Vascularization of hollow channel-modified porous silk scaffolds with endothelial cells for tissue regeneration.
Despite the promise for stem cell-based tissue engineering for regenerative therapy, slow and insufficient vascularization of large tissue constructs negatively impacts the survival and function of these transplanted cells. A combination of channeled porous silk scaffolds and prevascularization with endothelial cells was investigated to test the ability of this tissue engineering strategy to support rapid and extensive vascularization process. We report that hollow channels promote in vitro prevascularization by facilitating endothelial cell growth, VEGF secretion, and capillary-like tube formation. When implanted in vivo, the pre-established vascular networks in the hollow channel scaffolds anastomose with host vessels and exhibit accelerated vascular infiltration throughout the whole tissue construct, which provides timely and sufficient nutrients to ensure the survival of the transplanted stem cells. This tissue engineering strategy can promote the effective application of stem cell-based regeneration to improve future clinical applications.
Department of Prosthodontics, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China; Oral Bioengineering and Regenerative Medicine Lab, Shanghai Research Institute of Stomatology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China.
Wenjie
W
Zhang
Department of Biomedical Engineering, School of Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA.
Lindsay S
LS
Wray
Department of Biomedical Engineering, School of Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA.
Jelena
J
Rnjak-Kovacina
Department of Prosthodontics, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China; Oral Bioengineering and Regenerative Medicine Lab, Shanghai Research Institute of Stomatology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China.
Ling
L
Xu
Department of Dental Implant Centre, Stomatologic Hospital & College, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, 69 Meishan Road, Hefei 230032, China.
Duohong
D
Zou
Oral Bioengineering and Regenerative Medicine Lab, Shanghai Research Institute of Stomatology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China.
Shaoyi
S
Wang
Oral Bioengineering and Regenerative Medicine Lab, Shanghai Research Institute of Stomatology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China.
Maolin
M
Zhang
Oral Bioengineering and Regenerative Medicine Lab, Shanghai Research Institute of Stomatology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China.
Jiachen
J
Dong
Department of Prosthodontics, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China; Oral Bioengineering and Regenerative Medicine Lab, Shanghai Research Institute of Stomatology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China.
Guanglong
G
Li
Department of Biomedical Engineering, School of Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA. Electronic address: david.kaplan@tufts.edu.
David L
DL
Kaplan
Department of Prosthodontics, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China; Oral Bioengineering and Regenerative Medicine Lab, Shanghai Research Institute of Stomatology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China. Electronic address: xinquanj@aliyun.com.
Xinquan
X
Jiang
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D012831:Bombyx; D001854:Bone Marrow Cells / Q000166:cytology; D002470:Cell Survival; D017690:Cell Transplantation; D005349:Fibroins / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D016062:Porosity; D012038:Regeneration; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055114:X-Ray Microtomography
D001672:Biocompatible Materials; D042461:Vascular Endothelial Growth Factor A; D005349:Fibroins
Cell survival; Cell tracking; Regenerative medicine; Silk fibroin; Vascularization