A Study of Variable Stiffness Alginate Printing for Medical Applications

Technologies for multi-material 3D-printing of anatomical shapes are useful both for fabrication of heterogeneous cell-seeded implants as well as for fabrication of synthetic models for surgical planning and training. For both these applications, it would be desirable to print directly with biological materials to best emulate the target’s properties. Using a novel material platform, we describe a series of experiments attempting to print variable-stiffness hydrogels. We vary compliances by alternating 2% alginate hydrogel and a Dextran-infused calcium chloride post-crosslinker. Stiffness throughout the construct ranged from 4 kPa to 20 kPa as a function of post-crosslinker concentration, which was spatially specified by the user. Introduction Technologies for multi-material 3D-printing of anatomical shapes are useful both for fabrication of heterogeneous cell-seeded implants as well as for fabrication of synthetic models for surgical planning and training [9]. Currently, printed implants typically consist of single compliance, high stiffness materials such as metals and polymers. These materials are not suitable for emulating heterogeneous tissue such as a heart valve, where a wide range of mechanical stiffnesses are required [11]. Additionally, many of these materials cannot act as tissue engineering constructs because they are not biocompatible [13, 19, 22]. At the same time, soft materials have yet to be extensively applied in SFF for the purpose of surgical planning. In order for a practitioner to plan an approach to the target site, a comprehensive understanding of the spatial orientations of structures is critical. In normal anatomies, experience alone can be relied upon. However, in complicated cases including trauma and rare pathologies, anatomies are often highly abnormal, and, therefore, difficult for surgeons to navigate in-situ without prior advanced study [6]. Consequently, it is highly beneficial to provide real 3D models for a surgeon to analyze, and practice upon, prior to surgery [8, 22]. Rapid prototyping using alginate hydrogels is a method for fabricating bioimplants and surgical planning. Complex models can be produced relatively quickly where time is critical [5, 6, 7, 10]. Up until now, single compliance models are not only unsuitable to use for printing multi-compliance parts (e.g., heart valves), but also insufficient for re-creating key tactile cues required for surgical planning [10, 20]. Furthermore, since these models are rather stiff, it is difficult to practice procedures such as incisions and suturing [10, 20, 22]. Lastly, since many of these materials are not biocompatible, cells cannot be seeded into the material to fabricate tissue engineering scaffolds [13, 21, 22, 24, 25].