Date Approved
11-28-2022
Embargo Period
12-5-2023
Document Type
Dissertation
Degree Name
Ph.D. Doctor of Philosophy
Department
Biomedical Engineering
College
Henry M. Rowan College of Engineering
Advisor
Sebastian L. Vega, Ph.D.
Committee Member 1
Amir Miri, Ph.D.
Committee Member 2
Erik Brewer, Ph.D.
Committee Member 3
Rachel Riley, Ph.D.
Committee Member 4
Tae Won Kim, M.D.
Keywords
biochemical modification, Diels-Alder chemistry, gelatin, hyaluronic acid, injectable hydrogels, peptides
Subject(s)
Biomedical materials; Colloids in medicine; Bioactive compounds
Disciplines
Biomedical Engineering and Bioengineering
Abstract
Hydrogels are soft biomaterials that feature a wide range of physical and biochemical properties. Although highly versatile, hydrogels typically require an exogeneous input (e.g., light, pH, temperature) to form, and this limits their use to conditions where a catalyst is present. The goal of this dissertation is to expand the use of catalyst-based hydrogels by developing hydrogels with independently tunable properties which gel in situ without external stimuli. This new class of hydrogels was developed by first modifying macromers with norbornene (Nor) or tetrazine (Tet) moieties. Macromers containing Nor or Tet remain liquid when dissolved, and upon mixing self-form into Nor-Tet hydrogels. Hydrogels with broad mechanical properties are obtained, and peptide functionalization has no effect on mechanics or gelation time. Nor-Tet hydrogels functionalized with adhesive RGD peptides exhibit exceptional cell-matrix interactions, and stem cells in Nor-Tet solutions are protected from shear forces cells experience during liquid cell injections. Nor-Tet hydrogels functionalized with peptides containing active motifs of bone morphogenetic protein 2 (BMP2) also induce 3D osteogenic differentiation, and BMP2 Nor-Tet hydrogel injections into medullary cavities result in nascent trabecular bone growth in femurs. Taken together, the self-forming Nor-Tet hydrogels developed can be used to safely deliver cells in vivo and can serve as a targeted therapeutic to locally treat degenerative musculoskeletal diseases including osteoporosis.
Recommended Citation
Gultian Giddings, Kirstene Arcuino, "BIOACTIVE SELF-FORMING HYDROGELS FOR BIOMEDICAL APPLICATIONS" (2022). Theses and Dissertations. 3073.
https://rdw.rowan.edu/etd/3073