Lateral Ramus Cortical Bone Plate in Alveolar Cleft Osteoplasty with Concomitant Use of Buccal Fat Pad Derived Cells and Autogenous Bone: Phase I Clinical Trial

Arash Khojasteh, Lida Kheiri, Hossein Behnia, Azita Tehranchi, Pantea Nazeman, Nasser Nadjmi, Masoud Soleimani, Arash Khojasteh, Lida Kheiri, Hossein Behnia, Azita Tehranchi, Pantea Nazeman, Nasser Nadjmi, Masoud Soleimani

Abstract

Tissue regeneration has become a promising treatment for craniomaxillofacial bone defects such as alveolar clefts. This study sought to assess the efficacy of lateral ramus cortical plate with buccal fat pad derived mesenchymal stem cells (BFSCs) in treatment of human alveolar cleft defects. Ten patients with unilateral anterior maxillary cleft met the inclusion criteria and were assigned to three treatment groups. First group was treated with anterior iliac crest (AIC) bone and a collagen membrane (AIC group), the second group was treated with lateral ramus cortical bone plate (LRCP) with BFSCs mounted on a natural bovine bone mineral (LRCP+BFSC), and the third group was treated with AIC bone, BFSCs cultured on natural bovine bone mineral, and a collagen membrane (AIC+BFSC). The amount of regenerated bone was measured using cone beam computed tomography 6 months postoperatively. AIC group showed the least amount of new bone formation (70 ± 10.40%). LRCP+BFSC group demonstrated defect closure and higher amounts of new bone formation (75 ± 3.5%) but less than AIC+BFSC (82.5 ± 6.45%), suggesting that use of BFSCs within LRCP cage and AIC may enhance bone regeneration in alveolar cleft bone defects; however, the differences were not statistically significant. This clinical trial was registered at clinicaltrial.gov with NCT02859025 identifier.

Figures

Figure 1
Figure 1
Consort flow diagram demonstrating study protocol.
Figure 2
Figure 2
Buccal fat pad harvesting. Buccal fat pad was exposed and harvested using a vestibular incision distal to the second molar.
Figure 3
Figure 3
Light microscopic evaluation of the stellate like cells extracted from buccal fat pad.
Figure 4
Figure 4
(a) SEM evaluation views of NBBM granule (×50); (b) BFSCs laid down into the scaffold through cellular pods and attachments at ×500 and ×1000 view (c).
Figure 5
Figure 5
Lateral ramus cortical bone was harvested from lateral side of the mandible.
Figure 6
Figure 6
Preparation and placing of LRCP; LRCP was trimmed and cut to 2-3 pieces and fixed in defect region. Protected healing space was created and BFSCs were delivered to the space.
Figure 7
Figure 7
Anterior iliac crest spongy bone was filled in the alveolar defect in control group and covered with collagen membrane.
Figure 8
Figure 8
Scaffolds carrying BFSCs covered the spongy iliac bone in AIC+BFSC group.
Figure 9
Figure 9
Flow cytometeric evaluation of the human buccal fat pad derived stem cells. CD 70, 93, 44, and 105 were detected positive and CD 45 and 34 were negative.
Figure 10
Figure 10
(a) Alizarin red staining. Nodule-like structures of mineralized matrix were observed under inverted light microscope. (b) Oil red staining revealed positive result for in vitro adipogenic differentiation.
Figure 11
Figure 11
Tomography of new bone formation in LRCP+BFSC. (b) Tomography of new bone formation in AIC+BFSC group. (c) Radiographic investigation of new bone formation in control group.
Figure 12
Figure 12
(a) Bone Healing after 9 months in LRCP group. (b) Dental Implant placement in new regenerate bone. (c) Healed alveolar cleft defects in AIC+BFSCs group. (d) Dental implant placement in new regenerate bone.
Figure 13
Figure 13
Normal bone with active osteoblasts producing osteoid matrix in the presence of a fibrous type marrow (H&E ×10). (a) Hematoxylin & eosin staining ×10, (b) ×40.

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