High-throughput Bioprinting for Scalable and Biomimetic Human Tissues

Restricted (Penn State Only)
- Author:
- Kim, Myoung Hwan
- Graduate Program:
- Biomedical Engineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- October 07, 2024
- Committee Members:
- Ibrahim Ozbolat, Chair & Dissertation Advisor
Daniel Hayes, Major Field Member
Xiaojun Lian, Major Field Member
Zissis Chroneos, Outside Unit & Field Member
Daniel Hayes, Program Head/Chair - Keywords:
- Tissue fabrication
Bioprinting
Spheroid
Organoid
High-throughput
Biomimetic tissue
Disease model - Abstract:
- The demand for organ transplantation has significantly increased, yet the supply of viable donors remains critically limited, widening the disparity between those requiring transplants and available organs. This has driven advancements in tissue engineering and regenerative medicine, focusing on developing alternative solutions for organ replacement and building in vitro models that elucidate the intricate biological and pathological mechanisms within tissues and organs. Despite the progress, existing artificial tissues and devices still struggle to replicate the complexity and functionality of native tissues, creating limitations in successful tissue regeneration, scaled-up tissue fabrication, and accurate physiological and biological simulations. Tissues and organs are naturally sophisticated structures composed of three-dimensional (3D) layers made up of various cell types embedded within an extracellular matrix. Therefore, recapitulating these structures in 3D and fabricating functional tissues at scale is required to mimic native environments. Bioprinting has become a promising method in this regard, with its ability to engineer custom tissue models. Despite the development of various bioprinting techniques, significant limitations remain. These include potential cell damage during the bioprinting process, difficulty in achieving optimal cell density in the tissue, low-throughput, poor scalability, and inconsistency in reproducibility. To overcome these limitations, this dissertation focuses on the development of advanced bioprinting strategies designed for high-throughput tissue fabrication and biomimetic organoid development. Each chapter examines distinct strategies and applications—ranging from the development of support materials that enhance spheroid fusion, to methods for high-throughput scalable tissue fabrication, and even intraoperative bioprinting to generate direct deposition of patient-specific and defect-specific tissues for regeneration. Additionally, it explores the development of biomimetic distal lung organoids composed of induced pluripotent stem cell-derived alveolar epithelial cells to investigate lung alveologenesis and their susceptibility to viruses. The approaches presented in this dissertation have significant potential to broaden the accessibility and practicality across various tissue engineering domains. These include personalized, patient-specific tissue creation for regenerative treatments, improved in vitro models for drug testing, and more accurate systems for studying diseases. Ultimately, these advancements have the potential to shift from experimental techniques to clinical practice, radically transforming the field of medicine. Biomimetic tissues could significantly decrease, and eventually eliminate, the dependence on animal models for biomedical research, thus addressing both ethical and scientific challenges associated with preclinical testing.