Ricardo Fernández-Valadés Gámez, Belén Gironés-Camarasa, Antonio España-López, Miguel Alaminos, Cristina Blanco-Elices, Miguel Angel Martin-Piedra, Ricardo Fernández-Valadés, Ingrid Garzón, [Martin-Piedra,MA, Blanco-Elices,C, Garzón,I, Alaminos,M] Tissue Engineering Group, Department of Histology, Faculty of Medicine, University of Granada, Granada, Spain. [Martin-Piedra,MA, Alaminos,M, Fernández-Valadés,R] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Gironés-Camarasa,B, Fernández-Valadés,R] Division of Pediatric Surgery, University Hospital Virgen de las Nieves, Granada, Spain. [Gironés-Camarasa,B] Doctoral Program in Biomedicine, University of Granada, Granada, Spain. [España-López,A, Fernández-Valadés,R] Craniofacial Malformations and Cleft Lip and Palate Management Unit, University Hospital Virgen de las Nieves, Granada, Spain. [Fernández-Valadés Gámez,R] Division of Oral and Maxillofacial Surgery, San Pedro Hospital, La Rioja, Logroño, Spain., and This research was funded by the Spanish Plan Nacional de Investigación Científica, De sarrollo e Innovación Tecnológica (I+D+i), grants FIS PI18/0332, FIS PI18/0331, FIS PI21/0980, and ICI19/00024 (BIOCLEFT), from Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (co-financed by the European Regional Development Fund (ERDF-FEDER), 'Una manera de hacer Europa', European Union). Supported by grant PI-0442-2019 from the Consejería de Salud y Familias, Junta de Andalucía, Spain.
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., Spanish Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+i), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, European Regional Development Fund (ERDF-FEDER), Consejería de Salud y Familias, Junta de Andalucía, Spain