한빛사논문
- 조회862
Jong-Eun Wona,b, Yun Sang Leeb, Jeong-Hui Parka,d, Jung-Hwan Leea,d,e,f, Yoo Seob Shinb,c,*, Chul-Ho Kimb,c,*, Jonathan C. Knowelsd,e,g, Hae-Won Kima,d,e,f,*
a Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 31116, Republic of Korea
b Department of Otolaryngology, School of Medicine, Ajou University, Suwon 16499, Republic of Korea
c Department of Molecular Science & Technology, Ajou University, Suwon 16499, Republic of Korea
d UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan 31116, Republic of Korea
e Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine; Republic of Korea
f Department of Biomaterials Science, College of Dentistry, Cheonan 31116, Republic of Korea
g Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, 256 Grays Inn Road, London WC1X 8LD, Republic of Korea
*Corresponding author : Yoo Seob Shin, Chul-Ho Kim, Hae-Won Kim
Abstract
Recapitulating the in vivo microenvironments of damaged tissues through modulation of the physicochemical properties of scaffolds can boost endogenous regenerative capacity. A series of critical events in tissue healing including immune-responses, angiogenesis, and stem cell homing and differentiation orchestrate to relay the regeneration process. Herein, we report hierarchically structured (‘microchanneled’) 3D printed scaffolds (named ‘μCh’), in contrast to conventional 3D printed scaffolds, induce such cellular responses in a unique way that contributes to accelerated tissue repair and remodeling. The μCh reduced the extracellular trap formation of anchored neutrophils at the very beginning (24 h) of implantation while increasing the number of live cells. Among the macrophages covered the surface of μCh over 7 days a major population polarized toward alternativelly activated phase (M2) which contrasted with control scaffolds where classically activated phase (M1) being dominant. The mesenchymal stem cells (MSCs) recruited to the μCh were significantly more than those to the control, and the event was correlated with the increased level of stem cell homing cytokine, stromal derived factor 1 (SDF1) sequestered to the μCh. Furthermore, the neo-blood vessel formation was more pronounced in the μCh, which was in line with the piling up of angiogenic factor, vascular endothelial growth factor (VEGF) in the μCh. Further assays on the protein sequestration to the μCh revealed that a set of chemokines involved in early pro-inflammatory responses were less found whereas representative adhesive proteins engaged in the cell-matrix interactions were significantly more captured. Ultimately, the fibrous capsule formation on the μCh was reduced with respect to the control, when assessed for up to 21 days, indicating less severe foreign body reaction. The tissue healing and regenerative capacity of the μCh was then confirmed in a critically sized bone model, where those series of events observed are essential to relay bone regeneration. The results over 6 weeks showed that the μCh significantly enhanced the early bone matrix deposition and accelerated bone regeneration. While more in-depth studies remain as to elucidate the underlying mechanisms for each biological event, the molecular, cellular and tissue reactions to the μCh were coherently favorable for the regeneration process of tissues, supporting the engineered scaffolds as potential therapeutic 3D platforms.
Graphical abstract
Hierarchically structured (microchanneled) 3D printed scaffold (‘μCh’), demonstrating the orchestrated biological events of immune/inflammation-modulation, pro-angiogenesis, and stem cell homing, promises potential therapeutic 3D platforms for accelerating tissue repair and regeneration.
Keywords : Tissue microenvironment; Microchanneled scaffolds; Immune responses; Stem cell homing; Angiogenesis; Protein sequestration
논문정보
- Research article
- 2019년 10월 (BRIC 등록일 2019-10-25)
- 국내 연구진
- 의약학 > 재생의학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
관련분야 논문보기
