High throughput computational evaluation of how scaffold architecture, material selection, and loading modality influence the cellular micromechanical environment in tissue engineering strategies

Abstract

Background In tissue engineering (TE) strategies, cell processes are regulated by mechanical stimuli. Although TE scaffolds have been developed to replicate tissue‐level mechanical properties, it is intractable to experimentally measure and prescribe the cellular micromechanical environment (CME) generated within these constructs. Accordingly, this study aimed to fill this lack of understanding by modeling the CME in TE scaffolds using the finite element method. Methods A repeating unit of composite fiber scaffold for annulus fibrosus (AF) repair with a fibrin hydrogel matrix was prescribed a series of loading, material, and architectural parameters. The distribution of CME in the scaffold was predicted and compared to proposed target mechanics based on anabolic responses of AF cells. Results The multi‐axial loading modality predicted the greatest percentage of cell volumes falling within the CME target envelope (%PTE) in the study (65 %PTE for 5.0% equibiaxial tensile strain with 50 kPa radial‐direction compression; 7.6 %PTE without radial pressure). Additionally, the architectural scale had a moderate influence on the CME (maximum of 17 %PTE), with minimal change in the tissue‐level properties of the scaffold. Scaffold materials and architectures had secondary influences on the predicted regeneration by modifying the tissue‐level scaffold mechanics. Conclusions Scaffold loading modality was identified as the critical factor for TE the AF. Scaffold materials and architecture were also predicted to modulate the scaffold loading and, therefore, control the CME indirectly. This study facilitated an improved understanding of the relationship between tissue‐level and cell‐level mechanics to drive anabolic cell responses for tissue regeneration.

Regenerating and repairing degenerative intervertebral discs by regulating the micro/nano environment of degenerative bony endplates based on low-tension mechanics

“…However, intervertebral disc cells are sensitive to tensile strength, duration and cycle. AF cells were continuously and periodically pulled (traction) at physiological frequency (1 Hz) and low tension (1%) for more than 24 hours in vitro, which proved that the stability of the internal environment could be maintained [ 52 , 53 ]. Nevertheless, with increased tension (5-18%) and duration (more than 4-6 hours), NP cells responded with increased catabolism (i.e., reduced proteoglycan and upregulation in the expression of NO, Cox2, and MMP3 genes) [ 53 , 54 ].…”

“…AF cells were continuously and periodically pulled (traction) at physiological frequency (1 Hz) and low tension (1%) for more than 24 hours in vitro, which proved that the stability of the internal environment could be maintained [ 52 , 53 ]. Nevertheless, with increased tension (5-18%) and duration (more than 4-6 hours), NP cells responded with increased catabolism (i.e., reduced proteoglycan and upregulation in the expression of NO, Cox2, and MMP3 genes) [ 53 , 54 ]. Similarly, for rabbit NP cells, continuous periodic traction (10%, 0.5 Hz) significantly increased cell proliferation and collagen production within 1-2 days, but this anabolic effect disappeared after 4-8 days [ 55 , 56 ].…”

Biomechanical evaluation of a novel repair strategy for intervertebral disc herniation in an ovine lumbar spine model

“…axial-to-circumferential biaxial stiffness ratio) ( Page and Puttlitz, 2019 ). Further, computational modelling has predicted that increased implant compliance may be beneficial for delivering mechanoregulatory stimulus to resident cells ( Page et al, 1152 ). Microscopic imaging of samples of the multi-scale scaffolds demonstrated that the MEW fibers were retained within the scaffold ( Figure 2 ).…”

“…axialto-circumferential biaxial stiffness ratio) . Further, computational modelling has predicted that increased implant compliance may be beneficial for delivering mechanoregulatory stimulus to resident cells (Page et al, 1152).…”