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

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. Methods: In this preclinical study, the performance of two bioengineered scaffolds, an hydrogel made of polyethylene glycol-chitosan (HyCh) and an hybrid core-shell combination of poly(L-lactic acid)/poly(\(\epsilon\)-caprolactone) and HyCh (PLA-PCL-HyCh), seeded with different concentrations of human mesenchymal stem cells (hMSCs) ( i.e. 1000, 2000, and 3000 cells/mm 3 ), 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 (2000 and 3000 cells/mm 3 ). The immunohistochemical profile showed significantly higher expression of both VEGF-A, in defects reconstructed with a PLA-PCL-HyCh, and osteopontin, in defects reconstructed with both scaffolds. Native microarchitectural characteristics were not demonstrated in any experimental group. Conclusions: 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.