD - ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany. FAU - Forouzanfar, Tymour AU - Forouzanfar T AUID- ORCID: 0000-0001-7942-8533 AD - Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands. AD - Department of Oral and Maxillofacial Surgery, Leiden University Medical Centre, Leiden, Netherlands. FAU - Helder, Marco N AU - Helder MN AUID- ORCID: 0000-0003-3195-1223 AD - Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands. FAU - Ruslin, Muhammad AU - Ruslin M AUID- ORCID: 0000-0003-0943-4000 AD - Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia. LA - eng PT - Journal Article DEP - 20240115 PL - Canada TA - JMIR Res Protoc JT - JMIR research protocols JID - 101599504 PMC - PMC10825761 OTO - NOTNLM OT - alveolar OT - alveolar cleft OT - autograft OT - bone OT - bone grafting OT - bone regeneration OT - calcium phosphate OT - dental OT - dentistry OT - graft OT - jaw OT - maxillofacial OT - microfragmented fat OT - mouth OT - operation OT - oral OT - oral pathology OT - oral surgery OT - osteo OT - osteoconductive biphasic calcium phosphate OT - perioperative OT - regenerative medicine OT - surgery OT - surgical OT - teeth OT - tooth COIS- Conflicts of Interest: None declared. EDAT- 2024/01/15 12:42 MHDA- 2024/01/15 12:43 PMCR- 2024/01/15 CRDT- 2024/01/15 11:52 PHST- 2022/09/02 00:00 [received] PHST- 2023/02/09 00:00 [accepted] PHST- 2023/02/08 00:00 [revised] PHST- 2024/01/15 12:43 [medline] PHST- 2024/01/15 12:42 [pubmed] PHST- 2024/01/15 11:52 [entrez] PHST- 2024/01/15 00:00 [pmc-release] AID - v13i1e42371 [pii] AID - 10.2196/42371 [doi] PST - epublish SO - JMIR Res Protoc. 2024 Jan 15;13:e42371. doi: 10.2196/42371.