Enhancing cell proliferation in three-dimensional hydrogel scaffolds using digital light processing bioprinting technology

Three-dimensional (3D) bioprinting is gradually emerging as a popular technique driving as a new paradigm in tissue engineering. Enhancing cell proliferation and engraftment within volumetric 3D-bioprinted scaffolds is a key challenge in its implementation. However, basic exploratory studies on cell proliferation enhancement in 3D-bioprinted scaffolds using digital light processing (DLP) technology are still lacking. Traditionally, microchannels in scaffolds have been regarded as non-functional, empty spaces. In this paper, however, we propose that microchannels implanted in DLP-bioprinted scaffolds can provide space for cell proliferation, giving a new definition to microchannel function. To this end, we used fish gelatin methacrylate (F-GelMA) as a bioink with photocurable properties, followed by functional evaluation and optimization through rheological analysis. The morphology of DLP-printed scaffolds using the bioink was analyzed, and their biocompatibility was demonstrated through cell viability analysis. Microchannels of three different sizes were implanted to facilitate oxygenation, nutrient delivery, and media flow by addressing structural barriers identified via morphological analysis. Cell viability and proliferation rates in outer and inner microchannels were then comparatively analyzed. During the long-term culture period (about 5 weeks), the differences in proliferation rates due to changes in the media flow environment were assessed. The results demonstrated that cell survival, growth, and proliferation were significantly enhanced within the DLP-printed scaffolds in which the cells were encapsulated. This approach lends itself useful for basic exploratory study utilizing 3D culture technology in the realms of regenerative medicine and tissue engineering, where effective cell proliferation relative to the same volume is required.