Direct Freeform Fabrication of Seeded Hydrogels in Arbitrary Geometries

Abstract

A major challenge in tissue engineering is the generation of cell-seeded implants with structures that mimic native tissue, both in anatomic geometries and intratissue cell distributions. By combining the strengths of injection molding tissue engineering with those of solid freeform fabrication (SFF), three-dimensional (3-D) pre-seeded implants were fabricated without custom-tooling, enabling efficient production of patient-specific implants. The incorporation of SFF technology also enabled the fabrication of geometrically complex, multiple-material implants with spatially heterogeneous properties that would otherwise be challenging to produce. Utilizing a custom-built robotic SFF platform and gel deposition tools, alginate hydrogel was used with calcium sulfate as a crosslinking agent to produce pre-seeded living implants of arbitrary geometries. The process was determined to be sterile and viable at 94 +/- 5%. The GAG and hydroxyproline production was found to be similar to that of other implants fabricated using the same materials with different shaping methods. The geometric fidelity of the process was quantified by using the printing platform as a computerized measurement machine (CMM); the RMS surface roughness of printed samples in the z-dimension was found to be 0.16 +/- 0.02 mm.

Photochemical Patterning of Ionically Cross-Linked Hydrogels

“…The instantaneous cross-linking substantially complicates fabrication of more sophisticated structures necessary for drug release and cell scaffolding. To overcome this problem, formation of the hydrogel can be slowed down by using suspensions of weakly soluble calcium salts such as calcium carbonate [16] and calcium sulfate [18] allowing production of bulk calcium alginate hydrogels. Currently, the creation of responsive ionically cross-linked hydrogels is done mainly through utilization of their pH and thermal responses.…”

An Optical Method for Evaluation of Geometric Fidelity for Anatomically Shaped Tissue-Engineered Constructs

“…The feasibility of using medical imaging data to design tissue-engineered constructs has only been investigated very recently. 3,32 Similarly, over the past decade a number of efforts have demonstrated the utility of injection molding 3,11,30,33 and 3D tissue printing 17,20 in fabricating engineered tissues with complex geometry. Despite all this work there is limited information on the geometric accuracy of these techniques and how this geometric accuracy might compare between techniques.…”

“…Manual measurements are also time intensive and can result in damage to fragile implants such as hydrogels. Cohen et al 20 developed a method that compared engineered construct geometries using contact points throughout the hydrogel surface, whereby contact with the construct would complete an electrical circuit outputting an x-y-z location in 3D space. Building upon the work done by Cohen et al, a method could be developed that is automated, repeatable, and does not damage or contaminate the construct.…”

“…Having generated anatomically shaped menisci via injection molding 3 and 3D printing 20 in prior studies, our current objective was to quantify and compare shape fidelity between these two fabrication methods and to observe differences in constructs generated from MRI and microcomputed tomography (mCT) imaging modalities.…”

Fabrication and optimisation of a fused filament 3D-printed microfluidic platform

“…Fused deposition modelling (FDM) based 3D printers are readily available for purchase either as self-assembly kits or as pre-assembled units. While the use of 3D-printing to produce cost-effective tools for biomedical applications has significant potential [8,9], to date its use in the optical and biosensors field is limited.…”