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Three-dimensional quantitative micromorphology of pre- and post-implanted engineered heart valve tissues
Chad E Eckert1, Brandon T Mikulis, Danielle Gottlieb
1Department of Bioengineering, Swanson School of Engineering, McGowan Institute for Regenerative Medicine, University of Pittsburgh, 300 Technology Drive, Suite 300, Pittsburgh, PA 15219, USA.
Annals of Biomedical Engineering
|September 21, 2010
Summary
This study reveals significant changes in the scaffold structure of engineered heart valve tissue (EHVT) after implantation. The scaffold fragments over time, integrating into a new collagenous matrix, offering insights for tissue engineering.
Area of Science:
- Biomaterials Science and Tissue Engineering
- Cardiovascular Research
- Regenerative Medicine
Background:
- A knowledge gap exists in understanding the three-dimensional (3D) formation and remodeling of engineered heart valve tissue (EHVT) from in vitro culture to in vivo function.
- Detailed microstructural analysis of EHVT during its development and integration is crucial for improving tissue-engineered heart valve therapies.
Purpose of the Study:
- To investigate the 3D microstructural changes of EHVT, specifically the scaffold and collagen matrix, from pre-implantation (PRI) to post-implantation (POI) at 12 weeks.
- To quantify scaffold fiber architecture and collagen density over time in vivo.
- To guide future 2D histological studies by assessing the impact of sectioning spacing on data fidelity.
Main Methods:
- Employed a novel serial confocal microscopy technique to capture 3D microstructural data of EHVT.
- Developed custom software for quantifying scaffold fiber features (length, tortuosity, separation, orientation) using a 3D fabric tensor.
- Analyzed collagen and cellular density, comparing PRI and POI specimens, and evaluated data fidelity with varying sectioning intervals.
Main Results:
- The polyglycolic acid (PGA): poly(L-lactide) (PLLA) scaffold, initially forming an oriented network, fragmented significantly by 12 weeks post-implantation (volume fraction decreased from 7.79% to 2.03%).
- The fragmented scaffold formed a randomly distributed network within a dense, contiguous collagenous matrix in POI specimens.
- Collagen density remained similar between PRI and POI, with slightly more homogenous transmural distribution in POI. Sectioning up to 25 µm for scaffold morphology and 50 µm for collagen density preserved information fidelity.
Conclusions:
- This study provides the first high-resolution, large-volume investigation of in vivo EHVT microstructure evolution.
- Significant scaffold degradation and remodeling into a collagenous matrix occur within 12 weeks of implantation.
- The observed morphological changes are critical for developing advanced constitutive models to understand EHVT formation and remodeling, informing future tissue engineering strategies.
