Engineered Janus Patches with Adhesive and Anti-Adhesive Surfaces for Selective Tissue Interfacing = 선택적 조직 인터페이싱을 위한 접착/비접착 표면을 갖는 공학적 야누스 패치

국문 초록 (Abstract)

패치 기반 솔루션은 코스메틱부터 의료기기에 이르기까지 바이오산업 전반에서 폭넓게 활용되고 있다. 그러나 특정 임상 및 응용 환경에서는 하나의 패치가 표적 부위에는 강한 고정력을 제공하면서도, 주변 조직에는 비특이적 부착을 최소화해야 하는 상충 요구를 동시에 충족해야 한다. 일반적으로 접착과 항접착 기능은 동일한 재료 또는 동일 표면에서 트레이드오프 관계에 있으므로, 두 기능을 한 패치 내에서 공간적으로 분리하는 이중 표면(dual-surface) 설계가 필수적이다. 본 학위논문에서는 선택적 조직 인터페이싱(Selective Tissue Interfacing, STI) 구현을 목표로, 접착과 항접착 요구를 패치의 서로 다른 표면에 매핑하면서도 패치 전체의 구조적 일체성 및 제조 재현성을 유지하는 Janus(이중 표면) 패치를 설계하였다. 접착면은 PCL 기반 머쉬룸(mushroom) 미세구조를 적용하여 기계적 인터로킹과 박리 저항을 통해 표적 부위 고정을 강화하도록 설계하였다. 항접착면은 초기 전략으로 PEG 기반 UV 코팅을 적용하였으며, 접촉각 및 FT-IR 분석을 통해 젖음성 변화와 화학적 시그니처 변화를 기반으로 PEG 표면 개질이 이루어졌음을 확인하였다. 한편, 코팅 기반 항접착의 번역(translation) 및 스케일업 관점의 한계를 고려하여, 플랫폼을 고도화하는 과정에서 PEG 전략을 마이크로니들(microneedle) 기반 항접착 표면으로 대체하였다. 해당 항접착 구조는 접촉 면적, 구조 간격, 계면 마찰을 제어함으로써 주변 조직에 대한 비특이적 부착을 감소시키도록 설계되었으며, 젖은 환경에서 패턴의 안정성 및 형상 재현성을 확보하는 동시에 조직 위험을 최소화하고 제조 가능성을 유지할 수 있도록 기하학적 파라미터를 최적화하였다.
본 논문에서는 기능 분리형 검증 체계를 구축하여 구조-기능 상관성을 단계적으로 확인하였다. 먼저 구조적 특성평가를 통해 기하학적 형상과 균일성을 확인하고, 접착/항접착 성능이 구조 설계에 의해 유도됨을 검증하였다. 또한 인장 시험, 건조/습윤 접착 시험 및 ex vivo 버스팅 압력 시험을 통해 패치의 기계적 일체성, 취급 강건성, 고정력 및 습윤 조건에서의 압력 저항성·누수 방지 밀봉 성능을 평가하였다. 생물학적 안전성과 표면 기능의 구분을 위해 세포 생존율, Live/Dead 염색, Phalloidin/DAPI 염색을 수행하여 세포독성 여부를 확인하고, 항접착면에서 관찰되는 부착 감소가 독성에 의한 현상이 아님을 구분하였다. 더 나아가 RT-qPCR을 통해 패치 또는 표면 개질이 세포 반응을 유전자 발현 수준에서 어떻게 조절하는지 정량화함으로써, 관찰된 효과가 단순한 부착량 차이가 아니라 분자 수준의 변화와 연관됨을 확인하였다. 마지막으로, 독립 배치 간 재현성 분석을 포함하여 기하학적 구조와 성능의 일관성을 검증함으로써, 신뢰 가능한 제조 및 향후 번역·스케일업 가능성을 뒷받침하였다. 본 연구는 접착과 항접착 기능을 하나의 패치에 공간적으로 분리·통합하는 STI 지향 Janus 패치 설계 및 검증 프레임워크를 제시하며, 다양한 바이오·의료 응용 환경에서 요구되는 선택적 조직 인터페이스 구현을 위한 공학적 설계 전략으로서의 가능성을 제시한다.

