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
Guided Therapeutics (GTx) Program International Scholarship, University Health Network (UHN), Toronto, ON, Canada.
Section of Otorhinolaryngology-Head and Neck Surgery, Department of Neurosciences, University of Padua, Padua, Italy.
Front Bioeng Biotechnol. 2024 Jul 15;12:1353523. doi: 10.3389/fbioe.2024.1353523. eCollection 2024.
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. 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 ( -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 radiological examinations and radiological, histomorphological, and immunohistochemical analyses. 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. 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.
下颌骨缺损的重建是一项外科挑战，微血管重建是当前的金标准。组织生物工程领域一直在为骨重建提供越来越多的替代策略。在这项临床前研究中，已在兔模型的非临界尺寸下颌骨缺损中探索了两种生物工程支架的性能，一种是由聚乙二醇-壳聚糖制成的水凝胶（HyCh），另一种是聚（L-乳酸）/聚（ε-己内酯）与HyCh的混合核壳组合（PLA-PCL-HyCh），接种不同浓度的人间充质基质细胞（hMSCs）。通过放射学检查以及放射学、组织形态学和免疫组织化学分析来分析生物工程支架的骨再生特性。在放置了支架的缺损处，相对密度增加（RDI）更为明显，尤其是接种了hMSCs的情况。免疫组织化学分析表明，在用支架重建的缺损处，VEGF-A和骨桥蛋白的表达均显著更高。在任何实验组中均未显示出天然的微结构特征。在此，我们证明支架重建和接种支架重建均可促进骨再生，在120天内分别实现术前骨密度50%和70%的恢复，而自发再生仅为40%。尽管需要优化再生性能，但这些结果将有助于为未来的实验建立一个基线参考。
