Martin-Piedra Miguel-Angel, Gironés-Camarasa Belén, España-López Antonio, Fernández-Valadés Gámez Ricardo, Blanco-Elices Cristina, Garzón Ingrid, Alaminos Miguel, Fernández-Valadés Ricardo
Tissue Engineering Group, Department of Histology, Faculty of Medicine, University of Granada, E18016 Granada, Spain.
Instituto de Investigación Biosanitaria ibs.GRANADA, E18012 Granada, Spain.
Polymers (Basel). 2021 Nov 15;13(22):3939. doi: 10.3390/polym13223939.
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.
下颌骨的严重缺损目前很难用现有的材料和技术进行处理。在本研究中，我们利用纳米结构的纤维蛋白-琼脂糖生物材料通过组织工程技术制备了人骨的脱细胞和细胞替代物，其中一种含有经诱导培养基诱导分化为成骨谱系的脂肪组织来源的间充质干细胞，另一种不含。然后，在严重临界性下颌骨损伤的免疫缺陷动物模型中对这些替代物进行评估，以评估生物人工组织促进骨再生的潜力。结果表明，与阴性对照组相比，使用细胞骨替代物可使颌面结构在形态功能上得到改善。对缺损部位的分析表明，没有一个研究组能在再生区域完全成功地生成致密的骨组织。然而，使用细胞替代物能够提高再生组织的密度（通过CT放射密度测定），并形成孤立的骨和软骨岛。组织学上，在植入细胞替代物的动物中，再生骨岛的茜素红和多功能蛋白聚糖染色与对照骨相当，甲苯胺蓝和骨钙素染色优于对照骨。尽管这些结果是初步的，但细胞纤维蛋白-琼脂糖骨替代物在这种严重临界性下颌骨缺损的动物模型中显示出初步的有用迹象。
