Experimental Study on Reconstruction of Segmental Mandible Defects Using Tissue Engineered Bone Combined Bone Marrow Stromal Cells With Three-Dimensional Tricalcium Phosphate

Abstract

Reconstructive procedures of segmental mandible defects often require bone graft harvesting, which results in donor site morbidity; the use of tissue-engineered bone might mitigate this problem. The aim of the present experimental pilot study was to produce three-dimensional (3D) autologous tissue-engineered constructs that combine autogenous cultivated bone marrow stromal cells with beta-tricalcium phosphate to reconstruct segmental mandible defects without donor site morbidity. Bone marrow stromal cells were isolated from a dog's caput femoris. After differentiation and proliferation in vitro, the cells were seeded into a 3D beta-tricalcium phosphate scaffold. The constructs were incubated under osteogenic culture conditions for 5 days. Segmental defects of 30 mm length were created unilaterally in the mandibles of the animals. Reconstruction was performed using the construct in three dogs and the scaffold only in three dogs as a control group. The specimens were retrieved 3 months later, and the reconstructed areas were processed for gross observation, radiographic examination, 3D computed tomographic (CT) imaging, biomechanical evaluations, and histologic observation. The construct implanted group (n = 3) showed an average height of the reconstructed area of 18.54 mm and the control group 9.16 mm (P < 0.05). Higher radiodensity was present in the construct group than in the control group, as shown by radiograph. 3D CT imaging showed nearly two-thirds absorption of the reconstructed area in the control group. The biomechanical examination of the construct and control groups showed a compression strength of 102.77 N and 42.90 N and stress of 3.504 N/mm and 1.930 N/mm, which demonstrates significant difference. Histologic micrographs showed new bone formation in the scaffolds in central sections of the defects in the construct group 3 months later, with osteoblast seams, osteoclastic resorption, and cartilage formation. The construct of morphologic, 3D beta-tricalcium phosphate scaffold seeded, autologous bone marrow stromal cells ensure bone formation and vascularization throughout the procedure of mandible segmental defect reconstruction, closely resembling how tissue engineering would be used to reconstruct a segmental mandible defect in the clinical setting.

Tissue-Engineered Mandibular Bone Reconstruction for Continuity Defects: A Systematic Approach to the Literature

“…Another example is the 3 months data. 25 Their statistically significant better biomechanical results ( p < 0.05) for tissue-engineered bone as compared with the scaffold alone originate from not more than three animals/segmental defects. Thus, with an assumed a-error of 0.05, post hoc analysis for, for example, compression strength reveals a statistical power as low as 0.385.…”

“…In summary, autogenous bone precursor cells or autogenous osteogenic tissues were primarily combined with calcium phosphate ceramic scaffolds, such as beta-tri calcium phosphate (b-TCP) 4,11,25,26,106 and biphasic calcium phosphate ceramic, 26 or pyrolized bovine bone 100 or calcium carbonate, such as natural corals. 10,105 Considering the primary outcome variable bone bridging 4,11,18,26,[104][105][106][107]117 as well as the co-outcome variables bone ingrowth 100 and biomechanical testing, 4,10,25 autogenous bone precursor cells or autogenous tissues seeded onto calcium phosphate ceramic scaffolds showed in preclinical animal studies the potential of an alternative to autograft bone for mandibular bone reconstruction in continuity defects.…”

“…Furthermore, these scaffolds should possess (3) suitable surface chemistry for cell attachment, proliferation, and differentiation, and (4) mechanical properties to match those of the tissues at the site of implantation. 9 At present, a multitude of scaffolds made of various material [10][11][12][13][14][15][16][17][18][19] in combination with bioactive substances or osteogenic bone marrow stromal cells (BMSCs) 10,[20][21][22][23][24][25][26] to initiate or enhance bone formation [15][16][17]19,[27][28][29][30][31][32][33] are under study. In 2006, Ikada defined a concept on methodology in tissue engineering as (1) placing the construct scaffold in a bioreactor to reconstruct an engineered tissue in vitro called in vitro (or ex vivo) tissue engineering and (2) implantation of the construct scaffold in the body until a new tissue is regenerated in vivo called in vivo (or in situ) tissue engineering.…”

Biomechanics of mandibular reconstruction: a review

“…Using a finite element model, KORIOTH et al 29 calculated the maximal deformation of the mandible to be approximately 0.6 mm in a simulated unilateral molar bite of 526 N. They observed the helical deformation of the mandible upward and toward the working side during this simulated bite, with regions experiencing high magnitudes of tensile stress (15-25 MPa) running down and forward buccally and lingually from the anterior aspect of the coronoid processes and rami to meet at the lingual surface of the symphysis. The highest values of compressive stress (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) were found at the bite point and both sigmoid notches, at the working side mandibular angle, and in an area running from the posterior aspect of the balancing side ramus along the lower border of the body to the lower symphysis and up along the buccal aspect of the alveolar bone to the bite point. The shear stresses were generally larger on the working side, although the peak shear stress value of 25 MPa was found on the condyle of the balancing side.…”

Composite Mandibulectomy: A Novel Animal Model

“…For example, the canine, primate, and rabbit model have been described and appear to be effective representatives of the mandibular resection itself. [14][15][16][17] Unfortunately, a significant feature of many segmental resections of the mandible is the presence of intraoral continuity at the defect site prior to mucosal closure. Despite meticulous mucosal closure or soft-tissue reconstruction, perioperative salivary contamination may potentially occur if an intraoral defect is created during the course of the procedure.…”