Preclinical Evaluation of Medical Devices and Biomaterials: Safety and Efficacy Assessment Using Animal Models = 의료기기 및 생체재료의 전임상 평가: 동물모델을 이용한 안전성과 유효성 평가

다국어 초록 (Multilingual Abstract)

Modern surgical care, especially in plastic and reconstructive surgery, has been transformed by advances in surgical technologies and biomaterials. This dissertation presents a series of preclinical studies that systematically evaluate the safety, effectiveness, and clinical potential of emerging surgical devices and wound healing materials. Using animal models that closely resemble human anatomy and physiology, these studies provide critical translational insights for developing and approving new surgical interventions.

The first study evaluates the safety of common electrosurgical electrodes through controlled in vivo experiments on mini pig tissue. Through quantitative and histological analysis, the thermal damage caused by monopolar, bipolar, and argon plasma coagulation electrodes was assessed. This research established comparative safety profiles and identified optimal power settings and application times to minimize iatrogenic injury during surgical procedures. The second study examines a novel helium-argon plasma-based coagulation device designed to improve hemostasis while reducing thermal spread. Through both in vivo liver resection models and ex vivo tissue testing, this device demonstrated superior coagulative efficacy with minimized lateral thermal injury and acceptable safety margins across various energy settings. These results suggest promising potential for safe application in delicate surgical fields. The third study evaluates a supercritical carbon dioxide-processed acellular dermal matrix (sCO2-ADM) patch for wound healing and tissue regeneration. When tested in a full-thickness porcine skin wound model, the biomaterial demonstrated enhanced re-epithelialization, neovascularization, and collagen remodeling, confirming that the sCO2 process successfully preserved the extracellular matrix structure and bioactivity essential for regenerative healing.

Collectively, these studies establish a comprehensive preclinical framework for evaluating innovative surgical technologies. They highlight the importance of rigorous safety and efficacy testing in animal models and provide valuable data to guide the clinical translation of next-generation surgical devices and biomaterials.

국문 초록 (Abstract)

현대 외과 치료, 특히 성형외과 및 재건 수술 분야는 수술 기술과 생체재료의 발전에 따라 빠르게 변화하고 있습니다. 본 논문은 새로운 수술 기기 및 상처 치유 재료의 안전성, 유효성, 임상적 가능성을 체계적으로 평가한 일련의 전임상 연구 결과를 제시합니다. 해부학적 및 생리학적 특이성이 인간과 유사한 동물 모델을 활용하여, 본 연구는 차세대 수술 치료법의 개발 및 승인을 위한 중요한 중개 연구적 통찰을 제공합니다.

첫 번째 연구에서는 일반적으로 임상에서 사용되는 전기수술기의 안전성을 미니돼지 조직을 대상으로 한 생체 내 실험을 통해 평가하였습니다. 단극, 쌍극 및 아르곤 플라즈마 응고 전극에 의한 열 손상을 정량적 및 조직학적으로 분석하였으며, 이를 통해 안전성 프로파일을 수립하고, 수술 중 의료인에 조작에 따른 손상을 최소화할 수 있는 최적의 출력 설정 및 적용 시간을 제안하였습니다.

두 번째 연구에서는 지혈 효과를 개선하고 열 확산을 줄이기 위해 개발된 헬륨-아르곤 기반 플라즈마 응고 장치를 평가하였습니다. 생체 내 간 절제 모델과 생체 외 조직 실험을 통해 해당 장치는 우수한 응고 효과와 함께, 다양한 에너지 조건에서도 측방 열 손상이 최소화되는 안전한 적용 가능을 보여주었습니다. 이러한 결과는 민감한 수술 부위에서의 임상적 활용 가능성을 시사합니다.

세 번째 연구에서는 초임계 이산화탄소 공정을 이용해 제조된 무세포 진피 매트릭스 (sCO2-ADM) 패치를 상처 치유 및 조직 재생 목적으로 평가하였습니다. 전층 피부 결손이 유도된 돼지 모델에서 sCO2-ADM은 상피 재형성, 신생혈관 형성 및 콜라겐 재구성을 촉진하였으며, sCO2 공정이 세포외기질의 구조 및생물학적 활성을 효과적으로 보존하였음을 확인하였습니다.

본 연구는 혁신적인 수술 기술의 전임상 평가를 위한 포괄적인 연구 프레임워크를 제시하며, 동물 모델을 활용한 철저한 안전성과 유효성 검증의 중요성을 강조합니다. 또한 차세대 수술 기기 및 생체재료의 임상 전환을 위한 핵심 데이터를 제공합니다.

