Date of Award
8-2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Bioengineering
Committee Chair/Advisor
Dr. Jeremy Mercuri
Committee Member
Dr. Delphine Dean
Committee Member
Dr. Tong Ye
Committee Member
Dr. Douglas Wyland
Abstract
Focal Chondral Defects (FCDs) are cartilage injuries that affect about 900,000 Americans every year. Left untreated, these may lead to osteoarthritis and eventually necessitate painful knee replacements. Current treatment options are limited in terms of durability, cost, and availability of grafts. Tissue engineering, using natural scaffolds, are a highly attractive alternative promising cost efficiency, abundance, and long-term benefits. However, their low mechanical strength and dense matrices are impediments that could lead to sub-optimal repair.
In this work, a natural biomaterial, the bovine nucleus pulposus (bNP), derived from intervertebral disc tissue, was identified as a candidate scaffold for cartilage regeneration. Mechanical fortification and laser-drilling protocols that could triple bNP moduli and provide pathways for cellular infiltration respectively were developed. Afterwards, a novel decellularization strategy was formulated that reduced bovine DNA content to acceptable levels (/mg dry wt.), maintained sulfated glycosaminoglycan (sGAG) content within range of human cartilage (72 µg/mg dry wt) and resulted in a modulus that was considered conducive for bone marrow stem cell chondrogenesis (10-15 kPa). The resulting material, the Cartilage Analog (CA) was found to be cytocompatible (over 14 days) and permissive of cellular infiltration.
In vitro analysis of the CA in chondrogenic media showed good cell attachment, long-term cytocompatibility (28 days), production of new cartilaginous matrix (73 µg/mg dry wt of sGAG) and a biochemical profile (sGAG:HydroxyProline = 1.32) that closely mimicked human hyaline cartilage (1.3). However, there was also observed a lower-then-expected aggregate modulus as well as a shrinkage of the scaffold due to cell-mediated contractions. Nevertheless, these findings do indicate that the CA indeed holds potential as a biomaterial that could regenerate articular cartilage. As such, it could be used in bone marrow stimulation procedures for the treatment of FCDs. Future work would involve in vivo evaluations of the CA in both subcutaneous and orthotopic locations.
Recommended Citation
Thomas, Vishal, "The Development of a Novel Cartilage Analog Scaffold for Chondral Regeneration" (2024). All Dissertations. 3726.
https://open.clemson.edu/all_dissertations/3726
Author ORCID Identifier
0000-0003-0351-4392