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Regenerative Medicine for Battlefield Injuries

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Annual rept. 19 Sep 2012-18 Sep 2013

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The purpose of this research is to identify the optimum combination of growth factors that stimulate cartilage regeneration across a critical size defect CSD in the fibula, using the axolotl, Abystoma mexicanum as a model system. The scope of the research is to characterize combinations of soluble factors growth factors and tissue extracts absorbed into a standard scaffold of pig small intestine submucosa SIS. From October 2011 to April 2012, we determined the CSD as slightly less than 40 the length of the fibula fracture, characterized the response to fracture and defects of various sizes, and identified 7 growth factors involved in fracture repair by bioinformatic analysis. We determined that regeneration takes place over gaps of up to 20, but not at 40 and 50 and that SIS scaffold alone does not promote regeneration. In April 2013 we presented a poster summarizing this data at the Experimental Biology meeting in Boston. Since then, we have been testing the ability of a number of growth factor combinations, blastema extract, and limb tissue extract to promote cartilage regeneration across 50 gaps 20 greater than the actual CSD. Three sets of factors promoted such regeneration by 3 months postimplant, the growth factor combinations BMP4VEGF and BMP4HGF, and protein extract of intact limb tissue, of which the latter two gave the best results. We determined that the best way to image the regenerating tissue was by whole mount methylene blue staining and routine HE histology, reserving micro- CT imaging for bone only. We think BMP4HGF and tissue extract were successful because they initiated the whole cascade of events required for cartilage development. These results indicate that the axolotl fibula can be used as an in vivo screening system for soluble factors as well as scaffolds that promote cartilage regeneration across a CSD.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

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