Adipose stem cells used to reconstruct 13 cases with cranio-maxillofacial hard-tissue defects

Abstract

Although isolated reports of hard-tissue reconstruction in the cranio-maxillofacial skeleton exist, multipatient case series are lacking. This study aimed to review the experience with 13 consecutive cases of cranio-maxillofacial hard-tissue defects at four anatomically different sites, namely frontal sinus (3 cases), cranial bone (5 cases), mandible (3 cases), and nasal septum (2 cases). Autologous adipose tissue was harvested from the anterior abdominal wall, and adipose-derived stem cells were cultured, expanded, and then seeded onto resorbable scaffold materials for subsequent reimplantation into hard-tissue defects. The defects were reconstructed with either bioactive glass or β-tricalcium phosphate scaffolds seeded with adipose-derived stem cells (ASCs), and in some cases with the addition of recombinant human bone morphogenetic protein-2. Production and use of ASCs were done according to good manufacturing practice guidelines. Follow-up time ranged from 12 to 52 months. Successful integration of the construct to the surrounding skeleton was noted in 10 of the 13 cases. Two cranial defect cases in which nonrigid resorbable containment meshes were used sustained bone resorption to the point that they required the procedure to be redone. One septal perforation case failed outright at 1 year because of the postsurgical resumption of the patient's uncontrolled nasal picking habit.

Keywords: Adipose stem cells; Bioactive glass; Bone morphogenetic protein; β-Tricalcium phosphate.

Figure 1.

Collage of frontal sinus treatment. (A): 4′,6-diamidino-2-phenylindole nuclear staining image of bioactive glass granules seeded with adipose stem cells (BonAlive). Scale bar = 1 mm. (B): Alkaline phosphatase staining of a bioactive glass granule seeded with adipose stem cells (BonAlive). Scale bar = 1 mm. (C): Preoperative computed tomography (CT) scan of the left frontal sinus demonstrating mucosal changes and frontal sinusitis. (D): Clinical photograph of exposed diseased frontal sinus with purulent mucosa. (E): Clinical photograph of debrided frontal sinus packed with granules of bioactive glass seeded with autologous adipose-derived stem cells. (F): Postoperative CT scan of the frontal sinus obliterated with autologous adipose stem cell-seeded bioactive glass 28 months following surgery with no resorption of the construct.

Figure 2.

Collage of cranial defect cases. (A): Meningioma resection site filled with autologous adipose stem cell-seeded β-tricalcium phosphate (β-TCP) granules. (B): Titanium containment mesh on top of stem cell-seeded β-TCP granules to keep granules from migrating. (C): Immediate postoperative cranial computed tomography (CT) scan showing titanium containment mesh and adipose-derived stem cell-seeded β-TCP granular construct. (D): Postoperative cranial CT taken 28 months following surgery with signs of integration of the cranioplasty construct.

Figure 3.

Collage of mandibular reconstructions. (A): Virtual preoperative planning using Romexis software with computer-generated image of patient with large mandibular ameloblastoma showing the reconstruction plate over the area planned for resection from an anterior view. (B): Computer-generated image of patient with large mandibular ameloblastoma showing the reconstruction plate over the area planned for resection from a medial view. (C): Intraoperative photograph showing reconstruction plate in position and resection lines on mandibular ramus posteriorly and body anteriorly. (D): Intraoperative photograph with adipose-derived stem cell-seeded β-tricalcium phosphate (β-TCP) granular construct with recombinant human bone morphogenetic protein-2 (rhBMP-2) being placed beneath titanium containment mesh at mandibular resection site. (E): Postoperative three-dimensional (3D) computed tomography (CT) scan anterior view of the regenerated left body and ramus of the mandible 12 months after reconstruction. (F): Postoperative 3D CT scan basilar view of the regenerated left body and ramus of the mandible 12 months after reconstruction. (G): Cone beam CT scan showing mandibular reconstruction using autologous adipose-derived stem cell-seeded β-TCP granular construct with rhBMP-2 restored with successful functionally loaded dental implant in the regenerated bone.

Figure 4.

Collage of nasal septal perforation treatment. (A): Preoperative computed tomography (CT) scan in the sagittal plane revealing chronic nasal septal perforation before repair (arrow). (B): Intraoperative endoscopic view of chronic nasal septal perforation with margins incised. (C): Autologous adipose stem cell-seeded resorbable scaffold composed of β-tricalcium phosphate (β-TCP) and ε-polycaprolactone ready for implantation. (D): Intraoperative endoscopic view of implanted seeded scaffold sandwiched between two flaps closing the nasal septal perforation. (E): Postoperative CT scan showing chronic nasal septal perforation repaired with autologous adipose stem cell-seeded β-TCP strip construct (arrow).

Figure 5.

Column diagram on flow cytometry data of adipose-derived stem cells. Columns illustrate mean surface marker expression levels with standard deviation error bars of all patient samples.

Figure 6.

Postoperative cranioplasty radiographs. (A): Computed tomography (CT) image of cranioplasty with resorbable polylactic acid polymer-based mesh on the outer and inner cranium. (B): CT image of cranioplasty with resorbable polylactic acid polymer-based mesh with almost complete resorption of the autologous adipose-derived stem cell-seeded β-tricalcium phosphate-seeded construct.