A Versatile Method to Produce Monomodal Nano- to Micro-Fiber Fragments as Fillers for Biofabrication

Abstract

A key goal of biofabrication is the production of 3D tissue models with biomimetic properties. In natural tissues, fibrils—mainly composed of collagen—play a critical role in stabilizing and spatially organizing the extracellular matrix. To use biomimetic fibers for reinforcing bioinks in 3D printing, fiber fragmentation is necessary to prevent nozzle clogging. However, existing fragmentation methods are often material-specific, poorly scalable, and provide limited control over fragment size and shape. A novel workflow is introduced for producing fiber fragments applicable to various materials and fabrication techniques such as electrospinning, melt-electrowriting, fused deposition modeling, wet spinning, and microfluidic spinning. The method uses a sacrificial membrane as a substrate for precise cryo-sectioning of fibers. A significant advantage is that no additional handling steps, such as fiber detachment or transfer, are needed, resulting in highly reproducible fiber sectioning with a quasi-monodisperse length distribution. The membrane can be rolled before cutting, preventing fibers from sticking together and significantly increasing production efficiency. This method is also versatile, applicable to multiple fiber types and materials without re-parameterization. Cell culture experiments demonstrate that the fibers maintain key properties necessary for cell-fiber interactions, making them suitable for systematic screenings in the development of anisotropic 3D tissue models.