Repair of a Rat Mandibular Bone Defect by Hypertrophic Cartilage Grafts Engineered From Human Fractionated Adipose Tissue

利用人类脂肪组织制成的增生性软骨移植修复大鼠下颌骨缺损

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作者:Chen Cheng, Mansoor Chaaban, Gordian Born, Ivan Martin, Qingfeng Li, Dirk J Schaefer, Claude Jaquiery, Arnaud Scherberich

Background

Devitalized bone matrix (DBM) is currently the gold standard alternative to autologous bone grafting in maxillofacial surgery. However, it fully relies on its osteoconductive properties and therefore requires defects with healthy bone surrounding. Fractionated human adipose tissue, when differentiated into hypertrophic cartilage in vitro, was proven reproducibly osteogenic in vivo, by recapitulating endochondral ossification (ECO). Both types of bone substitutes were thus compared in an orthotopic, preclinical mandibular defect model in rat.

Conclusion

Our results provide a proof-of-concept that adipose-based hypertrophic cartilage grafts outperform clinical standard biomaterials in maxillofacial surgery.

Methods

Human adipose tissue samples were collected and cultured in vitro to generate disks of hypertrophic cartilage. After hypertrophic induction, eight samples from two donors were implanted into a mandible defect in rats, in parallel to Bio-Oss® DBM granules. After 12 weeks, the mandible samples were harvested and evaluated by Micro-CT and histology.

Results

Micro-CT demonstrated reproducible ECO and complete restoration of the mandibular geometry with adipose-based disks, with continuous bone inside and around the defect, part of which was of human (donor) origin. In the Bio-Oss® group, instead, osteoconduction from the border of the defect was observed but no direct connection of the granules with the surrounding bone was evidenced. Adipose-based grafts generated significantly higher mineralized tissue volume (0.57 ± 0.10 vs. 0.38 ± 0.07, n = 4, p = 0.03) and newly formed bone (18.9 ± 3.4% of surface area with bone tissue vs. 3 ± 0.7%, p < 0.01) than Bio-Oss®.

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