Hydrogels for cartilage tissue engineering in mechanically relevant environments

Roberts, Justine Jenna

Graduate Thesis Or Dissertation

Hydrogels for cartilage tissue engineering in mechanically relevant environments Public Deposited

Analytics

Citations

Citeable URL: https://scholar.colorado.edu/concern/graduate_thesis_or_dissertations/b5644r755

Abstract

Tissue engineering offers the potential to replace cartilage that is damaged due to age, injury, or disease with a native equivalent produced by a chondrocyte (cartilage cell)-laden scaffold. Although joints are highly dynamic environments, scaffolds designed for articular cartilage tissue engineering are often developed in static environments. This raises questions as to whether they will translate to the highly dynamic mechanical environment found in vivo. In healthy joints, cartilage experiences maximum strains of 30% and frequencies from 0.1-2 Hz. This environment leads to the induction of fluid flow and dynamic cellular deformation, both of which can be sensed by chondrocytes through mechanotransduction. For a scaffold design to be successful, the loading environment should be considered. This thesis developed hydrogels to support tissue production and retain neocartilage under mechanically relevant compressive loading. Non-degradable and degradable poly(ethylene glycol) (PEG) hydrogels supported the deposition of key articular cartilage extracellular matrix (ECM) molecules. However, hydrogel degradation and mechanical loading induced loss of newly secreted ECM from the constructs, confirming that the mechanical environment is an essential consideration in designing hydrogels for cartilage tissue engineering. To reduce ECM loss, native polysaccharides and peptides that are involved in ECM assembly were encapsulated or covalently tethered in PEG hydrogels. The incorporation of these molecules reduced sulfated glycosaminoglycan loss and increased deposition of the main cartilage molecules, aggrecan and collagen II. Because PEG hydrogels have different mechanical behavior than cartilage under compressive loading and were formed by radical mediated polymerizations, questions arose about how hydrogel polymerization mechanism (i.e., step/chain growth) and subsequent hydrogel network structure (i.e., homogenous/heterogeneous) impact cartilage formation. Probing acrylate, chain-growth and thiol-norbornene, step-growth PEG hydrogels, showed that chondrocyte encapsulation in acrylate hydrogels reduced the final gel mechanical properties, led to increased intracellular ROS and hypertrophic cartilage. Under loading, more homogenous, thiol-norbornene hydrogel network structures produced articular cartilage-specific ECM with improved mechanical properties. This thesis demonstrates that the dynamic environment is an important component when designing biomaterials for cartilage tissue engineering and proposed techniques to alter hydrogel chemistry to retain cell-secreted ECM and to support the translation of mechanical cues to encapsulated cells.

Creator