20.109(S10):Notebook/T/R Blue Research Proposal/2010/04/25: Difference between revisions

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==(Tentative) Project Idea and Overview==
==(Tentative) Project Idea and Overview==
Regeneration or repair of myocardial tissue by pulse vibrations.
Regeneration or repair of myocardial tissue by pulse vibrations using conditions previously shown to be conducive to skin wound healing.
Goals:
 
* reduce natural scarring of damaged tissue
'''OVERALL GOAL''':
* perform ''in vitro'' studies on cardiac tissue, combining physiologically-relevant mechanical stimuli with presence of certain growth factors that have been shown to have a positive effect on healing (minimal scarring)
We would like to find if mechanical manipulation (with exact parameter values, if we're successful) is capable of reduce natural scarring of damaged myocardial tissue so as to rescure normal function and not impede natural mechanical and electrical properties of the tissue.


==Background==
==Background==

Revision as of 08:47, 27 April 2010

Pei and Leanna's Research Proposal <html><img src="/images/9/94/Report.png" border="0" /></html> Main project page

Topic

Tissue Engineering and Regenerative Medicine using physiologically-relevant mechanical stimuli

(Tentative) Project Idea and Overview

Regeneration or repair of myocardial tissue by pulse vibrations using conditions previously shown to be conducive to skin wound healing.

OVERALL GOAL: We would like to find if mechanical manipulation (with exact parameter values, if we're successful) is capable of reduce natural scarring of damaged myocardial tissue so as to rescure normal function and not impede natural mechanical and electrical properties of the tissue.

Background

Improved success with repair and regeneration of vocal fold tissue, bone tissue, and even teeth has been accomplished through physiologically-relevant mechanical stimulation.

References

  • need references of previous attempts (by varying methods) to repair/regenerate cardiac tissue (reference number 1 is basically what we're basing our experimental plan off of)

1. Palatinus JA, Rhett JM, Gourdie RG. Translational lessons from scarless healing of cutaneous wounds and regenerative repair of the myocardium. J Mol Cell Cardio. 2010;48:550-557.

In mammals, the healing response to a wound is scarring; a result of fibroblast proliferation and scar tissue. While this provides a partial restoration of the structure and function of the original tissue, this can generally lead to further harm to the tissue, especially in the heart.

When the heart encounters trauma, it is forced to heal while maintaining function. The heart, relative to other tissues, heals with profound fibrosis and scarring with minimal regeneration. Healing consists of three phases: inflammation, proliferation, and maturation. Inflammation: neutrophil accumulation, macrophage and monocyte infiltration. Proliferation: propogation of cells that have migrated to the wound (epithelial, fibroblasts, endothelial). Maturation: remodeling of collagen to form a scar.

Following myocardial infarction (MI), the most common post-MI cause of death is ventricular arrhythmia. Revascularization of the wound area is of utmost importance, although in some areas of the tissue, neovasculariztion could lead to complications. Growth factors that demonstrate potential in preclinical studes (ex: VEGF-A, FGF-2, PDGF) have yielded disappointling clinical results. TGF-beta is known to reduce scarring, and may even be good for the heart, so this is a possibility in further study. Modulation of the collagen in the scar is another area that needs further study, but would probably help in cardiovascular healing. Little is known about the fibrocyte, but some reports indicate that these cells improve the healing process. The zebrafish is known for its ability to regenerate tissues including the cardiac muscle. The human heart is more susceptible to arrhythmias than newt or fish hearts, however. The MRL mouse has the ability to scarlessly heal ear punch wounds, but too similarly to wt and not in the heart tissue. Diabetics also show a different response to injury.
  • need references of other types of tissue repair by mechanical stimulation or signaling

2. Kutty JK, Webb K. Vibration stimulates vocal mucosa-like matrix expression by hydrogel-encapsulated fibroblasts. J Tissue Eng Regen Med. 2009;4:62-72.

This study investigated the effect of vibratory stimulation on ECM gene expression and synthesis by fibroblasts encapsulated within hyaluronic acid hydrogels that approximate the viscoelastic properties of vocal mucosa. The objective was to find a method for reducing vocal scarring, restoring native matrix composition and improving vocal quality in the event of injury to the vocal fold ECM. Results indicated that vibration is a critical epigenetic factor that regulates vocal fold ECM, and that rapid restoration of the phonatory microenvironment may achieve the stated objective.


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