Three-Dimensional-Printed Flexible Scaffolds Have Tunable Biomimetic Mechanical Properties for Intervertebral Disc Tissue Engineering

Abstract

The intervertebral disc (IVD) exhibits complex structure and biomechanical function, which supports the weight of the body and permits motion. Surgical treatments for IVD degeneration (e.g., lumbar fusion, disc replacement) often disrupt the mechanical environment of the spine which lead to adjacent segment disease. Alternatively, disc tissue engineering strategies, where cell-seeded hydrogels or fibrous biomaterials are cultured in vitro to promote matrix deposition, do not recapitulate the complex IVD mechanical properties. In this study, we use 3D printing of flexible polylactic acid (FPLA) to fabricate a viscoelastic scaffold with tunable biomimetic mechanics for whole spine motion segment applications. We optimized the mechanical properties of the scaffolds for equilibrium and dynamic moduli in compression and tension by varying fiber spacing or porosity, generating scaffolds with de novo mechanical properties within the physiological range of spine motion segments. The biodegradation analysis of the 3D printed scaffolds showed that FPLA exhibits lower degradation rate and thus has longer mechanical stability than standard PLA. FPLA scaffolds were biocompatible, supporting viability of nucleus pulposus (NP) cells in 2D and in FPLA+hydrogel composites. Composite scaffolds cultured with NP cells maintained baseline physiological mechanical properties and promoted matrix deposition up to 8 weeks in culture. Mesenchymal stromal cells (MSCs) cultured on FPLA adhered to the scaffold and exhibited fibrocartilaginous differentiation. These results demonstrate for the first time that 3D printed FPLA scaffolds have de novo viscoelastic mechanical properties that match the native IVD motion segment in both tension and compression and have the potential to be used as a mechanically stable and biocompatible biomaterial for engineered disc replacement.

Aggressive strategies for regenerating intervertebral discs: stimulus-responsive composite hydrogels from single to multiscale delivery systems

“…It can maintain the activity of NPCs and promote their ECM deposition over time. 271 It is an ideal material for the construction of artificial IVD tissues. To make IVD constructs more ''intelligent'', a multiscale delivery system constructed by cross-linking stimuli-responsive composite hydrogels with micron/nanoparticles can serve not only as an ideal bioink for 3D printing but also as a multifunctional scaffold that mimics natural IVD tissue and allows for long-term cell proliferation and differentiation and the controlled release of drugs/biological factors.…”

Emerging polymeric material strategies for cartilage repair

“…Whole disc regenerative strategies often employ a scaffold with two distinct regions, one each for the AF and NP. [75][76][77][78][79][80] For instance, Gullbrand et al engineered a 3-part scaffold termed endplatemodified disc-like angle ply structures (eDAPS). 75 ''Endplates'' of porous PCL sandwiched a central portion of a single ''NPregion'' (cell-seeded hyaluronic acid or agarose hydrogel) that was surrounded by multiple concentric ''AF-layers'' (cell-seeded nanofibrous PCL).…”

“…Marshall et al developed a 3D printed, flexible polylactic acid (FPLA) scaffold for whole disc regeneration. 78 By altering printed fiber spacing (i.e., mesh size), the scaffold modulus could be tuned within the range of native whole IVDs. These scaffolds also promoted matrix deposition by NP cells and differentiation of mesenchymal cells towards fibrocartilaginous lineages in vitro.…”

“…Ligorio, 2019 81 Graphene oxide and FEFKFEFK | | Lin, 2019 87 Carboxymethylcellulose-methylcellulose (CMC-MC) | | Marshall, 2021 78 Flexible PLA-alginate 94 High-density collagen (type I) | | Schek, 2011; 88 Cruz, 2018; 89 Hom, 2019; 90 Long, 2020; 91 Panebianco, 2022 92 Fibrin -genipin (+ CMC-MC, 85 86 Type II collagen -chondroitin sulfate | | Zhu, 2017 84 Chitosan -hyaluronic acid | | Table 4 Recent studies utilizing polymer materials for trachea regeneration [96][97][98][99][100][101][102][103][104][105] Study Material Scaffold 3D printed Decellularized Gao, 2017; 96 Gao, 2019 97 PCL | Hong, 2018 100 Rabbit trachea | Hsieh, 2018 101 Biodegradable polyurethanes (PCL diol, polyethylene butylene adipate diol, isophorone diisocyanate, 2,2-bis(hydroxymethyl)propionic acid, ethylenediamine)…”

Nucleus Disc Replacement: Design and Material Selection FEA Analysis

“…In addition, researchers have improved designs continuously to ease insertion. Researchers have recently introduced new materials like nanofbers [28], providing a scafold for cell ingrowth and revitalization [29]. Leading research groups have tested diferent materials [30], and stem cells [31], both autologous and heterologous, are being used, but none of these new strategies have yet reached clinical application.…”