Photocrosslinkable hyaluronan-gelatin hydrogels for two-step bioprinting

Tissue Eng Part A. 2010 Aug;16(8):2675-85. doi: 10.1089/ten.TEA.2009.0798.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biomimetic Materials / chemical synthesis*
  • Cell Culture Techniques / methods*
  • Cell Proliferation
  • Cell Separation / methods*
  • Cell Survival
  • Cross-Linking Reagents / chemical synthesis
  • Cross-Linking Reagents / radiation effects
  • Extracellular Matrix / chemistry*
  • Extracellular Matrix / radiation effects
  • Gelatin / chemical synthesis*
  • Gelatin / pharmacology
  • Gelatin / radiation effects
  • Hyaluronic Acid / chemical synthesis*
  • Hyaluronic Acid / pharmacology
  • Hyaluronic Acid / radiation effects
  • Hydrogels / chemical synthesis
  • Hydrogels / pharmacology
  • Hydrogels / radiation effects
  • Light
  • Materials Testing
  • Mice
  • Mice, Nude
  • Micromanipulation / methods*

Substances

  • Cross-Linking Reagents
  • Hydrogels
  • Gelatin
  • Hyaluronic Acid