다국어 초록 (Multilingual Abstract)

Patch-based solutions are used broadly across the bio-industry, spanning cosmetics to medical devices. However, in certain clinical and application settings, a single patch is required to provide firm fixation at a target site while simultaneously minimizing unwanted, non-specific attachment to surrounding tissues. Because adhesion and anti- adhesion are inherently trade-off functions on one material or surface, a dual-surface design that spatially separates functions is essential to meet these conflicting requirements. In this thesis, engineered Janus (dual-surface) patches were designed for Selective Tissue Interfacing (STI) by mapping the two requirements to distinct surfaces while maintaining whole-patch integrity and reproducibility. The adhesive side was implemented using a PCL mushroom microtopography, intended to enhance anchoring via mechanical interlocking and peel resistance. For the anti-adhesive side, a PEG UV coating strategy was used as an initial approach, and successful PEG surface modification was verified by contact angle and FT-IR through changes in wettability and chemical signatures. Recognizing translation/scale-up concerns associated with coating-based anti-adhesion, the platform was further upgraded by replacing the PEG approach with a microneedle-based anti-adhesive surface, which is designed to reduce non-specific attachment by controlling contact, spacing, and interfacial friction geometric parameters were optimized to ensure pattern fidelity and stability under wet conditions while minimizing tissue risk and preserving fabrication feasibility. A function-separated validation framework was established, including structural characterization to confirm geometry and uniformity and to link adhesion/anti-adhesion performance directly to structure. Mechanical integrity and application-relevant performance were evaluated using tensile, adhesion (dry/wet), and ex vivo bursting pressure tests to assess handling robustness, fixation strength, and pressure-resistant sealing/leakage-proof fixation under wet conditions. In vitro assays (cell viability, Live/Dead, and Phalloidin/DAPI staining) were performed to confirm cytocompatibility and to distinguish anti-adhesive reduced attachment from true cytotoxicity. RT-qPCR was conducted to quantify how the patch or surface modification modulates cellular responses at the gene-expression level and to verify that observed effects reflect molecular changes rather than merely differences in cell attachment. Finally, reproducibility analysis was included to confirm consistent geometry and performance across independent batches, supporting reliable manufacturing and translational scalability.
Keywords: Janus patch, Selective Tissue Interfacing, Adhesion/Anti-adhesion, PCL

목차 (Table of Contents)

