Fabrication of a spray-type anti- inflammatory hydrogel and its efficacy as an adhesion barrier = 분사형 항염증 하이드로겔의 개발과 유착방지제로써의 효과

다국어 초록 (Multilingual Abstract)

Gastrointestinal surgery commonly leads to post-operative adhesions, causing severe complications. To prevent these adhesions, a crucial step is the application of a physical barrier between the peritoneal wall and organs. Despite various adhesion barriers available, some have limitations like off-target placement, complex usage, or prolonged application. This study introduces a novel spray-type adhesion barrier hydrogel that addresses these issues. The barrier, featuring a dual gelation system, forms a polyelectrolyte complex and undergoes gel-sol transition for stability. Remarkably, it remains effective in vivo for over 28 days and exhibits anti-inflammatory properties, which aids the regeneration process by modulating the peritoneal environment. In a rat ischemic button model, the barrier showed immunomodulatory potential by shifting macrophages from M1 to M2 state. In conclusion, this rapid and efficient adhesion barrier shows promise in mitigating post-surgical adhesions. Keyword : Adhesion, Anti-Inflammation, Sprayable Hydrogel, Biocompatible, Rapid Gelation Student Number : 2022-22621

국문 초록 (Abstract)

복강 내에서 이루어지는 수술은 흔히 수술 후 유착으로 이어지고, 재수술과 같은 문제점을 야기한다. 유착을 방지하기 위해서는 물리적인 장벽을 복벽과 장기 사이에 세우는 것이 중요하다. 다양한 유착 방지제에도 불구하고, 아직까지도 오프 타겟 현상, 사용의 번거로움, 사용 시간의 장기화 등이 문제가 되고 있다. 이런 문제들에 착안하여 새로운 분사형 유착 방지제 하이드로겔을 개발하는 연구를 진행하였다. 이 유착 방지제는 이중 겔화 구조를 갖고 있으며, 고체 전해질 복합체를 형성 후 액체에서 겔화 된다. 이 하이드로겔은 체내에서 28일 이상 효과를 보이고 항염증성 특징을 띄어 재생 과정에 영향을 미친다. 랫트
허혈성 버튼 모델에서 이 유착 방지제는 면역조절 특징을 보였고, 상처 부위의 대식 세포를 M1에서 M2 형질로 바꾸었다. 결과적으로 이 분사형 하이드로겔은 효과적인 새로운 유착 방지제로서 사용될 잠재력을 보인다.

목차 (Table of Contents)

• Chapter 1. Background 1
• 1.1 Peritoneal Adhesion and Inflammation 1
• Chapter 2. Anti-inflammatory rapid gelling spray type
• hydrogel adhesion barrier . 4
• 2.1 Introduction . 4
• 2.2 Experimental Procedures 9
• 2.2.1 Materials 9
• 2.2.2 Fabrication of HA-TBA 10
• 2.2.3 Fabrication of sHA 10
• 2.2.4 Fluorescent labeling of sHA and CS . 11
• 2.2.5 sHACSF preparation 12
• 2.2.6 Mechanical characterization of sHACSF 12
• 2.2.7 Gelation condition evaluation . 13
• 2.2.8 Sprayability evaluation 13
• 2.2.9 In vitro cytocompatibility . 14
• 2.2.10 Immunocytochemistry 14
• 2.2.11 In vivo cytocompatibility 15
• 2.2.12 In vivo retention study 16
• 2.2.13 sHACSF efficacy in rat models . 16
• 2.2.14 In vivo retention in rat models 17
• 2.2.15 Histology . 17
• 2.2.16 Immunohistochemistry 17
• 2.2.17 Quantification of rat cytokine levels 18
• 2.2.18 Statistical analysis 18
• 2.3 Results and Discussion 18
• 2.3.1 Fatbrication and characterization of sHA 18
• 2.3.2 Formulation of sHACSF 19
• 2.3.3 Characterization of sHACSF 20
• 2.3.4 In vitro biocompatibility and immunomodulatory
• effects 21
• 2.3.5 Biocompatibility and retention kinetics in mouse
• models 23
• 2.3.6 Therapeutic effects in rat peritoneal adhesion 24
• 2.3.7 Histological analysis and in vivo immunomodulatory
• function of sHACSF 25
• iii
• Chapter 3. Conclusion 27
• Figures 29
• 1. Scheme 29
• 2. Analysis of mechanical characterisctics 30
• 2.1 Gelation condition screening 30
• 2.2 Rheological analysis 31
• 2.3 Sprayability evaluation 32
• 3. In vitro biocompatibility and immunomodulatory function of
• sHACSF 33
• 3.1 Biocompatibility . 33
• 3.2 Immunocytochemistry 34
• 3.3 Quantification of TNF-α 35
• 4. Biocompatibility and retention kinetics in mouse models 36
• 4.1 Biocompatibility in mouse models 36
• 4.2 Retention studies in mouse models 37
• 5. Prevention of rat peritoneal adhesion using sHACSF 38
• 5.1 Prevention of adhesion in rat models using sHACSF . 38
• 5.2 Histological analysis 39
• 5.3 Adhesion quantificatoin . 40
• 5.4 Retention studies in rat models 41
• 6. Histological analysis and in vivo immunomodulatory
• function of sHACSF 42
• 6.1 Immunohistochemistry 42
• 6.2 M1/M2 quantifications 42
• 6.2 Rat cytokine quantification . 43
• Bibliography 44
• Abstract in Korean . 45