Hydrosoluble, UV-crosslinkable and injectable chitosan for patterned cell-laden microgel and rapid transdermal curing hydrogel in vivo.
Natural and biodegradable chitosan with unique amino groups has found widespread applications in tissue engineering and drug delivery. However, its applications have been limited by the poor solubility of native chitosan in neutral pH solution, which subsequently fails to achieve cell-laden hydrogel at physiological pH. To address this, we incorporated UV crosslinking ability in chitosan, allowing fabrication of patterned cell-laden and rapid transdermal curing hydrogel in vivo. The hydrosoluble, UV crosslinkable and injectable N-methacryloyl chitosan (N-MAC) was synthesized via single-step chemoselective N-acylation reaction, which simultaneously endowed chitosan with well solubility in neutral pH solution, UV crosslinkable ability and injectability. The solubility of N-MAC in neutral pH solution increased 2.21-fold with substitution degree increasing from 10.9% to 28.4%. The N-MAC allowed fabrication of cell-laden microgels with on-demand patterns via photolithography, and the cell viability in N-MAC hydrogel maintained 96.3 ± 1.3% N-MAC allowed rapid transdermal curing hydrogel in vivo within 60s through minimally invasive clinical surgery. Histological analysis revealed that low-dose UV irradiation hardly induced skin injury and acute inflammatory response disappeared after 7 days. N-MAC would allow rapid, robust and cost-effective fabrication of patterned cell-laden polysaccharide microgels with unique amino groups serving as building blocks for tissue engineering and rapid transdermal curing hydrogel in vivo for localized and sustained protein delivery.
Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150001, PR China; Bio-acoustic MEMS in Medicine Laboratory, Department of Medicine, Division of Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. Electronic address: libq@hit.edu.cn.
Baoqiang
B
Li
Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150001, PR China.
Lei
L
Wang
MOE Key Laboratory of Biomedical Information Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China.
Feng
F
Xu
Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150001, PR China.
Xiaomin
X
Gang
Stanford University School of Medicine, Radiology Department, Canary Center at Stanford for Cancer Early Detection, Palo Alto, CA 94304, USA.
Utkan
U
Demirci
Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150001, PR China.
Daqing
D
Wei
Sino-Russian Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China; Heilongjiang Academy of Medical Sciences, Harbin 150001, PR China.
Ying
Y
Li
Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150001, PR China.
Yujie
Y
Feng
Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150001, PR China.
Dechang
D
Jia
Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150001, PR China.
Yu
Y
Zhou
D000279:Administration, Cutaneous; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007267:Injections; D051379:Mice; D041681:NIH 3T3 Cells; D010316:Particle Size; D012995:Solubility; D014466:Ultraviolet Rays; D014867:Water / Q000737:chemistry*
D003432:Cross-Linking Reagents; D014867:Water; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D048271:Chitosan
Injectability; Localized delivery; Patterned microgels; Photolithography; Transdermal photopolymerization