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. 2020 Sep 8;10(9):1774.
doi: 10.3390/nano10091774.

A New Polycaprolactone-Based Biomembrane Functionalized with BMP-2 and Stem Cells Improves Maxillary Bone Regeneration

Affiliations

A New Polycaprolactone-Based Biomembrane Functionalized with BMP-2 and Stem Cells Improves Maxillary Bone Regeneration

Céline Stutz et al. Nanomaterials (Basel). .

Abstract

Oral diseases have an impact on the general condition and quality of life of patients. After a dento-alveolar trauma, a tooth extraction, or, in the case of some genetic skeletal diseases, a maxillary bone defect, can be observed, leading to the impossibility of placing a dental implant for the restoration of masticatory function. Recently, bone neoformation was demonstrated after in vivo implantation of polycaprolactone (PCL) biomembranes functionalized with bone morphogenic protein 2 (BMP-2) and ibuprofen in a mouse maxillary bone lesion. In the present study, human bone marrow derived mesenchymal stem cells (hBM-MSCs) were added on BMP-2 functionalized PCL biomembranes and implanted in a maxillary bone lesion. Viability of hBM-MSCs on the biomembranes has been observed using the "LIVE/DEAD" viability test and scanning electron microscopy (SEM). Maxillary bone regeneration was observed for periods ranging from 90 to 150 days after implantation. Various imaging methods (histology, micro-CT) have demonstrated bone remodeling and filling of the lesion by neoformed bone tissue. The presence of mesenchymal stem cells and BMP-2 allows the acceleration of the bone remodeling process. These results are encouraging for the effectiveness and the clinical use of this new technology combining growth factors and mesenchymal stem cells derived from bone marrow in a bioresorbable membrane.

Keywords: biomembrane; bone regeneration; nanoreservoirs; smart implant; stem cells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Diagram of the electrospinning technique and scanning electron microscopy (SEM) observation of electrospun PCL fibers. (B) Diagram of the nanoreservoir functionalization technique and SEM observation of PCL fibers functionalized with BMP-2 (PCL/(chitosan/BMP-2)10, 200 ng/mL). Arrowheads indicate the nanoreservoirs containing BMP-2 observed with SEM.
Figure 2
Figure 2
(A) Colony forming unit fibroblasts test (CFU-F): staining with HE of CFU formed after 14 days in culture. Arrows indicate 2 colonies. (B) Osteogenic differentiation after 21 days in the osteogenic medium; the differentiated cells produced nodules of mineralization stained with Alizarin Red S (arrows). (C) Adipocyte differentiation after 21 days in an adipogenic medium. Differentiated cells produced lipid vacuoles stained with Oil Red O. (D) Chondrocyte differentiation of the micromasses of hBM-MSCs after 21 days. Alcian Blue visualized the glycosaminoglycans (GAGs) specifically present in the cartilage.
Figure 3
Figure 3
Biocompatibility of PCL and bioactive scaffold for hBM-MSCs after 7 days of culture. HE staining (A,B), LIVE/DEAD viability test (C,D) and SEM observation (E,F). PCL and BMP-2 were not toxic to hBM-MSCs.
Figure 4
Figure 4
Observation of maxillary bone lesion after 3D reconstruction (A) of X-ray microtomography images (B) and after histological staining with Gomori trichrome staining (C).
Figure 5
Figure 5
Observation of bone regeneration of the maxillary bone after 90 days of implantation of a PCL membrane functionalized with BMP-2 (AC,E) and non-functionalized (A,B,D,F) with hBM-MSCs. A 3D reconstruction (A) of frontal (B) and sagittal (C,D) sections of X-ray microtomography and Gomori trichrome staining (E,F).
Figure 6
Figure 6
Observation of bone regeneration of the maxillary bone after 120 days of implantation of a PCL membrane functionalized with BMP-2 (AC,E) and non-functionalized (A,B,D,F) with hBM-MSCs. A 3D reconstruction (A) of frontal (B) and sagittal (C,D) sections of X-ray microtomography and Gomori trichrome staining (E,F).
Figure 7
Figure 7
Observation of bone regeneration of the maxillary bone 150 days after implantation of a PCL membrane functionalized with BMP-2 (A,B,D) and non-functionalized (A,C,E) with hBM-MSCs. A 3D reconstruction (A) of frontal and sagittal sections of X-ray microtomography and after microtome cutting and Gomori trichrome staining (BE).

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