Novel technology for simple assembly of aligned 3D cellular collagen materials for tissue engineering

摘要

Many tissues (e.g. nervous system, cardiac and musculoskeletal) have anisotropic structures and cellular alignment is fundamental to their function. Mimicking tissue anisotropy is important in tissue engineering, but achieving robust alignment of cells in a hydrogel matrix is challenging. Here we report a new technique, combining cellular self-alignment in collagen gels with a simple method of stabilising the aligned cellular gels, to produce biomimetic aligned tissues without the use of pre-formed scaffolds. Cells are seeded in 2 mg/ml type-I collagen gels and tethered at opposite ends of a rectangular mould. After 12–24 hours of incubation uniaxial tension develops within the collagen gel, resulting in cells aligning parallel to the axis of principal strain. We stabilise the aligned cellular construct using controlled compression and absorption (RAFT Real Architecture for 3D Tissue). The resulting tissues have physiologically relevant collagen concentrations and cells remain highly aligned even after removal of tethering. This approach, which can be scaled-up and automated, provides a powerful new way to produce aligned cellular biomaterials.We have developed and tested it using nervous system cells to provide Engineered Neural Tissue for repair and modelling of both the CNS and peripheral nerves. Our data demonstrate its broad potential for tissue engineering, where robust and stable cellular alignment is required for repair and as better tissue models for research.