Usefulness of a Nanostructured Fibrin-Agarose Bone Substitute in a Model of Severely Critical Mandible Bone Defect

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.

Dentin slice model of dental stem cells in a fibrin-agarose construct for dental pulp regeneration

“…Previous studies reported fibrin-agarose as a biological substitute with applications on artificial tissues such as cornea, 23 among others. This study showed that the fibrin-agarose construct formed a three-dimensional structure of such consistency that allowed easy manipulation and consistency that facilitated the incorporation of MSCs.…”

Technological advances in fibrin for tissue engineering

“…Martin-Piedra et al developed nanostructured fibrin-agarose biomaterials to produce bone substitutes with and without adipose-derived mesenchymal stem cells in immunodeficient animal models, improving the morphofunctional aspects of their maxillofacial structures. 205 A preliminary analysis determined that these cellular substitutes could improve the density of the regenerated tissue and provide isolated islands of bone and cartilage. There are preliminary signs that cellular fibrin-agarose substitutes are useful for the treatment of severely critical mandibular bone defects.…”