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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

Preparation of electrospun chitosan nanofibers.Notes: Chitosan at 50 mg/mL (A), 60 mg/mL (B), 70 mg/mL (C), and 80 mg/mL (D) was separately dissolved in the electrospinning solutions and electrospun into different chitosan nanofibers. The surface morphologies of these electrospun chitosan nanofibers were observed and photographed using scanning electron microscopy at 5,000×.
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f2-ijn-10-5941: Preparation of electrospun chitosan nanofibers.Notes: Chitosan at 50 mg/mL (A), 60 mg/mL (B), 70 mg/mL (C), and 80 mg/mL (D) was separately dissolved in the electrospinning solutions and electrospun into different chitosan nanofibers. The surface morphologies of these electrospun chitosan nanofibers were observed and photographed using scanning electron microscopy at 5,000×.

Mentions: To prepare uniform chitosan nanofibers, various concentrations of chitosan were fed and tested (Figure 2). In this assay, the other operational parameters were fixed at an applied voltage of 17 kV, a tip-to-collector distance of 12 cm, a flow rate of 0.2 mL/h, and an ambient temperature of 32°C. When the feeding concentration of chitosan was 50 mg/mL, undesirable beads formed (Figure 2A). In comparison, the appearance of beads decreased at 60 mg/mL (Figure 2B). At a concentration of 70 mg/mL, continuous chitosan nanofibers were obtained, and beaded structures were limited (Figure 2C). In contrast, when the concentration of chitosan was as high as 80 mg/mL, uniform chitosan nanofibers were generated with no beads or aggregations, and their average diameter was approximately 200 nm (Figure 2D).


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)

Preparation of electrospun chitosan nanofibers.Notes: Chitosan at 50 mg/mL (A), 60 mg/mL (B), 70 mg/mL (C), and 80 mg/mL (D) was separately dissolved in the electrospinning solutions and electrospun into different chitosan nanofibers. The surface morphologies of these electrospun chitosan nanofibers were observed and photographed using scanning electron microscopy at 5,000×.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-10-5941: Preparation of electrospun chitosan nanofibers.Notes: Chitosan at 50 mg/mL (A), 60 mg/mL (B), 70 mg/mL (C), and 80 mg/mL (D) was separately dissolved in the electrospinning solutions and electrospun into different chitosan nanofibers. The surface morphologies of these electrospun chitosan nanofibers were observed and photographed using scanning electron microscopy at 5,000×.
Mentions: To prepare uniform chitosan nanofibers, various concentrations of chitosan were fed and tested (Figure 2). In this assay, the other operational parameters were fixed at an applied voltage of 17 kV, a tip-to-collector distance of 12 cm, a flow rate of 0.2 mL/h, and an ambient temperature of 32°C. When the feeding concentration of chitosan was 50 mg/mL, undesirable beads formed (Figure 2A). In comparison, the appearance of beads decreased at 60 mg/mL (Figure 2B). At a concentration of 70 mg/mL, continuous chitosan nanofibers were obtained, and beaded structures were limited (Figure 2C). In contrast, when the concentration of chitosan was as high as 80 mg/mL, uniform chitosan nanofibers were generated with no beads or aggregations, and their average diameter was approximately 200 nm (Figure 2D).

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