Photocrosslinkable hyaluronan-gelatin hydrogels for two-step bioprinting.
Bioprinting by the codeposition of cells and biomaterials is constrained by the availability of printable materials. Herein we describe a novel macromonomer, a new two-step photocrosslinking strategy, and the use of a simple rapid prototyping system to print a proof-of-concept tubular construct. First, we synthesized the methacrylated ethanolamide derivative of gelatin (GE-MA). Second, partial photochemical cocrosslinking of GE-MA with methacrylated hyaluronic acid (HA-MA) gave an extrudable gel-like fluid. Third, the new HA-MA:GE-MA hydrogels were biocompatible, supporting cell attachment and proliferation of HepG2 C3A, Int-407, and NIH 3T3 cells in vitro. Moreover, hydrogels injected subcutaneously in nude mice produced no inflammatory response. Fourth, using the Fab@Home printing system, we printed a tubular tissue construct. The partially crosslinked hydrogels were extruded from a syringe into a designed base layer, and irradiated again to create a firmer structure. The computer-driven protocol was iterated to complete a cellularized tubular construct with a cell-free core and a cell-free structural halo. Cells encapsulated within this printed construct were viable in culture, and gradually remodeled the synthetic extracellular matrix environment to a naturally secreted extracellular matrix. This two-step photocrosslinkable biomaterial addresses an unmet need for printable hydrogels useful in tissue engineering.
Skardal
Aleksander
A
Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA.
Zhang
Jianxing
J
McCoard
Lindsi
L
Xu
Xiaoyu
X
Oottamasathien
Siam
S
Prestwich
Glenn D
GD
D000818:Animals; D040761:Biomimetic Materials / Q000138:chemical synthesis*; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods*; D002470:Cell Survival; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000528:radiation effects; D005109:Extracellular Matrix / Q000737:chemistry* / Q000528:radiation effects; D005780:Gelatin / Q000138:chemical synthesis* / Q000494:pharmacology / Q000528:radiation effects; D006820:Hyaluronic Acid / Q000138:chemical synthesis* / Q000494:pharmacology / Q000528:radiation effects; D020100:Hydrogels / Q000138:chemical synthesis / Q000494:pharmacology / Q000528:radiation effects; D008027:Light; D008422:Materials Testing; D051379:Mice; D008819:Mice, Nude; D008846:Micromanipulation / Q000379:methods*
D003432:Cross-Linking Reagents; D020100:Hydrogels; D005780:Gelatin; D006820:Hyaluronic Acid
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