Author ORCID Identifier
0000-0003-3809-1609
Document Type
Dissertation
Date of Award
12-31-2022
Degree Name
Doctor of Philosophy in Biomedical Engineering - (Ph.D.)
Department
Biomedical Engineering
First Advisor
Treena Livingston Arinzeh
Second Advisor
Bryan J. Pfister
Third Advisor
Pranela Rameshwar
Fourth Advisor
James P. O’Connor
Fifth Advisor
Courtney Karner
Abstract
More than 500,000 bone grafting procedures are performed each year to treat bone defects, trauma, and non-unions. Current strategies, including autografts and allografts, face limitations that include donor site morbidity and poor integration, respectively. Treatments using the delivery of the growth factor, bone morphogenetic protein-2 (BMP2), result in ectopic bone formation and adverse effects at high doses. Tissue engineering strategies are utilized to combat these challenges. Natural biomaterials are commonly used as tissue engineering scaffolds due to their biocompatibility, biodegradability, and they can promote cellular function. However, animal-derived materials can have limitations in availability, lot to lot variability and potential immunogenic response. The following studies utilize a novel metabolic approach utilizing a corn-derived protein zein as a potential tissue engineering scaffold material for bone repair. Comparisons are made with animal-derived gelatin, which is denatured collagen and widely used as a biomaterial. Zein is rich in glutamine, which plays a major role in cell growth and osteogenesis, biodegradable and has been shown to promote osteogenesis of bone progenitors. Results demonstrate that zein scaffolds promoted MSC (human mesenchymal stem cells) growth, migration and osteogenesis when compared to gelatin scaffolds.
Scaffolds enriched in metabolic factors by crosslinking with citric acid (CA), a component of the tricarboxylic cycle (TCA) are fabricated. Zein scaffolds, either crosslinked with CA or trimethylolpropane triglycidyl ether (TMPGE), an epoxide, are challenged in conditions without metabolic factors (glucose, glutamine, sodium pyruvate) and demonstrate robust MSC cell growth and osteogenesis. Studies inhibiting glutamine metabolism further demonstrate zein's glutamine contribution to cell growth and osteogenesis.
Zein scaffolds are evaluated in vivo in an subcutaneous model and compared with commercially available gelatin foam, SurgiFoam®. Quantitative analysis of CD31, a marker for angiogenesis, and Ki67, a proliferation marker, determine MSC loaded TMPGE crosslinked zein scaffolds show enhanced angiogenesis and cell proliferation as compared to cell-free scaffolds. No differences are observed in the SurgiFoam® groups suggesting that TMPGE crosslinked zein scaffolds are viable carriers for MSCs. Overall, these studies demonstrate zein as a potential plant-derived alternative for gelatin for bone tissue engineering applications. Additionally, these studies determine zein scaffolds can provide metabolic factors such as glutamine and is utilized by MSCs. Findings demonstrate that zein scaffolds are promising for bone repair strategies.
Recommended Citation
Limaye, Apurva, "Naturally derived fibrous scaffolds containing metabolic factors for bone tissue engineering" (2022). Dissertations. 1919.
https://digitalcommons.njit.edu/dissertations/1919
