Employing mineralized collagen scaffolds in a patient-centric approach for improved craniomaxillofacial bone repair

Critical sized craniomaxillofacial defects are a class of bone defects of the skull, neck or jaw that cannot heal naturally by the body, requiring surgical intervention. These types of defects can arise from congenital birth defects such as the cleft palate, cancer resection, and traumatic injuries from high energy impacts such as those in battlefield injuries. Clinical approaches to repair these defects, autografts and allografts, are inadequate due to limited tissue availability and increased risk of disease transmission, respectively. Biomaterials strategies have been developed to regenerate these large-scale defects. Our lab has developed a class of mineralized collagen scaffolds that promote osteogenesis in vitro and mineral deposition in vivo. However, in a recent critical sized in vivo large animal mandibular study we observed poor healing due to increased inflammatory response and poor cell infiltration, osteogenesis, and vascular growth. Thus, there is a need to develop immunomodulatory biomaterials that can direct cell response in a spatiotemporal manner while resolving inflammation and enhancing regeneration. The local wound microenvironment comprises of a highly heterogeneous cell population that constantly undergoes a complex dialogue and is influenced by the local inflammatory state. Understanding the role of these crosstalk interactions and inflammatory state on immune, stem, and endothelial cell response will inform novel biomaterial design approaches for improved repair. Further, this heterogeneity is not limited to the cellular level but extends to the patient level based on characteristics such as sex, age, race, and co-morbidities that influence healing capacity. This thesis focuses on modifying mineralized collagen scaffolds to enhance immunomodulatory properties while employing them as an in vitro platform to understand crosstalk interactions and patient variability. We first describe material changes regarding composition such as the addition of placental derived membranes, or variation of glycosaminoglycan type, and structure by varying pore size and shape, with the goal to improve mesenchymal stem cell immunomodulation and guide immune cell polarization. Further, we elucidate crosstalk interactions between mesenchymal stem cells and immune cells under basal and inflammatory conditions to evaluate the effect of inflammation on cell behavior and crosstalk. Finally, we conducted a comprehensive study of donor variability within our materials with the goal of discerning the effect of sex on mesenchymal stem cell osteogenic response while probing the influence of female sex hormones on stem cell regenerative capacity. Overall, this dissertation describes material changes that can provide local immunomodulation while illuminating opportunities for biomaterial development via the understanding of multi-cell interactions and patient heterogeneity.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemical Engineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2023

Author dc:creator

• Kolliopoulos, Aliki

Contributors dc:contributor

• Harley, Brendan A
• Leckband, Deborah E
• Diao, Ying
• Spiller, Kara

• Tissue Engineering
• Regenerative Medicine
• Biomaterials
• Immunomodulatory
• Mineralized Collagen Scaffolds
• Macrophage
• Mesenchymal Stem Cell

Statement dc:rights

• © 2023 Vasiliki K. Kolliopoulos. All rights reserved.

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/121221

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F121221