3D Bioprinting of Spatially Heterogeneous Collagen Constructs for Cartilage Tissue Engineering

Abstract

3D printing of biological tissues has been of increasing interest to the biomaterials community in part because of its potential to produce spatially heterogeneous constructs. Such technology is particularly promising for orthopedic applications, which require the generation of complex geometries to match patient anatomy and complex microstructures to produce spatial heterogeneity and anisotropy. Prior research has demonstrated the capacity to create precisely shaped 3D printed constructs using biocompatible alginate hydrogels. However, alginate is extremely compliant and brittle, and high-density collagen hydrogels could be a preferable option for load-bearing applications. This research focused on developing and evaluating a method of printing soft tissue implants with high-density collagen hydrogels using a commercially available 3D printer, modified for tissue-engineering purposes. The tissue constructs, seeded with primary meniscal fibrochondrocytes, were evaluated using measures of geometric fidelity, cell viability, mechanical properties, and fiber microstructure. The constructs were found to be mechanically stable and were able to support and maintain cell growth. Furthermore, heterogeneous 3D-printed constructs were generated, consisting of discrete domains with distinct mechanical properties.

3D printing for the design and fabrication of polymer-based gradient scaffolds

“…Although µCT is broadly used, a more simplistic technique recently described by Rhee et al . could be beneficial in cases where the overall scan size is too large and time consuming to acquire on a µCT [74]. In this technique, a hydrogel construct was lightly coated with charcoal powder to provide optical contrast before being imaged with a high-resolution, digitizing color scanner (3D Cyberware scanner) [74].…”

“…could be beneficial in cases where the overall scan size is too large and time consuming to acquire on a µCT [74]. In this technique, a hydrogel construct was lightly coated with charcoal powder to provide optical contrast before being imaged with a high-resolution, digitizing color scanner (3D Cyberware scanner) [74]. This technique provides lower resolution and lacks the internal scaffold view of a µCT scanner, but allows for a quick measurement of the geometry of a ~10 cm printed meniscus model down to 2 mm details.…”

“…This technique provides lower resolution and lacks the internal scaffold view of a µCT scanner, but allows for a quick measurement of the geometry of a ~10 cm printed meniscus model down to 2 mm details. Using this technique, the investigators were able to determine the accuracy of print as a function of collagen density as indicated by the percentage of scanned positions that were within 2 mm of target height [74]. …”

Micromechanical anisotropy and heterogeneity of the meniscus extracellular matrix

“…Unfortunately, similar to articular cartilage, the meniscus has limited self-healing capabilities, especially in the avascular, proteoglycan-rich inner zone [16]. To repair damaged meniscus and recover normal joint function, it is necessary not only to replicate the whole tissue morphology of the native meniscus [17], but also to restore its matrix structural heterogeneity at the nano-to-microscale [18], which is critical for the tissue to perform its specialized tissue-level properties [1]. To this end, it is imperative to understand the structure-mechanical function principles of the native meniscus ECM at multiple length scales [19].…”

3D bioprinting for cell culture and tissue fabrication

“…In another work by Stichler et al MSCs showed promising chondrogenic differentiation in the hybrid Hydrogels [66]. Furthermore, Rhee et al [67] developed soft cartilage tissue implants with collagen seeded with primary meniscal fibrochondrocytes, which were able to support and maintain cell growth.…”