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Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway.

Ho MH, Yao CJ, Liao MH, Lin PI, Liu SH, Chen RM - Int J Nanomedicine (2015)

Bottom Line: Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor.Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline phosphatase and osteocalcin gene expressions.Our results suggest the potential of chitosan nanofiber scaffolds for therapy of bone diseases, including bone defects and bone fractures.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan ; Cell Physiology and Molecular Image Research Center, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.

ABSTRACT
Osteoblasts play critical roles in bone formation. Our previous study showed that chitosan nanofibers can stimulate osteoblast proliferation and maturation. This translational study used an animal model of bone defects to evaluate the effects of chitosan nanofiber scaffolds on bone healing and the possible mechanisms. In this study, we produced uniform chitosan nanofibers with fiber diameters of approximately 200 nm. A bone defect was surgically created in the proximal femurs of male C57LB/6 mice, and then the left femur was implanted with chitosan nanofiber scaffolds for 21 days and compared with the right femur, which served as a control. Histological analyses revealed that implantation of chitosan nanofiber scaffolds did not lead to hepatotoxicity or nephrotoxicity. Instead, imaging analyses by X-ray transmission and microcomputed tomography showed that implantation of chitosan nanofiber scaffolds improved bone healing compared with the control group. In parallel, microcomputed tomography and bone histomorphometric assays further demonstrated augmentation of the production of new trabecular bone in the chitosan nanofiber-treated group. Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor. As to the mechanisms, analysis by confocal microscopy showed that implantation of chitosan nanofiber scaffolds increased levels of Runt-related transcription factor 2 (Runx2), a key transcription factor that regulates osteogenesis, in the bone defect sites. Successively, amounts of alkaline phosphatase and osteocalcin, two typical biomarkers that can simulate bone maturation, were augmented following implantation of chitosan nanofiber scaffolds. Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline phosphatase and osteocalcin gene expressions. Our results suggest the potential of chitosan nanofiber scaffolds for therapy of bone diseases, including bone defects and bone fractures.

No MeSH data available.


Related in: MedlinePlus

Improved effects of chitosan nanofiber scaffolds on bone healing.Notes: Bone defects were surgically created in the proximal femurs of male C57LB/L mice, and chitosan nanofibers were implanted into one defect for 21 days. Only one defect was created in each proximal femur of an animal. After that period, animals were sacrificed, and the femurs were collected for analysis by μCT. The trabecular bone number (A), trabecular bone thickness (B), and trabecular parameter factor (C) were calculated and statistically analyzed. Each value represents the mean ± SEM for n=9. *Indicates that values significantly differed from the respective control, P<0.05.Abbreviations: μCT, microcomputed tomography; SEM, standard error of mean.
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f5-ijn-10-5941: Improved effects of chitosan nanofiber scaffolds on bone healing.Notes: Bone defects were surgically created in the proximal femurs of male C57LB/L mice, and chitosan nanofibers were implanted into one defect for 21 days. Only one defect was created in each proximal femur of an animal. After that period, animals were sacrificed, and the femurs were collected for analysis by μCT. The trabecular bone number (A), trabecular bone thickness (B), and trabecular parameter factor (C) were calculated and statistically analyzed. Each value represents the mean ± SEM for n=9. *Indicates that values significantly differed from the respective control, P<0.05.Abbreviations: μCT, microcomputed tomography; SEM, standard error of mean.

Mentions: Parameters tested and acquired by μCT analyses were quantified and statistically analyzed in order to further verify the effects of chitosan nanofibers on stimulation of bone healing (Figure 5). Implantation of chitosan nanofiber scaffolds into the defect site caused a significant 24% increase in trabecular bone numbers (Figure 5A). In addition, the trabecular bone thickness was meaningfully augmented by 22% following implantation of chitosan nanofiber scaffolds (Figure 5B). In contrast, after administering chitosan nanofiber scaffolds into the bone defect site for 21 days, the TPF was reduced by 19% (Figure 5C).


Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway.

Ho MH, Yao CJ, Liao MH, Lin PI, Liu SH, Chen RM - Int J Nanomedicine (2015)

Improved effects of chitosan nanofiber scaffolds on bone healing.Notes: Bone defects were surgically created in the proximal femurs of male C57LB/L mice, and chitosan nanofibers were implanted into one defect for 21 days. Only one defect was created in each proximal femur of an animal. After that period, animals were sacrificed, and the femurs were collected for analysis by μCT. The trabecular bone number (A), trabecular bone thickness (B), and trabecular parameter factor (C) were calculated and statistically analyzed. Each value represents the mean ± SEM for n=9. *Indicates that values significantly differed from the respective control, P<0.05.Abbreviations: μCT, microcomputed tomography; SEM, standard error of mean.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590342&req=5

f5-ijn-10-5941: Improved effects of chitosan nanofiber scaffolds on bone healing.Notes: Bone defects were surgically created in the proximal femurs of male C57LB/L mice, and chitosan nanofibers were implanted into one defect for 21 days. Only one defect was created in each proximal femur of an animal. After that period, animals were sacrificed, and the femurs were collected for analysis by μCT. The trabecular bone number (A), trabecular bone thickness (B), and trabecular parameter factor (C) were calculated and statistically analyzed. Each value represents the mean ± SEM for n=9. *Indicates that values significantly differed from the respective control, P<0.05.Abbreviations: μCT, microcomputed tomography; SEM, standard error of mean.
Mentions: Parameters tested and acquired by μCT analyses were quantified and statistically analyzed in order to further verify the effects of chitosan nanofibers on stimulation of bone healing (Figure 5). Implantation of chitosan nanofiber scaffolds into the defect site caused a significant 24% increase in trabecular bone numbers (Figure 5A). In addition, the trabecular bone thickness was meaningfully augmented by 22% following implantation of chitosan nanofiber scaffolds (Figure 5B). In contrast, after administering chitosan nanofiber scaffolds into the bone defect site for 21 days, the TPF was reduced by 19% (Figure 5C).

Bottom Line: Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor.Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline phosphatase and osteocalcin gene expressions.Our results suggest the potential of chitosan nanofiber scaffolds for therapy of bone diseases, including bone defects and bone fractures.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan ; Cell Physiology and Molecular Image Research Center, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.

ABSTRACT
Osteoblasts play critical roles in bone formation. Our previous study showed that chitosan nanofibers can stimulate osteoblast proliferation and maturation. This translational study used an animal model of bone defects to evaluate the effects of chitosan nanofiber scaffolds on bone healing and the possible mechanisms. In this study, we produced uniform chitosan nanofibers with fiber diameters of approximately 200 nm. A bone defect was surgically created in the proximal femurs of male C57LB/6 mice, and then the left femur was implanted with chitosan nanofiber scaffolds for 21 days and compared with the right femur, which served as a control. Histological analyses revealed that implantation of chitosan nanofiber scaffolds did not lead to hepatotoxicity or nephrotoxicity. Instead, imaging analyses by X-ray transmission and microcomputed tomography showed that implantation of chitosan nanofiber scaffolds improved bone healing compared with the control group. In parallel, microcomputed tomography and bone histomorphometric assays further demonstrated augmentation of the production of new trabecular bone in the chitosan nanofiber-treated group. Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor. As to the mechanisms, analysis by confocal microscopy showed that implantation of chitosan nanofiber scaffolds increased levels of Runt-related transcription factor 2 (Runx2), a key transcription factor that regulates osteogenesis, in the bone defect sites. Successively, amounts of alkaline phosphatase and osteocalcin, two typical biomarkers that can simulate bone maturation, were augmented following implantation of chitosan nanofiber scaffolds. Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline phosphatase and osteocalcin gene expressions. Our results suggest the potential of chitosan nanofiber scaffolds for therapy of bone diseases, including bone defects and bone fractures.

No MeSH data available.


Related in: MedlinePlus