목차 (Table of Contents)

• Abstract i
• Table of Contents iii
• List of Abbreviations vii
• Chapter 1. Introduction 1
• 1.1 Study Background 1
• 2.2 Purpose of Research 4
• Chapter 2. Safety Assessment of Electrosurgical Electrodes by Using Mini Pig Tissue 5
• 2.1 Introduction 5
• 2.2 Materials and Methods 8
• 2.2.1 Materials 8
• 2.2.2 Animal preparation 8
• 2.2.3 Necropsy and tissue collection 9
• 2.2.4 Subject device treatment and thermal imaging analysis 9
• 2.2.5 Predicate device treatment and thermal imaging analysis 10
• 2.2.6 Histopathological analysis 10
• 2.2.7 Statistical analysis 11
• 2.3 Results 12
• 2.3.1 Animal observation 12
• 2.3.2 Thermography area analysis 12
• 2.3.3 The maximum temperature 15
• 2.3.4 The duration required to return to the basal temperature 17
• 2.3.5 Histopathological analysis 19
• 2.4 Discussion 23
• 2.5 Summary 26
• Chapter 3. Preclinical research on optimization and validation of the safety and effectiveness of a helium/argon generated plasma device 27
• 3.1 Introduction 27
• 3.2 Materials and Methods 30
• 3.2.1 Plasma equipment 30
• 3.2.2 Animal experiment 30
• 3.2.3 Skin surface temperature evaluation 33
• 3.2.4 Skin visual observation 33
• 3.2.5 Blood biochemical evaluation 33
• 3.2.6 Histopathological analysis 33
• 3.2.7 Evaluation of the coagulation area 34
• 3.2.8 Statistical analysis 34
• 3.3 Results 35
• 3.3.1 Experiment scheme and observation of the clinical value after plasma irradiation 35
• 3.3.2 Measurement of temperature change on the surface of pig skin immediately after plasma irradiation 38
• 3.3.3 Observation of the damage and healing process of the skin after application with the plasma device using a dermatoscope 41
• 3.3.4 Blood serum biochemistry test 43
• 3.3.5 Evaluation of inflammatory cell infiltration and epidermal proliferation of skin after plasma irradiation 47
• 3.3.6 Evaluation of the damage of collagen fibers in skin tissue after plasma irradiation 49
• 3.3.7 Evaluation of skin elasticity post-irradiation 51
• 3.4 Discussion 53
• 3.5 Summary 57
• Chapter 4. Supercritical Carbon Dioxide Processed Acellular Dermal Matrix Patch for Enhanced Wound Healing 58
• 4.1 Introduction 58
• 4.2 Materials and Methods 60
• 4.2.1 Supercritical carbon dioxide (sCO2) acellular dermal matrix (ADM) patch preparation 60
• 4.2.2 Scanning electron microscope (SEM) imaging for sCO2 ADM patch morphology 62
• 4.2.3 Tensile strength testing 62
• 4.2.4 Immunogenicity testing and component determination 62
• 4.2.5 Animal experiment 62
• 4.2.6 Measurement of the wound healing area 63
• 4.2.7 Histological analysis 64
• 4.2.8 Hematoxylin and eosin (H&E) staining 64
• 4.2.9 Masson's trichrome (MT) staining 64
• 4.2.10 Immunofluorescence (IF) staining 65
• 4.2.11 Protein preparation 65
• 4.2.12 Enzyme-linked immunosorbent assay (ELISA) 66
• 4.2.13 Nitric oxide quantification 66
• 4.2.14 2’, 7’-dichlorofluorescein diacetate assay (DCF-DA) 66
• 4.2.15 Reverse transcription polymerase chain reaction (RT-PCR) 67
• 4.2.16 Statistics analysis 68
• 4.3 Results 69
• 4.3.1 Characterization of sCO2 ADM patch 69
• 4.3.2 Macroscopic and microscopic observation of the wound healing process 72
• 4.3.3 Effects of the antiinflammation and antioxidation by sCO2 ADM patch during the wound healing process 80
• 4.3.4 Acceleration of the proliferation and remodeling by sCO2 ADM during the wound healing process 82
• 4.4 Discussion 87
• 4.5 Summary 90
• Chapter 5. Conclusions 91
• Bibliography 94
• Abstract in Korean 107