Abstract
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. 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®. Conclusion: Our results provide a proof-of-concept that adipose-based hypertrophic cartilage grafts outperform clinical standard biomaterials in maxillofacial surgery.
Highlights
Micro-CT demonstrated reproducible endochondral ossification (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 origin
The devitalized bone matrix (DBM) is not intrinsically osteogenic, and the bone repair is highly dependent on the presence of healthy bone in the vicinity of the bone defect to treat (Wu et al, 2011; Prince et al, 2019)
Since monolayer expansion and passaging of adipose-derived stromal cells (ASCs) was known to decrease their differentiation potential (Di Maggio et al, 2017), we reported that expansion and differentiation of ASCs directly inside their native, human adipose tissue can be used to generate hypertrophic cartilaginous constructs, referred to as hypertrophic Adiscaf, able to better form bone by ECO than expanded ASCs loaded in a sponge (Guerrero et al, 2018)
Summary
The structural stability and appearance of the face are mainly dependent on bone structure (Zhang and Yelick, 2018). The DBM is not intrinsically osteogenic, and the bone repair is highly dependent on the presence of healthy bone in the vicinity of the bone defect to treat (Wu et al, 2011; Prince et al, 2019) In this context, engineered osteoinductive and/or osteogenic tissues might have the potential to more closely mimic autologous bone grafts and result in comparable clinical performance. Devitalized bone matrix (DBM) is currently the gold standard alternative to autologous bone grafting in maxillofacial surgery It fully relies on its osteoconductive properties and 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 compared in an orthotopic, preclinical mandibular defect model in rat
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