Spatial micropatterning of growth factors in three-dimensional hydrogels for location-specific regulation of cellular behaviors

摘要

Growth factors are potent stimuli for regulating cell function in tissue engineering strategies, but spatially patterning their presentation in three-dimensions (3D) in a facile manner using a single material is challenging. Micropatterning is an attractive tool to modulate the cellular microenvironment with various biochemical and physical cues and study their effects on stem cell behaviors. Implementing heparin’s ability to immobilize growth factors, dual-crosslinkable alginate hydrogels have been micropatterned in 3D with photocrosslinkable heparin substrates with various geometries and micropattern sizes, and their capability to establish 3D micropatterns of growth factors within the hydrogels was confirmed. This 3D micropatterning method could be applied to various heparin binding growth factors, such as FGFs, VEGF, TGF-βs and BMPs, while retaining the hydrogel’s natural degradability and cytocompability. Stem cells encapsulated within these micropatterned hydrogels have exhibited spatially localized growth and differentiation responses corresponding to various growth factor patterns, demonstrating the versatility of the approach in controlling stem cell behavior for tissue engineering and regenerative medicine applications.