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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

Left, MB-stained whole mount of 50% defect treated with BMP4/HGF, 3 months post-operation.A short cone of cartilage (arrow) regenerated from the proximal end of the fibula. No regeneration took place from the distal end. Right, MB-stained whole mount of 50% defect treated with BMP4/HGF in which short cones of cartilage regenerated from both the proximal and distal ends of the fibula (arrows). Both specimens illustrate a common phenomenon encountered after removal of 50% of the bone, namely that the remaining distal and/or proximal bone segments regress to create closer to a 70% gap.
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pone.0130819.g010: Left, MB-stained whole mount of 50% defect treated with BMP4/HGF, 3 months post-operation.A short cone of cartilage (arrow) regenerated from the proximal end of the fibula. No regeneration took place from the distal end. Right, MB-stained whole mount of 50% defect treated with BMP4/HGF in which short cones of cartilage regenerated from both the proximal and distal ends of the fibula (arrows). Both specimens illustrate a common phenomenon encountered after removal of 50% of the bone, namely that the remaining distal and/or proximal bone segments regress to create closer to a 70% gap.

Mentions: The BMP-4/HGF combination yielded two cases of partial regeneration (Fig 10) and four cases of extensive regeneration out of 20 limbs (Figs 11 and 12). The case illustrated in Fig 11 shows that regeneration of new cartilage surrounded by a shell of bone took place over the length of the gap. The regenerated skeletal tissue was not within the gap, however, but was attached to the side of the tibia, suggesting that its origin was the periosteum of the tibia. Fig 12 shows a case where cartilage regenerated across half the defect from the proximal end of the fibula.


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)

Left, MB-stained whole mount of 50% defect treated with BMP4/HGF, 3 months post-operation.A short cone of cartilage (arrow) regenerated from the proximal end of the fibula. No regeneration took place from the distal end. Right, MB-stained whole mount of 50% defect treated with BMP4/HGF in which short cones of cartilage regenerated from both the proximal and distal ends of the fibula (arrows). Both specimens illustrate a common phenomenon encountered after removal of 50% of the bone, namely that the remaining distal and/or proximal bone segments regress to create closer to a 70% gap.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130819.g010: Left, MB-stained whole mount of 50% defect treated with BMP4/HGF, 3 months post-operation.A short cone of cartilage (arrow) regenerated from the proximal end of the fibula. No regeneration took place from the distal end. Right, MB-stained whole mount of 50% defect treated with BMP4/HGF in which short cones of cartilage regenerated from both the proximal and distal ends of the fibula (arrows). Both specimens illustrate a common phenomenon encountered after removal of 50% of the bone, namely that the remaining distal and/or proximal bone segments regress to create closer to a 70% gap.
Mentions: The BMP-4/HGF combination yielded two cases of partial regeneration (Fig 10) and four cases of extensive regeneration out of 20 limbs (Figs 11 and 12). The case illustrated in Fig 11 shows that regeneration of new cartilage surrounded by a shell of bone took place over the length of the gap. The regenerated skeletal tissue was not within the gap, however, but was attached to the side of the tibia, suggesting that its origin was the periosteum of the tibia. Fig 12 shows a case where cartilage regenerated across half the defect from the proximal end of the fibula.

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