Access Type

Open Access Thesis

Date of Award

January 2023

Degree Type

Thesis

Degree Name

M.S.

Department

Chemical Engineering and Materials Science

First Advisor

Howard W. Matthew

Abstract

Osteoarthritis remains a poorly treatable outcome of traumatic cartilage injury as cartilage is unable to self-repair. Unfortunately, roughly 10% of all adults in the United States have been diagnosed with osteoarthritis although the true fraction is likely at least 30%. While the main focus of osteoarthritis research has been on treating damage to the cartilage, osteoarthritis will also lead to damage to the adjacent trabecular bone due to wear via shearing down of the tissue’s surface. Considering this, in conjuncture with transplanted cartilages’ inability to integrate into the native tissue, unlike the surrounding bone, the significance of a combined osteochondral implant cannot be underestimated. When considering the functional drawbacks of traditional, non-biological implants, the benefit of regenerating native tissue becomes clear. Issues with traditional scaffolds, namely size limitations due to poor nutrient and oxygen diffusion, have proven the usefulness of a modular approach to this problem.In the following work, we aim to address the issues associated with bone loss using a modular tissue engineering approach. The focus of this work is on the promotion of osteogenesis in hollow microcapsules composed of chitosan and glycosaminoglycans formed via complex coacervation, as well as the assembly of the resultant organoids into an effective, implantable construct. We investigated the effects of the inclusion of hyaluronan and collagen-derived gels on the promotion of osteogenesis in said microcapsules and showed increases in mineral deposition on the microcapsule membranes, as well as increases in protein production by the cells. Investigation into an interior collagen-based gel that was able to inhibit cell-mediated contraction was also conducted, in an attempt to generate a more biomimetic microenvironment. For this purpose, it was found that gelatin methacrylate served as an effective material. Additionally, with the significant interaction between bone and surrounding vasculature, we investigated the role that microvascular endothelial cells have on mineralization and protein production during osteogenesis, as well as the effects modified dextran sulfate and collagen have on these microvascular endothelial cells. Endothelial cell interactions proved useful in the promotion of osteogenesis, and surface modifications enhanced cell morphology and performance on microcapsule exteriors, as well as increasing cellular proliferative rates. Lastly, we sought to develop a method to rapidly fuse microcapsules within a defect site. For this, we found the use of crosslinked, methacrylated polymers, deposited on the microcapsule exterior, to be a viable method. These materials were shown to be effective at generating fused constructs, with no observable impact on cellular function. We hope this work will further progress the solution to this complex problem.

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