Document Type
Dissertation
Date of Award
5-31-2021
Degree Name
Doctor of Philosophy in Biomedical Engineering - (Ph.D.)
Department
Biomedical Engineering
First Advisor
Treena Livingston Arinzeh
Second Advisor
Eduardo A.C. Almeida
Third Advisor
George Collins
Fourth Advisor
Eun Jung Lee
Fifth Advisor
James P. O’Connor
Sixth Advisor
Pranela Rameshwar
Abstract
Autologous and allogeneic bone grafts are currently used to treat large bone defects or fractures that will not heal. However, for patients with osteoporosis or other conditions that impair the natural bone healing process, such as diabetes, smoking, bed rest, aging, autologous bone graft, which is the patient's own bone, is limited in quantity and its healing potential may be compromised. Allograft bone, or donated bone, lacks the necessary biological activity and has poor integration into defect. There is an urgent need for constructs/grafts capable of promoting bone cell function in fracture healing and large bone defects where the endogenous healing process is impaired. The development of tissue engineering scaffolds seeks to alleviate these challenges.
In this work, plant derived materials are fabricated into fibrous scaffolds that could mimic the architecture and composition of the native bone extracellular matrix (ECM) to enhance bone cell activity under normal gravity and hypergravity conditions. Zein, a corn protein, has been shown to promote osteogenesis in vitro and in vivo, however, electrospun zein lacks hydrolytic stability. Sulfated GAGs have been suggested to influence the osteogenic differentiation of bone precursor cells and inhibit osteoclastogenesis. Here, carrageenans, a family of plant derived sulfated polysaccharides that resemble the chemical structure of sulfated GAGs are incorporated into electrospun zein scaffolds. To achieve hydrolytically stable fibrous scaffolds, this work identifies trimethylolpropane triglycidyl ether (TMPGE) as a successful crosslinker to zein protein and carrageenan without adverse effects to cell viability. Pre-osteoblasts and mesenchymal stem cells on scaffolds display enhanced cell growth, promoted osteogenic differentiation by elevated alkaline phosphatase (ALP) activity, enhanced collagen matrix deposition and maturation, and upregulation of bone markers (RUNX2, collagen Type I, osteopontin, osteoprotegerin and osteocalcin). The cells on scaffolds also displayed enhanced mineralization, and reduction of factors that induce bone resorption (RANKL, sRANKL/OPG ratio and GDF15). Further, evidence suggests that osteoblasts favor kappa-carrageenan that resembles the sulfated GAG in mature bone, while stem cells favor lambda-carrageenan which resembles the sulfated GAG in bone marrow. Additionally, the scaffolds and hypergravity by centrifugation have a synergistic effect on cell proliferation, collagen matrix deposition, and osteogenic differentiation and mineralization. Findings demonstrate that the plant-derived scaffolds hold promise for bone tissue engineering and bone repair strategies.
Recommended Citation
Turner, Jessica Cardenas, "Plant-derived extracellular matrix mimetic scaffolds for bone repair applications" (2021). Dissertations. 1784.
https://digitalcommons.njit.edu/dissertations/1784
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