Cell surface engineering for conformal encapsulation
Restricted (Penn State Only)
- Author:
- Lee, Kyungsene
- Graduate Program:
- Biomedical Engineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- January 16, 2025
- Committee Members:
- Paul Cremer, Outside Unit & Field Member
Peter Butler, Major Field Member
Yuguo Lei, Major Field Member
Yong Wang, Chair & Dissertation Advisor
Daniel Hayes, Program Head/Chair - Keywords:
- Cell surface engineering
Cell encapsulation
Conformal coating
Type 1 diabetes - Abstract:
- Cell therapy has become a transformative approach in medical science, offering the potential to treat a wide range of diseases and injuries by introducing live, functional cells that repair or replace damaged tissues and restore normal function. This dissertation advances cell therapy through the development of a biomimetic zona pellucida (BZP) encapsulation platform, inspired by the natural protective barrier surrounding mammalian eggs. Unlike traditional encapsulation methods that rely on bulk hydrogels or thick capsules—which limit oxygen, nutrient, and waste transport—the BZP platform uses a thin, conformal coating to provide selective permeability, structural stability, and immunoprotection. The BZP encapsulation, formed directly on cell surfaces through aptamer-mediated recognition and crosslinking, achieves 100% encapsulation efficiency without complex equipment or harsh conditions, thereby preserving cell viability and function. The encapsulation process involves immobilizing thrombin on the cell surface via DNA aptamer binding, forming a fibrin matrix, and subsequently embedding alginate followed by polylysine crosslinking to develop the BZP coating. This protective, biocompatible approach allows essential molecular exchange while maintaining cell integrity under physiological conditions. After demonstrating successful BZP formation on microparticles, this platform was applied to living mammalian cells and cell spheroids, specifically mesenchymal stem cell (MSC) spheroids, to explore its versatility in regenerative medicine. BZP-coated MSC spheroids exhibit selective permeability that protects against immune cell attacks while retaining critical functions such as cytokine secretion and differentiation. Under hypoxic conditions, BZP-coated MSCs enhance the secretion of angiogenic factors, while immunomodulatory assays show that BZP encapsulation promotes anti-inflammatory macrophage polarization. This work further extends BZP applications to MSC spheroids for angiogenesis and pancreatic islets for type 1 diabetes treatment in animal models. Mice transplanted with BZP-coated MSC spheroids showed enhanced blood vessel formation compared to uncoated spheroids. In diabetic mice, BZP-coated islets achieved superior long-term glycemic control, with 80% of mice maintaining normoglycemia for over 54 days. Additionally, zwitterionic modifications to the BZP coating improved graft survival and glucose clearance, demonstrating BZP’s potential to enhance islet transplantation outcomes. In conclusion, this research establishes BZP encapsulation as a robust and adaptable platform for cell-based therapies. Its broad applicability in regenerative medicine and transplant viability underscores its promise for applications beyond type 1 diabetes.