Injectable hydrogel loaded with functional SMP and FMP peptides for promoting stem cell migration and enhancing tissue organization
- 주제(키워드) Thermosensitive hydrogel , SMP peptide , FMP peptide , human mesenchymal stem cell recruitment , tissue regenration
- 주제(DDC) 547
- 발행기관 아주대학교 일반대학원
- 지도교수 Moon Suk Kim
- 발행년도 2026
- 학위수여년월 2026. 8
- 학위명 석사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000036572
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Recent advances in regenerative medicine have increasingly focused on biomaterial-based strategies that recruit stem cells to injury sites and promote tissue regeneration. In this study, a thermosensitive injectable hydrogel loaded with stem cell migration peptide （SMP） and fibroblast growth factor-mimetic peptide （FMP） was developed to induce stem cell recruitment and tissue organization. The hydrogel was synthesized using poly（ethylene glycol） （PEG） as an initiator with ε-caprolactone and isoambrettolide monomers, enabling thermosensitive behavior through the balance of hydrophilic and hydrophobic compositions. SMP and FMP were physically incorporated into the hydrogel to provide sustained biological activity following injection. Following implantation, SMP released from the hydrogel recruited intravenously administered human mesenchymal stem cells （hMSCs） to the target site, while the recruited stem cells promoted tissue organization and regenerative responses mediated by FMP. In vitro studies confirmed that SMP effectively enhanced stem cell migration. Furthermore, in vivo evaluation over a 4-week period demonstrated enhanced stem cell recruitment and tissue regeneration in the peptide-loaded hydrogel groups. Tissue regeneration was assessed through hematoxylin and eosin （H＆E） and Masson’s trichrome staining to evaluate tissue formation and collagen deposition. Immunofluorescence analyses were further performed to assess inflammatory responses （CD68）, stem cell recruitment （CD29 and CD44）, and angiogenesis- associated tissue organization （CD31）. Overall, this study presents a thermosensitive hydrogel-based regenerative strategy that sequentially promotes stem cell recruitment and tissue organization, suggesting its potential as a promising biomaterial platform for stem cell-based tissue regeneration. Keywords: Thermosensitive hydrogel, SMP peptide, FMP peptide, human mesenchymal stem cells recruitment, tissue regeneration.
more목차
1. Introduction 1
2. Experimental 3
2.1. Materials 3
2.2. Synthesis and Formulation of PCIA copolymers 4
2.3. Analysis of rheological properties for PCIA copolymers 5
2.4. Assessment of the injectability of thermosensitive PCIA hydrogels 6
2.5. Culturing human mesenchymal stem cells (hMSCs) in vitro 6
2.6. Preparation of fluorescence labeled hMSCs and NIH3T3. 6
2.7. In vitro cytotoxicity evaluation of FMP in hMSCs and NIH3T3 7
2.8. In vitro recruitment analysis using PKH-hMSCs by SDF1, SMP. 8
2.9. In vitro evaluation of ECM deposition in hMSCs treated with FMP. 8
2.10. Animal Experiments 9
2.11. Migration analysis of ICG-hMSCs in response to PCIA, SMP+PCIA and SMP/FMP+PCIA hydrogels 9
2.12. Histological evaluation of hydrogel explants using H&E and MTS staining 9
2.13. Immunofluorescence analysis of CD29, CD44, CD68, and CD31 expression in hydrogel implanted tissues. 11
3. Results & Discussion. 12
3.1. Synthesis and initial characterization of PCIA copolymers 12
3.2. Thermosensitive gelation behavior and injectability of PCIA hydrogels 13
3.3. In vitro evaluation of the cytocompatibility of FMP in hMSCs and NIH3T3 cells 15
3.4. In vitro wound healing assay to evaluate hMSCs migration in response to SDF1, SMP. 17
3.5. In vitro evaluation of ECM deposition and tissue organization in hMSCs by FMP 18
3.6. In vitro transwell migration assay of hMSCs toward SMP and FMP containing PCIA hydrogels 20
3.7. Tracking of ICG-labeled hMSCs migration in response to SMP+PCIA and SMP/FMP+PCIA hydrogels 22
3.8. Histological analysis of tissue regeneration using H&E and MTS 23
3.9. Immunofluorescence analysis of CD29 and CD44 positive stem cell recruitment around hydrogel sites 26
3.10. Immunofluorescence analysis of CD68-positive macrophage infiltration around hydrogel sites 27
3.11. Evaluation of neovascularization using CD31 immunofluorescence staining in hydrogel sites 29
4. Conclusion. 31
Reference 33
List of Publications. 35
List of Presentations. 36
