Scaffolds that Mimic Proximal Tubule’s Physical and Biological Characteristics
Board Location: #118
Discipline: Technology and Engineering
Subcategory: biomedical
Session: 3
Kyra Ramirez - Alabama State University
Co-Author(s): Amrita Natarajan, Alabama State University, Montgomery, Alabama; Anjali Sudha, Alabama State University, Montgomery, Alabama; Dr. Derrick Dean, Alabama State University, Montgomery, Alabama.
Scaffolds that Mimic Proximal Tubule’s Physical and Biological Characteristics
Kyra A. Ramirez, Amrita Natarajan, Anjali Sudha and Dr. Derrick Dean
Biomedical Engineering
Alabama State University
Chronic kidney disease (CKD) is a very `prevalent problem, affecting nearly 37.5 million people in the US, and over 700 million people globally. The endpoint of CKD is typically renal fibrosis, characterized by an increase in extracellular matrix (ECM) deposition. Patients with CKD who reach end-stage renal disease are often placed on a dialysis therapy while waiting for a suitable donor kidney (usually from the United Network for Organ Sharing—or UNOS—list). However, kidney transplantation is limited by the insufficient number of available healthy donor kidneys, and patients’ time left to live is often shorter than their wait time on the UNOS list.
While renal injury can occur in many locations, the convoluted proximal tubule (PT) is the most frequently damaged site. The PT is responsible for roughly 65–80% of nutrient absorption and transport from the renal filtrate to the blood. Therefore, circulating drugs and their metabolites often accumulate in the PT at high concentrations in both intra- and intercellular space, which can cause damage. Tissue engineering has the potential to regenerate PT tissue which can serve as a therapy for patients with CKD. The hypothesis of this research is tissue scaffolds that mimic the architecture and composition of proximal tubules will be effective at regenerating tissue. Nanofibrous scaffolds were fabricated by electrospinning a solution of polyurethane (15% wt. in tetrahydrofuran). The morphology was characterized using scanning electron microscopy and tensile tests were performed to determine the mechanical properties. Renal epithelial cells were cultured on the scaffolds for 7 days. Fluorescence microscope images of the cells enabled imaging of their cytoskeleton on the luminal surface of the scaffolds. In conclusion, current studies have shown that the tubular structure of the scaffolds mimics the environment necessary for the successful proliferation of renal epithelial cells and may be able to serve as a functional proximal tubule with the ability to carry out absorption and transport processes. Future studies will focus on using confocal microscopy to image the epithelial cells in the lumen of the proximal tubules and study expression of the genetic markers organic anion transporters (OATs) and organic cation transporters (OCTs), which are two transporter genes that are involved in the absorption, distribution, and elimination of drugs, toxins, and other substances in the proximal tubules.
References: Rodrigues-Díez, R., Benedetti, V., Remuzzi, G. and Xinaris, C. (2017). Tissue Engineering of Renal Tissue (Kidney). In Tissue Engineering for Artificial Organs, A. Hasan (Ed.). https://doi.org/10.1002/9783527689934.ch18.
Peired, A.J., Mazzinghi, B., De Chiara, L., Guzzi, F., Lasagni, L., Romagnani, P. (2020) Bio
Funder Acknowledgement(s): We like to thank the funding source NSF CREST-2332041.
Faculty Advisor: Dr. Derrick Dean,
Role: Research assistant that constructed the electrospun tubule scaffolds.