The Tissue Engineering Grail: Seamless Biofabrication of Scaffold-free Hollow Constructs

Scaffold-free tissue engineering enables the construction of biomimetic tissues and organs by preserving cell-cell and cell-matrix interactions while avoiding exogenous scaffolds and biomaterials. Yet current approaches are limited to thin sheets or simple spheroids and often lack cellular maturity and organized extracellular matrix (ECM). Here, Anchored Cell Sheet Engineering, a concept that previously introduced anchors to guide the remodeling of cell sheets into more mature fibers or sheets, is extended to achieve seamless, single-step biofabrication of scaffold-free hollow tubular and spherical constructs for sustained biological and mechanical functions under physiological conditions. Using custom culture devices with curved geometries for two-dimensional (2D) culture, continuous confluent cell-ECM layers were formed that were then delaminated and guided by strategically positioned central cores with different shapes and sizes to undergo tension-mediated remodeling into mechanically stable hollow structures. This approach allows modulation of wall thickness, supports multi-layered architectures, and yields constructs capable of withstanding fluid flow. By expanding scaffold-free biofabrication beyond sheets and fibers to robust hollow geometries, this work establishes a versatile set of physiologically relevant building blocks for scalable bottom-up assembly of complex, multi-tissue organ-like constructs within a bioassembloid framework.