BIOMED PhD Thesis Defense

Title:
Regulatory Roles of Fibril-Forming Collagens in Cartilaginous Tissue Biomechanics and Mechanobiology
 
Speaker:
Chao Wang, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
 
Advisor:
Lin Han, PhD
Associate Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University

Details:
In the knee joint, articular cartilage and meniscus work synergistically to enable our daily activities such as walking, running and jumping. Although the importance of maintaining the health of both tissues cannot be emphasized more and the injury prevalence of both tissues are common, the state of William Hunter in 1743 that “once it destroyed, it never repairs” still holds true after three centuries. This can be attributed to both tissues’ poor capability of intrinsic repair due to their characteristics of non/low vascularity, innervation and very low cellular mitotic activity. Furthermore, despite decades of progresses in tissue engineering, successful regeneration of both tissues remains elusive. This is, at least partly, due to lacking a comprehensive understanding of the molecular activities that govern the assembly of the complex hierarchical matrix architecture, in turn, the reciprocal interactions between the matrix and residing cells.

To address these limitations, a far-reaching knowledge of the roles of fibril-forming collagen, a key component in the extracellular matrix of both articular cartilage and meniscus, could serve as an indispensable foundation to better understand the tissue function. Therefore, first part of this dissertation defense is to elucidate the role of type III collagen in regulating the morphology, nanostructure and biomechanical properties of both articular cartilage and meniscus by studying the phenotypic changes in type III collagen haploinsufficiency mice. Second portion is to elucidate the nanomechanics and micromechanobiological role of the pericellular matrix (PCM), the immediate microniche of residing cells, in fibrocartilage. We queried the roles of proteoglycan and type V collagen in the regulating the structural integrity, matrix assembly and intracellular calcium signaling of murine meniscus. Our findings, for the first time, uncovered the structural and mechanical role of two regulatory collagens, type III and V, in cartilaginous tissues matrices, providing better clinical comprehension to Ehlers-Danlos syndrome (EDS), a rare human genetic disease caused by collagen gene mutations. We also defined the unique molecular and functional properties of the PCM in fibrocartilage, providing a path for enhancing fibrocartilage regeneration by modulating the PCM-mediated cell mechanotransduction.

The School of Biomedical Engineering, Science and Health Systems is proud to host the 2023 Northeast Bioengineering Conference (NEBEC 2023)

ABSTRACT SUBMISSION AND CONFERENCE REGISTRATION ARE NOW OPEN!

⬆️ Register here: nebec.org

Scientific Sessions:
 We welcome contributions from all areas of Biomedical Engineering.

* Cellular and Molecular Bioengineering
* Biomechanics
* Tissue Engineering
* Synthetic Biology
* Computational Biology/Bioinformatics
* Medical Devices
* Biophotonics / Biomedical Imaging

The overarching objective of the NEBEC conference is to stimulate collaboration and promote biomedical engineering research and education programs in the Northeast United States.

BIOMED PhD Research Proposal

Title:
Modulating Macrophage Response to Biomaterials by Leveraging Biotin-Avidin Interactions

Speaker:
Victoria Nash, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Advisor:
Kara Spiller, PhD
Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University

Details:
Tissue regeneration is a complex series of events, driven by highly plastic immune cells: macrophages. Typically, “pro-inflammatory” macrophages act early to support angiogenesis, while later acting “pro-reparative” macrophages support newly sprouted vasculature, assisting in tissue repair. This temporal switch is crucial to prevent either chronic inflammation or fibrosis. Approaches used in biomaterials engineering to temporally influence macrophage phenotype are surface coating or encapsulation of cytokines, however these are not amenable to a variety of biomaterials. Affinity interactions, such as heparin or albumin have been leveraged for drug delivery. They rely on weak interactions, like hydrogen bonding, to retain and deliver the drug. However, these systems require specific biomaterial formulations to 1) incorporate heparin or albumin into the material and 2) provide a favorable environment for weak interactions to occur between the drug and biomaterial for drug delivery. While these systems work for small molecules and some amino acids, they are limited for cytokine delivery because weak interactions are not stable enough for effective delivery.

Biotin-avidin affinity becomes a favorable option because biotin, avidin (or its variants), can be directly conjugated to proteins, biomaterials, and even cells, without altering its bioactivity. Historically, avidin was first used as a model adjuvant, then explored as a protein carrier for adjuvants in vaccines, but modern uses of the affinity pair, biotin-avidin, range from analytical assays to targeted radioimmunotherapy. Biotin-avidin interactions are rarely used for drug release, due to biotin’s low dissociation rate from avidin (Kd = 10-15 M). However, release can be triggered by introducing free biotin to the system, promoting the release of biotinylated molecules from avidin. Yet it is not known how bioconjugation parameters can affect biotin-avidin interactions, potentially leading to controlled release profiles. Or even how biotin or avidin influence macrophage phenotype in the absence of additional cytokines. Therefore, the goal of this study is to determine how bioconjugation parameters can control biotin-avidin interactions to release a biotinylated cytokine to modulate macrophage phenotype in response to biomaterials.