Description
TitleHyaluronic acid-based bioinks for cell-friendly bioprinting
Date Created2020
Other Date2020-01 (degree)
Extent1 online resource (xiv, 187 pages) : illustrations
DescriptionExtracellular matrix (ECM) is an intricate network of proteins, sugars, and proteoglycans that provides critical signaling context to resident cells through mechanical and bioactive properties. As such, the independent control of these features is a frequent target in the development of biomaterials. This research investigates the development of a bioink system based on thiol-modified hyaluronic acid (HA-S) and polyethylene glycol diacrylate (PEGDA) for 3D bioprinting. The objectives of this work were to (1) develop a versatile approach to independently control the mechanical and bioadhesive features of HAS-PEGDA across multiple time scales and (2) adapt the system to be amenable to 3D extrusion bioprinting.
To this end, we leveraged the distinct dual-crosslinking mechanism of HAS-PEGDA to control the mechanical properties at different time points. Rheological studies confirmed that two crosslinking reactions occur in HAS-PEGDA: (1) rapid crosslinking between HA-thiols and PEG-acrylates resulting in gelation in minutes and (2) prolonged disulfide crosslinking, which dramatically stiffens the network over a period of days-to-weeks. Like native HA, HAS-PEGDA does not support the adhesion of most healthy adult human cells, but the thiol modification provides a convenient target to introduce bioactive ligands. We demonstrated that the steady-state stiffness of the network can be manipulated independently of the initial crosslinking reaction by targeting a percentage of HA-thiols with peptide-ligands or inert spacers. Moreover, we identified ranges in which the mechanical and bioactive properties can be co-modulated in HAS-PEGDA, and we validated the biological functionality in vitro using human mesenchymal stem cells and rat dermal fibroblasts.
To adapt the formulation for 3D cell culture, reaction templates were developed to prioritize bioactive peptide-grafting, initial gelation, latent crosslinking, and network degradation, across time scales of seconds, minutes-to-hours, days, and weeks, respectively. Finally, we demonstrated that the time-dependent rheological features of HAS-PEGDA can be leveraged to formulate printable bioinks for extrusion-based 3D bioprinting. By harnessing the inherent viscoelastic features of HA, we identified a window of printing conditions that resulted in excellent cell viability, mechanical recovery, resolution, and bioink tunability. Taken together, the results presented in this thesis establish a customizable bioink system based on thiol-modified hyaluronic acid for extrusion-based bioprinting.
NotePh.D.
NoteIncludes bibliographical references
Genretheses, ETD doctoral
LanguageEnglish
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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