A Synthetic Dynamic PVA Photoresin for Fast Volumetric Bioprinting of Functional Ultrasoft Hydrogel Constructs

Abstract

Tomographic volumetric bioprinting (VBP) enables fast photofabrication of cell-laden hydrogel constructs in one step, addressing the limitations of conventional layer-by-layer additive manufacturing. However, existing biomaterials that fulfill the physicochemical requirements of VBP are limited to gelatin-based photoresins of high polymer concentrations. The printed microenvironments are predominantly static and stiff, lacking sufficient capacity to support 3D cell growth. We here report a dynamic resin based on thiol-ene photo-clickable polyvinyl alcohol (PVA) and thermo-sensitive sacrificial gelatin for fast VBP of functional ultrasoft cell-laden hydrogel constructs within 7-15 seconds. Using gelatin allows VBP of permissive hydrogels with low PVA contents of 1.5%, providing a stress-relaxing environment for fast cell spreading, 3D osteogenic differentiation of embedded human mesenchymal stem cells and matrix mineralization. Additionally, site-specific immobilization of molecules-of-interest inside a PVA hydrogel is achieved by 4D tomographic thiol-ene photopatterning. This technique may enable spatiotemporal control of cell-material interactions and guided in vitro tissue formation using programmed cell-friendly light. Altogether, this study introduces a synthetic dynamic photoresin enabling fast VBP of functional ultrasoft hydrogel constructs with well-defined physicochemical properties and high efficiency.