Microribbon-based hydrogels for cartilage regeneration : a LEGO®-building approach
Abstract/Contents
- Abstract
- Articular cartilage (AC) is the smooth tissue that lines the ends of joints and enables painless, frictionless movement. Damage to AC occurs quite frequently, and due to the avascular nature of cartilage, AC will not intrinsically heal once damaged. Often, AC damage progresses into osteoarthritis, a debilitating disease that currently affects 30 M Americans and costs the US healthcare > $185B annually. Current treatments for articular cartilage defects create mechanically inferior tissue that fails in the joint environment. Cartilage tissue engineering (CTE) aims to recreate articular cartilage with correct structure and function to replace damaged cartilage and thus, prevent the progression to osteoarthritis. Mesenchymal stem cells (MSCs) are an attractive cell source for cartilage tissue engineering as they are easily harvested, abundant, and can differentiate into chondrocytes. Hydrogels are 3D polymeric networks that are often used for CTE due to their tissue-like water content, injectability, biocompatibility, tunability, and ability to homogenously encapsulate cells. However, conventional hydrogels are nanoporous, which physically restrict encapsulated cells, leading to slow and pericellular ECM deposition in the neocartilage. This lack of robust ECM deposition results in cartilage with low compressive moduli, even after many weeks of culture. Additionally, these hydrogels are weak in structural integrity and fracture during cyclic loading, a physiologic process that cartilage must withstand during locomotion. Furthermore, most hydrogel attempts to date create homogenous cartilage tissue, which fail to mimic the structural and compositional zonal heterogeneity in AC necessary for proper function. And finally, previously demonstrated robust MSC chondrogenic differentiation required soluble factors to be supplemented to the media for many weeks. For clinical translation, incorporating drug delivery into the scaffold would decrease the needed in vitro culture period and decrease the time to patient treatment. Our lab recently developed microribbon (μRB) hydrogels that are shock-absorbing and accelerate neocartilage deposition by MSCs compared to conventional hydrogels. However, the compressive property of the produced neocartilage was subphysiologic, the tissue was homogenous, and tissue formation required soluble factor delivery during media exchange. This thesis work focused on: expanding the μRB toolbox to create neocartilage with zonal organization and mechanical properties on par with native cartilage, fundamentally understanding how MSCs sense the μRB platform, and creating a drug delivery system that is compatible with the μRB system and useful for in vivo MSC differentiation. Specifically, the following aims were completed in this thesis: Aim 1. Synthesize μRBs with tunable compositions for forming 3D macroporous stem cell niche and evaluate the effects of varying μRB composition on enhancing MSC-based cartilage formation in 3D. Aim 2. Examine the effects of ROCK inhibition on MSC chondrogenesis in μRB scaffolds and compare the response to other conventional culture models. Aim 3. Develop spatially patterned μRB scaffolds to guide zonal-specific differentiation of MSCs and regenerate articular cartilage with biomimetic zonal organization. Aim 4. Validate the potential of nanoparticle-containing μRB scaffolds with controlled release of growth factor for guiding MSC-based cartilage regeneration in vivo. This thesis demonstrates that the μRB-based platform offers a modular, building block approach to robust and successful cartilage tissue engineering.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Gegg, Courtney Alison |
|---|---|
| Degree supervisor | Yang, Fan, (Bioengineering researcher and teacher) |
| Thesis advisor | Yang, Fan, (Bioengineering researcher and teacher) |
| Thesis advisor | Bhutani, Nidhi |
| Thesis advisor | Smith, R. A, (Geologist) |
| Degree committee member | Bhutani, Nidhi |
| Degree committee member | Smith, R. A, (Geologist) |
| Associated with | Stanford University, Department of Bioengineering. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Courtney Gegg. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Courtney Alison Gegg
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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