MULTI-MATERIAL STEREOLITHOGRAPHY: SPATIALLY-CONTROLLED BIOACTIVE POLY(ETHYLENE GLYCOL) SCAFFOLDS FOR TISSUE ENGINEERING

摘要

Challenges remain in tissue engineering to control the spatial and temporal mechanical and biochemical architectures of scaffolds. Unique capabilities of stereolithography (SL) for fabricating multi-material spatially-controlled bioactive scaffolds were explored in this work. To accomplish multi-material builds with implantable materials, a new mini-vat setup was designed, constructed and placed on top of the existing build platform to allow for accurate and self-aligning X-Y registration during fabrication. Precise quantities of photocrosslinkable solution were added to and removed from the mini-vat using micro-pipettes. The mini-vat setup allowed the part to be easily removed and rinsed and different photocrosslinkable solutions could be easily removed and added to the vat to aid in multi-material fabrication. Two photocrosslinkable hydrogel biopolymers, poly(ethylene glycol dimethacrylate) (PEG-dma, molecular wt 1,000) and poly(ethylene glycol)-diacrylate (PEG-da, molecular wt 3,400), were used as the primary scaffold materials, and controlled concentrations of fluorescently labeled dextran or bioactive PEG were prescribed and fabricated in different regions of the scaffold using SL. The equilibrium swelling behavior of the two biopolymers after SL fabrication was determined and used to design constructs with the specified dimensions at the swollen state. Two methods were used to measure the spatial gradients enabled by this process with multi-material spatial control successfully demonstrated down to 500-μm. First, the presence of the fluorescent component in specific regions of the scaffold was analyzed with fluorescent microscopy. Second, human dermal fibroblast cells were seeded on top of the fabricated scaffolds with selective bioactivity, and phase contrast microscopy images were used to show specific localization of cells in the regions patterned with bioactive PEG. The use of multi-material SL and the relative ease of conjugating different bioactive ligands or growth factors to PEG allows for the fabrication of tailored three-dimensional constructs with specified spatially-controlled bioactivity.