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

Abstract

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.

Thymoquinone loading into hydroxyapatite/alginate scaffolds accelerated the osteogenic differentiation of the mesenchymal stem cells

“…Due to availability, cheapness and biocompatibility, alginate is considered as popular drug vehicles that postpone or regulate the release of drugs from HA scaffolds [ 25 ]. Alginate also is a good vehicle for stem cell transplantation and therapy [ 26 ]. Besides the role of alginate as a carrier, it boosted the osteogenic impact of HA [ 27 ].…”

“…Besides the role of alginate as a carrier, it boosted the osteogenic impact of HA [ 27 ]. Rat hard cleft palate model also treated with alginate-based hydrogel [ 26 ]. Alginate in combination with HA and chitosan has been reported to provide a suitable drug delivery system in bone tissue engineering [ 28 ].…”

Compositions and Structural Geometries of Scaffolds Used in the Regeneration of Cleft Palates: A Review of the Literature

“…This demonstrated the potential of this new biomaterial for use as a bone substitute graft material for cleft palate repair. In addition, the biocompatibility of the alginate-based hydrogel and the actual benefits for tissue healing were verified [ 87 ].…”

Use of stem cells in bone regeneration in cleft palate patients: review and recommendations

“…Hydrogels also have been used for cleft palate closure. In a study by Naudot et al 37 using a group of allogenic BMMSCs with alginate-based hydrogel scaffolds, bone formation is observed in the middle of the implant in addition to in the margins. However, the rate of mineralization in the scaffold-only group is higher in the 8th and 12th week.…”