PhD Dissertation Defense
Thursday, May 22, 2025
Gateway Park 1002
9:00am-10:00am
"Development of Iron Chelated Silk Fibroin Microfibers as an Injectable, Magnetically Aligning Nerve Guidance Architecture”
Melissa Wojnowski
Abstract: An alarming disparity persists between the incidence and prevalence of traumatic spinal cord injury (SCI). While only18,000 new cases are reported annually, an estimated 300,000 individuals nationwide are currently living with chronic unresolving spinal cord trauma. With minimal spontaneous neuroregeneration and no clinically available cure, the least likely prognosis for SCI patients, attained in only 0.5% of cases, is complete neurological recovery.
Comprehensive neurological recovery requires synergy between innate neuroprotective mechanisms and interventional neuroregenerative therapies. Aiming to combine the neuroprotective benefits of minimally invasive delivery and the neuroregenerative benefits of a lesion-bridging biomaterial scaffold, this dissertation reports the development of an injectable, in situ aligning nerve guidance architecture: iron chelated silk fibroin microfibers (Fe3+-mSF).
Herein, the fibrous structure and metal binding capacity of silk fibroin was leveraged to synthesize a magneto-responsive architecture without the need for magnetic nanoparticles (MNPs). By comparison to nascent mSF, Fe3+-mSF exhibited both increased magnetization potential and greater alignment uniformity in an externally applied magnetic field. When incorporated into hyaluronic acid-based hydrogels, Fe3+-mSF did not alter hydrogel syringeability, critical gelation time, viscoelastic properties, or swelling profile, indicating preservation of gross biomechanical properties essential to minimally invasive delivery. Fe3+-mSF cytocompatibility was demonstrated both as an independent biomaterial (2D culture) and as an architectural component of a collagen hydrogel (3D scaffold). Notably, incorporation of aligned Fe3+-mSF into collagen hydrogels seemed to correlate with upregulated expression of TUBB3 (β-tubulin III), a key neuroregenerative biomarker for axonal outgrowth and elongation. Finally, in a proof-of-principle study, Fe3+-mSF/hydrogel scaffolds were successfully aligned in vitro on the patient bed of an MRI machine, showcasing the translational potential of this biomaterial design in a clinically relevant setting.
To our knowledge, this work is the first to investigate the magneto-responsive properties, minimally invasive delivery, and neuroregenerative potential of Fe3+-mSF, thereby demonstrating a novel, MNP-free approach in the design of an in situ aligning nerve guidance architecture.
| Dissertation Advisor: | Committee Chair: | ||
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Jeannine Coburn, PhD Associate Professor Biomedical Engineering Worcester Polytechnic Institute
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Kris Billiar, PhD Professor and Department Head Biomedical Engineering Worcester Polytechnic Institute |
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| Defense Committee: | |||
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Dirk Albrecht, PhD Associate Professor Biomedical Engineering Worcester Polytechnic Institute |
Ronald Grimm, PhD Associate Professor Chemistry and Biochemistry Worcester Polytechnic Institute |
Juan Belran-Huarac, PhD Assistant Professor Physics East Carolina University |
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For a zoom link, please email kharrison@wpi.edu