The combination of a poly-caprolactone/nano-hydroxyapatite honeycomb scaffold and mesenchymal stem cells promotes bone regeneration in rat calvarial defects.

Bone tissue engineering goes beyond the limitations of conventional methods of treating bone loss, such as autograft-induced morbidity and a lack of integration for large grafts. Novel biomimicry approaches (using three-dimensional [3D] electrospinning and printing techniques) have been designed to offer the most appropriate environment for cells and thus promote bone regeneration. In the present study, we assessed the bone regeneration properties of a composite 3D honeycomb structure from the electrostatic template-assisted deposition process by an alternate deposition of electrospun polycaprolactone (PCL) nanofibers and electrosprayed hydroxyapatite nanoparticles (nHA) on a honeycomb micropatterned substrate. We first confirmed the cytocompatibility of this honeycomb PCL-nHA scaffold in culture with bone marrow-derived mesenchymal stem cells (BM-MSCs). The scaffold was then implanted (alone or with seeded MSCs) for 2 months in a rat critical-sized calvarial defect model. The observation of new bone synthesis in situ (monitored using microcomputed tomography every 2 weeks and a histological assessment upon extraction) demonstrated that the honeycomb PCL-nHA scaffold was osteoconductive. Moreover, the combination of the scaffold with BM-MSCs was associated with significantly greater bone volume and mineralized regeneration during the 2-month experiment. The combination of the biomimetic honeycomb PCL-nHA scaffold with patient mesenchymal stem cells might therefore have great potential for clinical applications and specifically in maxillofacial surgery.

Functional Validation of a New Alginate-based Hydrogel Scaffold Combined with Mesenchymal Stem Cells in a Rat Hard Palate Cleft Model.

BACKGROUND: One of the major difficulties in cleft palate repair is the requirement for several surgical procedures and autologous bone grafting to form a bony bridge across the cleft defect. Engineered tissue, composed of a biomaterial scaffold and multipotent stem cells, may be a useful alternative for minimizing the non-negligible risk of donor site morbidity. The present study was designed to confirm the healing and osteogenic properties of a novel alginate-based hydrogel in palate repair. METHODS: Matrix constructs, seeded with allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) or not, were incorporated into a surgically created, critical-sized cleft palate defect in the rat. Control with no scaffold was also tested. Bone formation was assessed using microcomputed tomography at weeks 2, 4, 8, and 12 and a histologic analysis at week 12. RESULTS: At 12 weeks, the proportion of bone filling associated with the use of hydrogel scaffold alone did not differ significantly from the values observed in the scaffold-free experiment (61.01% ± 5.288% versus 36.91% ± 5.132%; p = 0.1620). The addition of BM-MSCs stimulated bone formation not only at the margin of the defect but also in the center of the implant. CONCLUSIONS: In a relevant in vivo model of cleft palate in the rat, we confirmed the alginate-based hydrogel's biocompatibility and real advantages for tissue healing. Addition of BM-MSCs stimulated bone formation in the center of the implant, demonstrating the new biomaterial's potential for use as a bone substitute grafting material for cleft palate repair.