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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

Control 40% (A, C) and 50% (B, D) defects three months post-operation.(A, B), whole mounts stained with methylene blue/alizarin red. C, D, H & E-stained sections. No regeneration has taken place. In the sections, muscle and connective tissue have filled the defect space (arrows). T = tibia. Bars = 400 μm.
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pone.0130819.g004: Control 40% (A, C) and 50% (B, D) defects three months post-operation.(A, B), whole mounts stained with methylene blue/alizarin red. C, D, H & E-stained sections. No regeneration has taken place. In the sections, muscle and connective tissue have filled the defect space (arrows). T = tibia. Bars = 400 μm.

Mentions: None of the untreated 40% and 50% defects showed any regeneration by three months post-operation, or even at 5–6 months. X-ray and CT scans were negative at all time points. MB/AR staining and sections stained with H&E showed clearly that at three months post-operation the cut ends of the fibula had capped off without further regeneration and that the defects were filled with disorganized fibrous connective tissue and regenerated muscle (Fig 4). Using a definition of CSD as the smallest size defect that did not regenerate over the course of our experiments (up to six months), these data indicate that the CSD for the axolotl fibula is greater than 20%, but less than 40%.


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)

Control 40% (A, C) and 50% (B, D) defects three months post-operation.(A, B), whole mounts stained with methylene blue/alizarin red. C, D, H & E-stained sections. No regeneration has taken place. In the sections, muscle and connective tissue have filled the defect space (arrows). T = tibia. Bars = 400 μm.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130819.g004: Control 40% (A, C) and 50% (B, D) defects three months post-operation.(A, B), whole mounts stained with methylene blue/alizarin red. C, D, H & E-stained sections. No regeneration has taken place. In the sections, muscle and connective tissue have filled the defect space (arrows). T = tibia. Bars = 400 μm.
Mentions: None of the untreated 40% and 50% defects showed any regeneration by three months post-operation, or even at 5–6 months. X-ray and CT scans were negative at all time points. MB/AR staining and sections stained with H&E showed clearly that at three months post-operation the cut ends of the fibula had capped off without further regeneration and that the defects were filled with disorganized fibrous connective tissue and regenerated muscle (Fig 4). Using a definition of CSD as the smallest size defect that did not regenerate over the course of our experiments (up to six months), these data indicate that the CSD for the axolotl fibula is greater than 20%, but less than 40%.

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