• Abstract
• 1. Chapter 1. Introduction 1
• 1.1. General Introduction 1
• 1.2. Objectives 3
• 1.3. References 5
• 2. Chapter 2. Literature Review 7
• 2.1. Engineering Problem Definition: Patch Interfaces and Conflicting Requirements 7
• 2.2. Janus Technology as an Engineering Framework for Spatial Functional Separation 10
• 2.3. Micro- and Nanotopographical Engineering for Selective Tissue Interfacing 13
• 2.3.1. Cell-matrix interactions and mechanotransduction as design foundations 14
• 2.3.2. Bioinspired adhesive microstructures for structure-driven anchoring 15
• 2.3.3. Anti-adhesive micro/nanotopographies and contact-geometry control 16
• 2.3.4. Integrating dual topographies for STI: toward robust, quantifiable selectivity 17
• 2.4. Micro- and Nanotopographical Engineering of Tissue Interfaces 19
• 2.4.1. Cell-matrix interactions and mechanotransduction 19
• 2.4.2. Bioinspired adhesive and anti-adhesive microstructures 20
• 2.4.3. Hierarchical topographies for differential tissue responses 21
• 2.4.4. Engineering implementation for STI-driven Janus patches: requirement mapping, geometry constraints, and validation 22
• 2.5. Biodegradable Polymer Systems for STI-Oriented Patches 24
• 2.5.1. Synthetic aliphatic polyesters as patternable structural backbones: PLGA and PCL 24
• 2.5.2. Interfacial tuning polymers: PEG for anti-adhesion and chitosan for bioactive modulation 25
• 2.5.3. Hybrid material strategies and polymer expansion for dual-surface performance 26
• 2.6. Challenges and Future Prospects 27
• 2.6.1. Translation-limiting factors as engineering constraints 27
• 2.6.2. Standardization and quantification gaps for anti-adhesion performance 27
• 2.6.3. Summary of knowledge gaps motivating the present thesis 28
• 2.7. References 30
• 3. Chapter 3. PCL Mushroom Microtopography and PEG UV Coating for Dual-Surface Functionality 33
• 3.1. Summary 33
• 3.2. Introduction 35
• 3.3. Materials and Methods 39
• 3.3.1. Materials and preparation of patterned molds 39
• 3.3.2. Fabrication of PCL mushroom microstructures 39
• 3.3.3. PEG spin coating and UV curing on the back surface 40
• 3.3.4. Structural and physicochemical characterization 41
• 3.3.5. Mechanical testing and adhesion/anti-adhesion evaluation 41
• 3.3.6. In vitro biocompatibility and cell adhesion assays 42
• 3.3.7. RT-qPCR analysis and reproducibility analysis 43
• 3.4. Results and Discussion 44
• 3.4.1. Morphology and surface chemistry of the PCL/PEG Janus patch 44
• 3.4.2. Mechanical properties and dual-surface adhesion behavior 45
• 3.4.3. Pressure-resistant sealing under wet ex vivo conditions 46
• 3.4.4. In vitro cytocompatibility and surface-dependent cell responses 46
• 3.4.5. Design implications for STI-oriented dual-surface patches 47
• 3.5. Conclusion 49
• 3.6. References 62
• 4. Chapter 4. Dual-Functional Ultratiny-Patterned Janus Patch 64
• 4.1. Summary 65
• 4.2. Introduction 67
• 4.3. Materials and Methods 70
• 4.3.1. Patch architecture and microtopography design 70
• 4.3.2. Master fabrication and PDMS negative molds 70
• 4.3.3. Polymer solution preparation 71
• 4.3.4. Soft-lithographic fabrication of Janus patches 71
• 4.3.5. Physicochemical characterization (FT-IR and SEM) 72
• 4.3.6. Mechanical testing (uniaxial tensile) 72
• 4.3.7. In vitro cytocompatibility and cell-surface interaction assays 73
• 4.3.8. Ex vivo tissue adhesion testing 73
• 4.3.9. Ex vivo bursting pressure test (sealing evaluation) 74
• 4.3.10. Manufacturing repeatability 74
• 4.4. Results and Discussion 75
• 4.4.1. Dual-surface microtopography realized by soft lithography 75
• 4.4.2. Chemical integrity of PLGA/chitosan constructs after processing 75
• 4.4.3. Mechanical robustness relevant to handling and placement 76
• 4.4.4. Mushroom-face adhesion on synthetic substrates under dry and wet conditions 76
• 4.4.5. Microsharp-face anti-adhesion and asymmetry of interfacial behavior 77
• 4.4.6. Ex vivo tissue adhesion: translation from synthetic benchmarks to biological substrates 77
• 4.4.7. Cytocompatibility and face-dependent cell morphology 78
• 4.4.8. Gene-expression readouts associated with wound-healing signaling 78
• 4.4.9. Ex vivo sealing capability under pressure loading 79
• 4.4.10. Manufacturing repeatability as an engineering metric 79
• 4.4.11. Integrated interpretation: proof-of-concept validation of STI via dual microtopography 79
• 4.5. Conclusion 82
• 4.6. References 99
• 5. Concluding Remarks 100
• Abstract (Korean) 105