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Resolving differential vascular graft remodeling using longitudinal multiphoton tracking in a 3D culture platform
David R Maestas1, Trin Murphy1, Katarina M Martinet1
1Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
Biorxiv : the Preprint Server for Biology
|March 23, 2026
Summary
This study introduces a novel organotypic culture system for evaluating tissue-engineered vascular grafts (TEVGs). The platform enables longitudinal assessment of vascular graft remodeling, reducing the need for extensive in vivo implantation studies.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Vascular Biology
Background:
- Tissue-engineered vascular grafts (TEVGs) offer alternatives for vascular replacement but require extensive implantation studies.
- Current models obscure long-term microscale remodeling processes crucial for graft outcomes.
Purpose of the Study:
- To develop an organotypic culture platform for longitudinal assessment of TEVG remodeling.
- To provide a pre-clinical tool for evaluating biomaterial scaffold designs.
Main Methods:
- Coupling rat aortic explants with acellular grafts in a cylindrical organotypic culture.
- Utilizing label-free multiphoton imaging (SHG and 2PEF) for longitudinal collagen and cellular analysis.
- Assessing platform sensitivity with TGF-β isoform treatments and correlating with gene expression.
Main Results:
- The platform successfully visualized evolving collagen architecture in TEVGs.
- Compatibility with various biomaterials, fluorescent reporters, and assays was confirmed.
- Observed architectural fiber distributions in culture matched 6-month aortic explant data, validating the remodeling readout.
Conclusions:
- The developed organotypic culture platform enables accessible, longitudinal assessment of TEVG remodeling.
- This system serves as a valuable decision-informing tool for biomaterial scaffold selection prior to surgical implantation.
- It offers a promising alternative to resource-intensive implantation studies for TEVG development.
