Mesenchymal Stem Cells of Different Origin-Seeded Bioceramic Construct in Regeneration of Bone Defect in Rabbit

Abstract

Bone marrow derived mesenchymal stem cells (BMSC) represent an attractive cell population for tissue engineering purpose. The objective of this study was to determine whether the addition of recombinant human bone morphogenetic protein (rhBMP-2) and insulin-like growth factor (IGF-1) to a silica-coated calcium hydroxyapatite (HASi) - rabbit bone marrow derived mesenchymal stem cell (rBMSC) construct promoted bone healing in a large segmental bone defect beyond standard critical -size radial defects (15mm) in rabbits. An extensively large 30mm long radial ostectomy was performed unilaterally in thirty rabbits divided equally in five groups. Defects were filled with a HASi scaffold only (group B); HASi scaffold seeded with rBMSC (group C); HASi scaffold seeded with rBMSC along with rhBMP-2 and IGF-1 in groups D and E respectively. The same number of rBMSC (five million cells) and concentration of growth factors rhBMP-2 (50µg) and IGF-1 (50µg) was again injected at the site of bone defect after 15 days of surgery in their respective groups. An empty defect served as the control group (group A). Radiographically, bone healing was evaluated at 7, 15, 30, 45, 60 and 90 days post implantation. Histological qualitative analysis with microCT (µ-CT), haematoxylin and eosin (H & E) and Masson’s trichrome staining were performed 90 days after implantation. All rhBMP-2-added constructs induced the formation of well-differentiated mineralized woven bone surrounding the HASi scaffolds and bridging bone/implant interfaces as early as eight weeks after surgery. Bone regeneration appeared to develop earlier with the rhBMP-2 constructs than with the IGF-1 added construct. Constructs without any rhBMP-2 or IGF-1 showed osteoconductive properties limited to the bone junctions without bone ingrowths within the implantation site. In conclusion, the addition of rhBMP-2 to a HASi scaffold could promote bone generation in a large critical-size-defect.

Hydroxylapatite-collagen hybrid scaffold induces human adipose-derived mesenchymal stem cells to osteogenic differentiation in vitro and bone regrowth in patients

“…Previous studies reported that the pivot role, for hASCs osteogenic differentiation, is played by the HA, whereas the collagen mainly supports the survival, proliferation, and chondrogenic differentiation …”

Mesenchymal Stem Cells Derived from Rat Bone Marrow (rBM MSC): Techniques for Isolation, Expansion and Differentiation

“…21,22 Stem cell seeded biomaterials are now used routinely for different surgical affections. 23,24 The primary implications of these research findings remained unnoticed until recently. Commitment and differentiation are not usually thought of as reversible, but rather as multistep, unidirectional and terminal processes.…”

Repair of a critical‐size segmental rabbit femur defect using bioglass‐β‐TCP monoblock, a vascularized periosteal flap and BMP‐2

“…Nau et al demonstrated that combining a vascularized periosteal flap with a β‐TCP scaffold and bone marrow‐derived mononuclear cells resulted in improved bone healing in a similar rat femur model. The use of a rabbit radial or ulnar segmental diaphyseal defect model (10, 12, 15, 20, or 30 mm long) can be another good choice . Although there is no need for internal fixation in this model, it should be noted that this type of model cannot allow the animal to apply a mechanical load through the defect.…”

“…The use of a rabbit radial or ulnar segmental diaphyseal defect model (10,12,15,20, or 30 mm long) can be another good choice. [20][21][22][23] Although there is no need for internal fixation in this model, it should be noted that this type of model cannot allow the animal to apply a mechanical load through the defect. In addition, the adjacent ulna or radius may interfere with the results of this model.…”

“…The time scale of evaluation is commonly limited to discrete time points at early stages in rabbit models depending on defect size and site, implanted material, and the parameters to be analyzed due to the relatively fast healing characteristics of rabbit models. Some studies evaluated bone repair outcomes using histological analyses at 4 and 8 weeks postoperative, 22,23 while other experiences evaluated repair effects at 4, 8 and 12 weeks postoperative. 27,28 Before choosing 4 and 8 weeks as time points for this study, its validity in previous experiments and relevance to the model under investigation were carefully assessed.…”