BME PhD Prospectus Defense - Yifan Peng
- Starts: 9:00 am on Thursday, October 3, 2024
Title: "Characterization of a Novel Latent TGF-β Scaffold to Improve Neocartilage Regeneration"
Advisory Committee: Michael Smith, PhD – BU BME (Chair) Michael Albro, PhD – BU ME (Advisor) Brianne Connizzo, PhD – BU BME Matthew Layne, PhD - BU Biochemistry & Cell Biology
Abstract: Osteoarthritis (OA) is a painful and debilitating disease affecting over 500 million individuals worldwide, leading to loss of life quality but in lack of effective treatment. Cartilage tissue engineering is a promising OA treatment strategy whereby cell-seeded scaffolds are cultivated to generate neocartilage repair tissues. The long-term survival of neocartilage is dependent on its ability to recapitulate the complex spatial distribution of the composition, structure, and material properties of native hyaline cartilage, which are necessary for load-bearing functionality. Transforming growth factor beta (TGF-β) has emerged as one of the most prominent mediators of cartilage regeneration due to its capability to enhance chondrogenesis and accelerate ECM biosynthesis. While metabolic stimulation is necessary for accelerating ECM biosynthesis during in vitro development, it may compromise the tissue’s ability to survive post-implantation in the nutrient-deficient synovial joint environment. As illustrated for conventional culture protocols, metabolic stimulation via active TGF-β produces neocartilage with native- matched functional mechanical properties, but leads to hypermetabolism, marked by elevated glucose consumption rates, which are predicted to hinder glucose delivery to tissues after implantation. Recently, we developed a novel scaffold platform where TGFβ is delivered to embedded chondrocytes in its native latent form (LTGF-β). Chondrocytes activate scaffoldconjugated LTGF-β, giving rise to moderated, physiologic TGF-β activity levels (0.1-0.7 ng/mL in situ activity levels), akin to those present during native cartilage development. In prior work, we showed that LTGF-β scaffolds provide more optimal tissue development, marked by neocartilage with native-matched mechanical properties, while maintaining a more hyaline-cartilage-like morphology and composition relative to neocartilage produced from active TGF-β. In the current study, I explore 3 unique aims to further explore how physiologic TGF-β activity levels promoted by LTGF-β scaffolds can yield neocartilage with native-matched properties to survive in the native mechanical environment while further beneficially maintaining lower metabolic rates of construct-seeded chondrocytes, which allows neocartilage to survive in the nutrientdeficient synovial joint environment.
- Location:
- 8 St. Marys St. PHO 901