AUTHOR=Ferrari Marco , Taboni Stefano , Chan Harley H. L. , Townson Jason , Gualtieri Tommaso , Franz Leonardo , Ruaro Alessandra , Mathews Smitha , Daly Michael J. , Douglas Catriona M. , Eu Donovan , Sahovaler Axel , Muhanna Nidal , Ventura Manuela , Dey Kamol , Pandini Stefano , Pasini Chiara , Re Federica , Bernardi Simona , Bosio Katia , Mattavelli Davide , Doglietto Francesco , Joshi Shrinidh , Gilbert Ralph W. , Nicolai Piero , Viswanathan Sowmya , Sartore Luciana , Russo Domenico , Irish Jonathan C. 

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

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2024.1353523

DOI=10.3389/fbioe.2024.1353523

ISSN=2296-4185

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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 (<inline-formula id="inf1"><mml:math id="m1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>ε</mml:mi></mml:mrow></mml:math></inline-formula>-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 <italic>in vivo</italic> radiological examinations and <italic>ex vivo</italic> radiological, histomorphological, and immunohistochemical analyses.</p><p><bold>Results:</bold> 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.</p><p><bold>Conclusion:</bold> 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.</p>