Aaron Aziz
Student Alumni
Chemical Engineering

Osteochondral tissue engineering using multilayer hydrogel scaffolds to recapitulate the native layered structure serves as a promising strategy to repair and regenerate osteochondral defects due to joint trauma, injuries, and long-term diseases. The gold standard of clinical therapies relies on replacing the defect with autologous tissue from a non load-bearing site, yet engineered tissue often fails due to a lack of mechanical anchoring, donor site morbidity and tissue availability. Multilayered photopolymerizable poly(ethylene glycol) (PEG) hydrogels, with a bony layer that facilitates osteoconductivity and osseointegration present an opportunity to overcome these issues. Ensuring multilayer hydrogels supported bone growth within the native loading environment and encouraging degradation by multiple bone cells are some of the important challenges addressed herein.

The the goal of this thesis was to create a multilayer poly(ethylene glycol) (PEG) hydrogel platform, with a bony layer that facilitates cellular mediated degradation to allow for tissue elaboration and osteogenesis of encapsulated cells under physiologically relevant loading regimes. Initial work focused on developing a multilayer PEG hydrogel and characterizing said hydrogels as a function of hydrogel properties and fabrication methods. It was confirmed from multilayer hydrogel studies that a mechanically robust interface forms, but whose thickness can be controlled through the size of monomers and the crosslink density of preceding layers. Nanomechanical analysis confirmed that a gradient in modulus forms across the interface and subsequently leads to a gradual transfer of strain across the interface. Using the multilayer PEG hydrogel, it was demonstrated that a stiff bilayer hydrogel was capable of supporting osteogenesis of human mesenchymal stem cells (hMSCs) under compressive loads. These findings linked MAPK signaling to regulate mineralization in hMSCs under loading and further implicated the role of fluid flow, instead of strain, in fostering osteogenic differentiation of encapsulated cells in bilayer hydrogels. Finally, MMP-sensitive hydrogels were identified to support the osteogenic differentiation of both encapsulated hMSCs, as well as pre-osteocytes. This thesis demonstrated that cell-mediated degradation and loading within multilayer hydrogels can create an osteogenic scaffold to promote tissue regeneration for osteochondral tissue engineering applications.

Aaron received a BS from A. James Clark School of Engineering, University of Maryland. He majored in Chemical Engineering and Chemistry. He did his lab rotations in Dr. Stephanie Bryant's lab in Chemical and Biological Engineering, in Dr. Leslie Leinwand's lab in Molecular, Cellular and Developmental Biology, and in Dr. Christopher Bowman's lab in Chemical and Biological Engineering. Aaron graduated in Spring 2018.

Wahlquist JA, DelRio FW, Randolph MA, Aziz AH, Heveran CM, Bryant SJ, Corey PN, and Ferguson VL. Indentation mapping revealed poroelastic, but not viscoelastic, properties spanning native zonal articular cartilage. Acta Biomaterialia. 2017 Oct, ISSN 1742-7061, 10.1016/j.actbio.2017.10.003. (https://www.sciencedirect.com/science/article/pii/S1742706117306190)

Aziz AH, Wahlquist J, Sollner A, Ferguson V, DelRio FW, and Bryant SJ. Mechanical characterization of sequentially layered photo-clickable thiol-ene hydrogels. Journal of the Mechanical Behavior of Biomedical Materials. 2017 Jan, ISSN 1751-6161, 10.1016/j.jmbbm.2016.09.007. (http://www.sciencedirect.com/science/article/pii/S1751616116303137)

Kinneberg KRC, Nelson A, Stender ME, Aziz AH, Mozdzen LC, Harley BAC, Bryant SJ, and Ferguson VL. Reinforcement of Mono- and Bi-layer Poly(Ethylene Glycol) Hydrogels with a Fibrous Collagen Scaffold. Annals of Biomedical Engineering. 2015 May, ISSN 1573-9686, 10.1007/s10439-015-1337-0. (http://link.springer.com/article/10.1007%2Fs10439-015-1337-0)

Belai N, Harp BP, Mazzola EP, Lam Y, Abdeldayem E, Aziz A, Mossoba MM, and Barrows JN. Subsidiary colors in D&C Red No. 34 and its lakes: Synthesis, structural characterization, and analysis by ultra-performance liquid chromatography. Dyes and Pigments. 2012 Nov, 95(2) p.304-312, ISSN 0143-7208, 10.1016/j.dyepig.2012.05.001. (http://www.sciencedirect.com/science/article/pii/S014372081200126X)

Society for Biomaterials Annual Meeting                                                                            Apr 2017

Poster Presentation                                                                                                                 Denver, CO

World Biomaterials Congress Meeting                                                                                May 2016

Poster Presentation                                                                                                                 Denver, CO

Student Annual Research Symposium                                                                                Oct 2016

Oral Presentation                                                                                                                     Denver, CO

Photopolymerization Fundamentals Annual Meeting                                                        Sept 2015

Poster Presentation                                                                                                                 Denver, CO

Society for Biomaterials Annual Meeting                                                                            Apr 2014

Oral Presentation                                                                                                                     Denver, CO

Two-time CU Boulder Rec Bowling League Champions