Abstract
Critical defects of the mandibular bone are very difficult to manage with currently available materials and technology. In the present work, we generated acellular and cellular substitutes for human bone by tissue engineering using nanostructured fibrin-agarose biomaterials, with and without adipose-tissue-derived mesenchymal stem cells differentiated to the osteogenic lineage using inductive media. Then, these substitutes were evaluated in an immunodeficient animal model of severely critical mandibular bone damage in order to assess the potential of the bioartificial tissues to enable bone regeneration. The results showed that the use of a cellular bone substitute was associated with a morpho-functional improvement of maxillofacial structures as compared to negative controls. Analysis of the defect site showed that none of the study groups fully succeeded in generating dense bone tissue at the regeneration area. However, the use of a cellular substitute was able to improve the density of the regenerated tissue (as determined via CT radiodensity) and form isolated islands of bone and cartilage. Histologically, the regenerated bone islands were comparable to control bone for alizarin red and versican staining, and superior to control bone for toluidine blue and osteocalcin in animals grafted with the cellular substitute. Although these results are preliminary, cellular fibrin-agarose bone substitutes show preliminary signs of usefulness in this animal model of severely critical mandibular bone defect.
Highlights
Several conditions and diseases may significantly affect the oral and maxillofacial region, including congenital malformations, trauma, infection, tumors, osteonecrosis, and other relevant pathologies [1] that can lead to significant loss of bone tissue [2]
Several types of biomaterials based on calcium phosphate bioformulations—especially tricalcium phosphate and hydroxyapatite—have been extensively used for the reconstruction of critical mandibular defects, with promising results [7,8,9], none of these biomaterials was fully efficient as an inductor of bone regeneration [10]
Promising results were described in rat calvarial defects using different types of biomaterials—such as hydroxyapatite combined with poly-lactic-co-glycolic acid [11], or composites containing wollastonite and β-tricalcium phosphate [12]—especially when biomaterials were combined with bone morphogenetic proteins (BMPs) [13]
Summary
Several conditions and diseases may significantly affect the oral and maxillofacial region, including congenital malformations, trauma, infection, tumors, osteonecrosis, and other relevant pathologies [1] that can lead to significant loss of bone tissue [2]. Large critical-size defects affecting the mandible are very difficult to manage, due to the unique histological and physiological characteristics of this bone [3]. Several types of biomaterials based on calcium phosphate bioformulations—especially tricalcium phosphate and hydroxyapatite—have been extensively used for the reconstruction of critical mandibular defects, with promising results [7,8,9], none of these biomaterials was fully efficient as an inductor of bone regeneration [10]. Reports related to the treatment of large critical-size bone defects are rare, as these conditions are very difficult to treat, and results are typically suboptimal [10]. Large critical defects were treated with an allogeneic bone matrix impregnated in BMP combined with a titanium mesh, but bone induction was only found only in one-third of the patients [14]
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