Hydrogel-chitosan and polylactic acid-polycaprolactone bioengineered scaffolds for reconstruction of mandibular defects: a preclinical in vivo study with assessment of translationally relevant aspects

水凝胶-壳聚糖和聚乳酸-聚己内酯生物工程支架用于重建下颌骨缺损:一项评估转化相关方面的临床前体内研究

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作者:Marco Ferrari #, Stefano Taboni #, Harley H L Chan, Jason Townson, Tommaso Gualtieri, Leonardo Franz, Alessandra Ruaro, Smitha Mathews, Michael J Daly, Catriona M Douglas, Donovan Eu, Axel Sahovaler, Nidal Muhanna, Manuela Ventura, Kamol Dey, Stefano Pandini, Chiara Pasini, Federica Re, Simona Berna

Background

Reconstruction of mandibular bone defects is a surgical challenge, and microvascular reconstruction is the current gold standard. The field of tissue bioengineering has been providing an increasing number of alternative strategies for bone reconstruction.

Conclusion

Herein, we demonstrate that bone regeneration can be boosted by scaffold- and seeded scaffold-reconstruction, achieving, respectively, 50% and 70% restoration of presurgical bone density in 120 days, compared to 40% restoration seen in spontaneous regeneration. Although optimization of the regenerative performance is needed, these results will help to establish a baseline reference for future experiments.

Methods

In this preclinical study, the performance of two bioengineered scaffolds, a hydrogel made of polyethylene glycol-chitosan (HyCh) and a hybrid core-shell combination of poly (L-lactic acid)/poly ( εε<math><mrow><mi>ε</mi></mrow> </math> -caprolactone) and HyCh (PLA-PCL-HyCh), seeded with different concentrations of human mesenchymal stromal cells (hMSCs), has been explored in non-critical size mandibular defects in a rabbit model. The bone regenerative properties of the bioengineered scaffolds were analyzed by in vivo radiological examinations and ex vivo radiological, histomorphological, and immunohistochemical analyses.

Results

The relative density increase (RDI) was significantly more pronounced in defects where a scaffold was placed, particularly if seeded with hMSCs. The immunohistochemical profile showed significantly higher expression of both VEGF-A and osteopontin in defects reconstructed with scaffolds. Native microarchitectural characteristics were not demonstrated in any experimental group.

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