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

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.

ATF2-driven osteogenic activity of enoxaparin sodium-loaded polymethylmethacrylate bone cement in femoral defect regeneration

“…The area was rinsed with normal saline to manage bone debris and heat from drilling. In vivo micro-CT scanning was performed on the 56 th day after surgery, and the repair of the femoral defects was evaluated by combining it with histological analysis [ 44 , 45 ]. As illustrated in Additional file 2 : Fig.…”

Engineered phalangeal grafts for children with symbrachydactyly: A proof of concept

“…Therefore, it represents an attractive source of mesenchymal stromal progenitors contained within the stromal vascular fraction (SVF) of the adipose tissue. 36 , 37 The potential use of SVF cells and their expanded progeny (ASCs) for bone regeneration following an ECO pathway has been demonstrated by our group both in ectopic 20 , 21 , 23 , 24 and orthotopic 38 settings but so far only with material obtained from adult individuals.…”

Efficient bone regeneration of BMP9-stimulated human periodontal ligament stem cells (hPDLSCs) in decellularized bone matrix (DBM) constructs to model maxillofacial intrabony defect repair

“…However, the limited source, donor site morbidity, immune rejection and laborious procedures hamper bone graft applications [4][5][6]. Recently, the use of tissue engineering strategies represents a promising alternative approach [7,8]. With the increased exploration of various seed cells and biological factors, which could be candidates for bone regeneration, the optimal combinations should be effectively determined for regenerative medicine.…”