Flow Simulation and Gradient Printing of Fluorapatite- and Cell-Loaded Recombinant Spider Silk Hydrogels

Abstract

Hierarchical structures are abundant in almost all tissues of the human body. Therefore, it is highly important for tissue engineering approaches to mimic such structures if a gain of function of the new tissue is intended. Here, the hierarchical structures of the so-called enthesis, a gradient tissue located between tendon and bone, were in focus. Bridging the mechanical properties from soft to hard secures a perfect force transmission from the muscle to the skeleton upon locomotion. This study aimed at a novel method of bioprinting to generate gradient biomaterial constructs with a focus on the evaluation of the gradient printing process. First, a numerical approach was used to simulate gradient formation by computational flow as a prerequisite for experimental bioprinting of gradients. Then, hydrogels were printed in a single cartridge printing set-up to transfer the findings to biomedically relevant materials. First, composites of recombinant spider silk hydrogels with fluorapatite rods were used to generate mineralized gradients. Then, fibroblasts were encapsulated in the recombinant spider silk-fluorapatite hydrogels and gradually printed using unloaded spider silk hydrogels as the second component. Thereby, adjustable gradient features were achieved, and multimaterial constructs were generated. The process is suitable for the generation of gradient materials, e.g., for tissue engineering applications such as at the tendon/bone interface.

Biomimetic gradient scaffolds for the tissue engineering and regeneration of rotator cuff enthesis

“…In recent decades, biomimetic scaffolds for TBI regeneration have been made from a variety of materials, including natural polymers, synthetic polymers, bioceramics, and composite materials [60][61][62][63][64][65][66]. Collagen is the most commonly used natural polymer due to its prominence in the ECM with minimal host immune response [67,68].…”

Anatomical Tissue Engineering of the Anterior Cruciate Ligament Entheses

“…Bioprinting is a technique that allows cells encapsulated in an ink to be placed at defined areas of a TE construct, with the ink mimicking the abundant ECM in the ACL and its enthesis. Combining functionalized inks allows adjustable gradients to be created as described by Neubauer et al [113]. In this study, composites of recombinant spider silk hydrogels with fluorapatite rods were used to generate mineralized gradients.…”