Abstract
PurposeAutologous bone grafting (BG) remains the standard reconstruction strategy for large craniofacial defects. Calcium phosphate (CaP) biomaterials, such as biphasic calcium phosphate (BCP), do not yield consistent results when used alone and must then be combined with cells through bone tissue engineering (BTE). In this context, total bone marrow (TBM) and bone marrow-derived mesenchymal stem cells (MSC) are the primary sources of cellular material used with biomaterials. However, several other BTE strategies exist, including the use of growth factors, various scaffolds, and MSC isolated from different tissues. Thus, clinicians might be unsure as to which method offers patients the most benefit. For this reason, the aim of this study was to compare eight clinically relevant BTE methods in an “all-in-one” study.MethodsWe used a transgenic rat strain expressing green fluorescent protein (GFP), from which BG, TBM, and MSC were harvested. Progenitor cells were then mixed with CaP materials and implanted subcutaneously into nude mice. After eight weeks, bone formation was evaluated by histology and scanning electron microscopy, and GFP-expressing cells were tracked with photon fluorescence microscopy.Results/ConclusionsBone formation was observed in only four groups. These included CaP materials mixed with BG or TBM, in which abundant de novo bone was formed, and BCP mixed with committed cells grown in two- and three-dimensions, which yielded limited bone formation. Fluorescence microscopy revealed that only the TBM and BG groups were positive for GFP expressing-cells, suggesting that these donor cells were still present in the host and contributed to the formation of bone. Since the TBM-based procedure does not require bone harvest or cell culture techniques, but provides abundant de novo bone formation, we recommend consideration of this strategy for clinical applications.
Highlights
Bone reconstruction might be required in patients with craniofacial defects or following resection of oral carcinomas
At day 14, the relative expression levels of osteogenic genes (Alpl, Bglap, and Runx2) for cells grown in osteogenic medium (OM) showed a respective 4, 2, and 2.5 fold increase compared to the non-OM control (Fig. 2A)
At day 28, the relative expression levels of osteogenic genes (Alpl, Bglap, and Runx2) for cells grown in OM showed a respective 4, 3.5, and 18 fold increase compared to the non-OM control (Fig. 2D)
Summary
Bone reconstruction might be required in patients with craniofacial defects (e.g., craniofacial trauma or malformations) or following resection of oral carcinomas. Calcium phosphate (CaP) biomaterials, and biphasic calcium phosphate (BCP), have shown clinical efficacy in orthopedic surgery [6,7], avoiding second surgical site morbidity and reducing surgery time compared to autologous grafting [7,8]. Clinical applications must be restricted to small bone defects or to regions with significant bone contact [9] In view of these limitations, surgeons and researchers have focused on developing alternative therapies to BG over the past fifteen years. These mainly included combining osteoprogenitor cells with bone substitutes to improve their osteogenic properties. The efficacy of CaP biomaterials (i.e., granules, sticks, or blocks) combined with autologous bone marrow or autologous cancellous bone has been shown in clinical studies for defect filling in various orthopedic procedures [14]
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