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Development and Modification of Self-assembled Mesenchymal Stem Cells Aggregates for Musculoskeletal Tissue Engineering
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 박, 도영 | - |
| dc.contributor.author | 노, 수진 | - |
| dc.date.accessioned | 2025-01-17T06:43:22Z | - |
| dc.date.available | 2025-01-17T06:43:22Z | - |
| dc.date.issued | 2024 | - |
| dc.identifier.uri | http://repository.ajou.ac.kr/handle/201003/33693 | - |
| dc.language.iso | en | - |
| dc.title | Development and Modification of Self-assembled Mesenchymal Stem Cells Aggregates for Musculoskeletal Tissue Engineering | - |
| dc.title.alternative | 근골격계 조직공학을 위한 자가조립 활용 중간엽 줄기세포 집합체의 개발 및 변형 | - |
| dc.type | Thesis | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000033626 | - |
| dc.subject.keyword | Mesenchymal stem cells | - |
| dc.subject.keyword | Self-assembly | - |
| dc.subject.keyword | Decellularized extracellualr matrix | - |
| dc.subject.keyword | Bone-to-tendon interface | - |
| dc.subject.keyword | Fibrocartilage | - |
| dc.subject.keyword | Cartilage | - |
| dc.description.degree | Doctor | - |
| dc.contributor.department | 대학원 의생명과학과 | - |
| dc.contributor.affiliatedAuthor | 노, 수진 | - |
| dc.contributor.affiliatedAuthor | 박, 도영 | - |
| dc.date.awarded | 2024 | - |
| dc.type.local | Theses | - |
| dc.citation.date | 2024 | - |
| dc.embargo.liftdate | 9999-12-31 | - |
| dc.embargo.terms | 9999-12-31 | - |
| dc.description.tableOfContents | BACKGROUND 1
1.1. Mesenchymal stromal cells (MSCs) 2 1.1.1. Synovium-derived mesenchymal stem cells (SMSCs) 2 1.1.2. SMSCs for musculoskeletal tissue engineering 3 1.2. Self-assembly 4 1.2.1. Self-assembly techniques as recapitulation of early stage chondrogenesis 4 1.2.2. Musculoskeletal tissue engineering by using self-assembly techniques 5 1.3. Decellularized extracellular matrix (dECM) 6 1.3.1. dECM powder as one of formulation for tissue engineering approach 6 1.3.2. Decellularized cartilage and meniscus ECM powder 7 1.4. Thesis overview 8 CHAPTER I: Fabrication of scaffold-free fibrocartilage microtissues for bone-tendon interface healing 10 2.1. Introduction 11 2.2. Materials and methods 13 2.2.1. Isolation of synovial stem cells and cultivation of the cells 13 2.2.2. Fabrication of cell-based fibrocartilage microtissues without scaffold 13 2.2.3. Histological analysis of cell-based fibrocartilage constructs 15 2.2.4. Biochemical characterization of cell-based fibrocartilage constructs 15 2.2.5. Utilization of collagenase for tendon to fibrocartilage constructs integration 16 2.2.6. Evaluation of tendon to fibrocartilage constructs interface 16 2.2.7. Integration of tendon with a bone/cell-based fibrocartilage construct in vitro 17 2.2.8. Integration failure stress analysis 17 2.2.9. In vivo bone-to-tendon healing efficacy 18 2.2.10. Statistical analysis 19 2.3. Results 20 2.3.1. In vitro fabrication of cell-based fibrocartilage microtissues 20 2.3.2. Improvement of tendon integration with SMSCs after collagenase employment 22 2.3.3. In vitro integration evaluation of cell-based fibrocartilage microtissues 24 2.3.4. Effectiveness of cell-based fibrocartilage microtissues in bone-to-tendon repair in vivo 26 2.4. Discussion 28 CHAPTER II: Extracellular matrix-guided self-assembled meniscal microtissue engineering for replication of transitional meniscal tissue in a partial meniscectomy animal model 31 3.1. Introduction 32 3.2. Materials and methods 34 3.2.1. Isolation and culture of cells 34 3.2.2. Characterization of multipotency 34 3.2.3. Flow cytometry 35 3.2.4. The process for producing porcine acellular meniscal extracellular matrix (DMECM) 35 3.2.5. Engineering of self-assembled meniscal microtissues 36 3.2.6. Repression of self-assembly 37 3.2.7. Characterization of self-assembled microtissue with DMECM in vitro 37 3.2.8. Surgery for micropig meniscus defect model 39 3.2.9. Cell tracking for micropig meniscus defect model 40 3.2.10. Histological evaluation for micropig meniscus defect model 41 3.2.11. Biomechanical analysis for micropig meniscus defect model 42 3.2.12. Statistical analysis 43 3.3. Results 44 3.3.1. Optimization of cells concentration for engineering self-assembled microtissue 44 3.3.2. Optimization of DMECM concentration for engineering self-assembled microtissue 46 3.3.3. Developing meniscal microtissues using SMSCs and DMECM by self-assembly 48 3.3.4. Impacts on the self-assembly process at early differentiation and morphology 50 3.3.5. Effects of region-specific DMECM on maturity of meniscal microtissues by evaluating histological analysis 52 3.3.6. Effects of region-specific DMECM on maturity of meniscal microtissues by evaluating biochemical analysis 54 3.3.7. Effects of region-specific DMECM on maturity of meniscal microtissues by evaluating biomechanical analysis 56 3.3.8. Self-assembled microtissue as a meniscal filler and its handling for surgery 58 3.3.9. The effectiveness of a meniscal microtissues in a partially meniscectomized porcine model 60 3.3.10. Evaluation of mechanics related to tibiofemoral joint at the porcine model 63 3.3.11. Mechanical properties of regenerated meniscus 65 3.3.12. Evaluation of articular cartilage following a six-month implantation 67 3.4. Discussion 69 CHAPTER III: Preparation of printable cartilage tissue utilizing self-assembly of synovial stromal cells and decellularized cartilage extracellular matrix 74 4.1. Introduction 75 4.2. Materials and methods 77 4.2.1. Preparation of of decellularized cartilage extracellular matrix (DCECM) 77 4.2.2. Preparation of porcine synovium-derived stem cells 77 4.2.3. Fabrication of DCECM-guided self-assembled microtissue (DSA) 78 4.2.4. Physical characterization of DSA 80 4.2.5. Biological characterization of DSA 80 4.2.6. Biochemical characterization of DSA 81 4.2.7. Rheological characterization of DSA 82 4.2.8. Printing of DSA 82 4.2.9. Evaluation of printed constructs 83 4.2.10. Surgery for implantation of printed construct 84 4.2.11. Histologic analysis and cell tracking for implantation of printed construct 84 4.2.12. Biomechanical analysis for implantation of printed construct 85 4.2.13. Statistical analysis 85 4.3. Results 86 4.3.1. Optimization of DCECM concentration and DCECM size for fabrication of DSA 86 4.3.2. Characterization of DSA bioink 88 4.3.3. Rheological properties of DSA for 3D bioprinting 94 4.3.4. Printing condition adjustments 96 4.3.5. 3D bioprinting of DSA bioink 98 4.3.6. Evaluation of printed constructs 100 4.3.7. Implantation of printed construct using DSA bioink for porcine full-thickness cartilage defect model 102 4.3.8. pSMSCs tracking after 6-month implantation 105 4.4. Discussion 107 CONCLUSIONS 110 REFERENCES 112 국문요약 128 | - |
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