Progress 10/20/15 to 02/02/17
Outputs
Target Audience:Veterinarian surgeons, biological engineers. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Two doctoral students, Bryn Brazile, Katherine Copeland, have participated in this project. There are also five undergraduate students and one veterinary student participating in the animal experiment. How have the results been disseminated to communities of interest?Our project has generated four conference presentation, two journal papers, and one book chapter. What do you plan to do during the next reporting period to accomplish the goals?We will further assess the regenerative properties of the neonatal heart ECM using porcine as a model. The goal is to understand the regenerative potential of fetal heart ECM and its interaction with cells.
Impacts
What was accomplished under these goals?
Our research in 2016 has been focusing on the heart's regenerative potential in right after birth. Previous studies have shown that neonatal mice could regenerate their hearts after partial resection until day 7 after birth via cardiomyocyte proliferation. The majority of the new cardiomyocytes had originated from preexisting cardiomyocytes as indicated by genetic fate mapping. However, there have been other reports that suggest the complete regenerative potential of neonatal mouse hearts is limited on account of reduced cardiomyocyte potential and that the mouse hearts healed by scar formation instead. In this study, we take a major further step and look to determine if this phenomenon exists in mammals which warrants a more in-depth investigation. We are very curious whether or not the full regenerative potential of the neonatal heart exists in large mammals, with a goal to eventually harness this potential for clinical applications. To determine the regenerative potential of the neonatal pig hearts, we subjected the neonatal piglets to an apex resection surgery, in which 30% thickness of the left ventricle wall was removed. Heart muscle function was assessed via transthoracic echocardiograms, and gross anatomical assessment was performed upon necropsy of each piglet. By using a pig model, we have taken the challenge and successfully performed a study to investigate the transient regenerative potential of the neonatal hearts in large mammals. The partial apex resection was performed on 0 day old and 7 day old neonatal piglets. The sham group, in which an open chest procedure was performed without introducing partial apex resection, was used as the controls for both 0 day and 7 day groups. The animal experiments were very successful with strong support from the College of Veterinary Medicine with Dr. Ryan Butler as the leading surgeon. During surgery, it was noted that the 0 day old hearts were more pliable, and the partial apex resection could be more easily performed than the 7 day old hearts, which had a more rigid tissue structure. All piglets responded to the surgery well, recovered soon, and lived normally with the mother pig until euthanasia at 4 weeks post-surgery. The echocardiogram measurements indicated a significant decrease in fractional shortening and ejectile function for the 7 day old apex resection group at the 4 week post-surgery time point, thus likely indicating possible scar formation or unrecoverable damage to the heart wall. Upon gross necropsy, the 0 day old group showed no sign of scarring or any indication of the induced injury; of the 7 day old group, only 1 piglet had visual signs of possible scarring in the apex region by morphological observation. In our histological study, the 0 day old piglets show promise that the piglets can better recover from an apex resection of the heart wall. The transient regenerative potential is likely due to the size of the resected heart tissue, since the piglets in the 0 day surgery group with the smallest resected piece of tissue seemed to fully recover. The actively dividing and differentiating cells, shown in the 0 day piglet that died prematurely, suggest there are factors that are promoting heart muscle regeneration. This very important observation warrants further investigation of the 0 day old apex resection group, especially in the days to one week after the apex resection to determine how the cells, biofactors, and ECMs are promoting the cell and tissue regeneration. By determining the underlying mechanism of heart regeneration during the neonatal stage, we can harness the biological and biomechanical cues that trigger full heart muscle regeneration, and thus design novel therapeutic approaches to assist heart regeneration in MI patients.
Publications
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Xiaodan Shi, Song Zhang, Katherine Copeland, Yue Liu, Huajian Gao, Jun Liao. Topological and geometrical analysis of 3D epicardial elastin fiber network. Biomedical Engineering Society Annual Meeting, Minneapolis, Minnesota, October 5-8, 2016
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Sarah Fitzgerald, Sammira Rais-Rohani, Heath Baskin, Richard Summers, Robert Hester, and Jun Liao. Biomechanics of the Porcine Optic Nerve. Biomedical Engineering Society Annual Meeting, Minneapolis, Minnesota, October 5-8, 2016
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Sallie Lin, Bryn Brazile, Katherine Copeland, Heath Baskin, and Jun Liao. Viscoelastic Properties of Tricuspid Valve Leaflets. Biomedical Engineering Society Annual Meeting, Minneapolis, Minnesota, October 5-8, 2016
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Xiaodan Shi, Bryn Brazile, Sourav Patnaik, Jim Cooley, Raj Prabhu, Lakiesha Williams, Song Zhang, Jun Liao. Elastin Fiber Network in Porcine Epicardium: 3D Visualization and Quantification. Summer Biomechanics, Bioengineering, and Biotransport Conference. National Harbor, Maryland, June 29-July 2, 2016
- Type:
Book Chapters
Status:
Published
Year Published:
2016
Citation:
Bryn Brazile, Sallie Lin, Katherine M. Copeland, J. Ryan Butler, Jianjun Guan, and Jun Liao. Chapter 6: Ultrastructure and Biomechanical Properties of the Skeletal Muscle ECM: Implications in Tissue Regeneration. Bio-Instructive Scaffolds for Musculoskeletal Tissue Engineering and Regenerative Medicine. Editors: Justin L. Brown, Sangamesh G. Kumbar, Brittany L. Banik, Elsevier, Page: 139-160, 2016
- Type:
Journal Articles
Status:
Published
Year Published:
2016
Citation:
Bo Wang, Sourav S. Patnaik, Bryn Brazile, J. Ryan Butler, Andrew Claude, Ge Zhang, Jianjun Guan, Yi Hong, and Jun Liao. Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs. Critical Review in Biomedical Engineering. 43(5-6): 455-471, 2016
- Type:
Journal Articles
Status:
Published
Year Published:
2016
Citation:
Mazin S Sirry, J Ryan Butler, Sourav S Patnaik, Bryn Brazile, Robbin Bertucci, Andrew Claude, Ron McLaughlin, Neil H Davies, Jun Liao, Thomas Franz. Characterization of the mechanical properties of infarcted myocardium in the rat under biaxial tension and uniaxial compression. Journal of the Mechanical Behavior of Biomedical Materials. 63: 252-264, 2016
|