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The Axolotl Fibula as a Model for the Induction of Regeneration across Large Segment Defects in Long Bones of the Extremities.

Chen X, Song F, Jhamb D, Li J, Bottino MC, Palakal MJ, Stocum DL - PLoS ONE (2015)

Bottom Line: Fractures and defects of 10% and 20% of the total limb length regenerated well without any intervention, but 40% and 50% defects failed to regenerate after either simple removal of bone or implanting SIS scaffold alone.By contrast, scaffold soaked in the growth factor combination BMP-4/HGF or in protein extract of intact limb tissue promoted partial or extensive induction of cartilage and bone across 50% segment defects in 30%-33% of cases.These results show that BMP-4/HGF and intact tissue protein extract can promote the events required to induce cartilage and bone formation across a segment defect larger than critical size and that the long bones of axolotl limbs are an inexpensive model to screen soluble factors and natural and synthetic scaffolds for their efficacy in stimulating this process.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, School of Science, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States of America.

ABSTRACT
We tested the ability of the axolotl (Ambystoma mexicanum) fibula to regenerate across segment defects of different size in the absence of intervention or after implant of a unique 8-braid pig small intestine submucosa (SIS) scaffold, with or without incorporated growth factor combinations or tissue protein extract. Fractures and defects of 10% and 20% of the total limb length regenerated well without any intervention, but 40% and 50% defects failed to regenerate after either simple removal of bone or implanting SIS scaffold alone. By contrast, scaffold soaked in the growth factor combination BMP-4/HGF or in protein extract of intact limb tissue promoted partial or extensive induction of cartilage and bone across 50% segment defects in 30%-33% of cases. These results show that BMP-4/HGF and intact tissue protein extract can promote the events required to induce cartilage and bone formation across a segment defect larger than critical size and that the long bones of axolotl limbs are an inexpensive model to screen soluble factors and natural and synthetic scaffolds for their efficacy in stimulating this process.

No MeSH data available.


Related in: MedlinePlus

Bone volume fraction of regenerated bone in 10%- 50% defects at two months post-operation.The 20% defect is the same one illustrated in Fig 2. Top, red dashed lines show the cross-section level in the center of the 10% and 20% defects (A, B) and the 40% and 50% defects (C, D) where the measurements were taken. Both 10% and 20% defects regenerated a high volume fraction of bone, whereas there was much less regeneration in the 40% defects, and minimal regeneration in the 50% defects, which only regenerated at the cut ends of the fibula.
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pone.0130819.g005: Bone volume fraction of regenerated bone in 10%- 50% defects at two months post-operation.The 20% defect is the same one illustrated in Fig 2. Top, red dashed lines show the cross-section level in the center of the 10% and 20% defects (A, B) and the 40% and 50% defects (C, D) where the measurements were taken. Both 10% and 20% defects regenerated a high volume fraction of bone, whereas there was much less regeneration in the 40% defects, and minimal regeneration in the 50% defects, which only regenerated at the cut ends of the fibula.

Mentions: Fig 5 shows the newly regenerated bone volume fraction (BVF) in the middle of the regenerated region where bone density is expected to be least. In the 10% defects, the BVF was 74.4% and in the 20% defects it was 70.6%. The BVF for the 40% defects was 38.7%, and for the 50% defects, 11.3%. We used calcium-binding fluorochromes [35] to visualize sites of active mineralization in 10% vs. 50% defects in the fibula (Fig 6). In merged images of calcien (green) and alizarin complexone (red), regeneration of bone is clearly underway in the 10% defect by 3 weeks post-operation, as indicated by the separation of the green and red colors, whereas virtually no color separation had taken place at either end of the 50% gap.


The Axolotl Fibula as a Model for the Induction of Regeneration across Large Segment Defects in Long Bones of the Extremities.

Chen X, Song F, Jhamb D, Li J, Bottino MC, Palakal MJ, Stocum DL - PLoS ONE (2015)

Bone volume fraction of regenerated bone in 10%- 50% defects at two months post-operation.The 20% defect is the same one illustrated in Fig 2. Top, red dashed lines show the cross-section level in the center of the 10% and 20% defects (A, B) and the 40% and 50% defects (C, D) where the measurements were taken. Both 10% and 20% defects regenerated a high volume fraction of bone, whereas there was much less regeneration in the 40% defects, and minimal regeneration in the 50% defects, which only regenerated at the cut ends of the fibula.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476796&req=5

pone.0130819.g005: Bone volume fraction of regenerated bone in 10%- 50% defects at two months post-operation.The 20% defect is the same one illustrated in Fig 2. Top, red dashed lines show the cross-section level in the center of the 10% and 20% defects (A, B) and the 40% and 50% defects (C, D) where the measurements were taken. Both 10% and 20% defects regenerated a high volume fraction of bone, whereas there was much less regeneration in the 40% defects, and minimal regeneration in the 50% defects, which only regenerated at the cut ends of the fibula.
Mentions: Fig 5 shows the newly regenerated bone volume fraction (BVF) in the middle of the regenerated region where bone density is expected to be least. In the 10% defects, the BVF was 74.4% and in the 20% defects it was 70.6%. The BVF for the 40% defects was 38.7%, and for the 50% defects, 11.3%. We used calcium-binding fluorochromes [35] to visualize sites of active mineralization in 10% vs. 50% defects in the fibula (Fig 6). In merged images of calcien (green) and alizarin complexone (red), regeneration of bone is clearly underway in the 10% defect by 3 weeks post-operation, as indicated by the separation of the green and red colors, whereas virtually no color separation had taken place at either end of the 50% gap.

Bottom Line: Fractures and defects of 10% and 20% of the total limb length regenerated well without any intervention, but 40% and 50% defects failed to regenerate after either simple removal of bone or implanting SIS scaffold alone.By contrast, scaffold soaked in the growth factor combination BMP-4/HGF or in protein extract of intact limb tissue promoted partial or extensive induction of cartilage and bone across 50% segment defects in 30%-33% of cases.These results show that BMP-4/HGF and intact tissue protein extract can promote the events required to induce cartilage and bone formation across a segment defect larger than critical size and that the long bones of axolotl limbs are an inexpensive model to screen soluble factors and natural and synthetic scaffolds for their efficacy in stimulating this process.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, School of Science, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States of America.

ABSTRACT
We tested the ability of the axolotl (Ambystoma mexicanum) fibula to regenerate across segment defects of different size in the absence of intervention or after implant of a unique 8-braid pig small intestine submucosa (SIS) scaffold, with or without incorporated growth factor combinations or tissue protein extract. Fractures and defects of 10% and 20% of the total limb length regenerated well without any intervention, but 40% and 50% defects failed to regenerate after either simple removal of bone or implanting SIS scaffold alone. By contrast, scaffold soaked in the growth factor combination BMP-4/HGF or in protein extract of intact limb tissue promoted partial or extensive induction of cartilage and bone across 50% segment defects in 30%-33% of cases. These results show that BMP-4/HGF and intact tissue protein extract can promote the events required to induce cartilage and bone formation across a segment defect larger than critical size and that the long bones of axolotl limbs are an inexpensive model to screen soluble factors and natural and synthetic scaffolds for their efficacy in stimulating this process.

No MeSH data available.


Related in: MedlinePlus