Passive Strain-Induced Matrix Synthesis and Organization in Shape-Specific, Cartilaginous Neotissues

Abstract

Tissue-engineered musculoskeletal soft tissues typically lack the appropriate mechanical robustness of their native counterparts, hindering their clinical applicability. With structure and function being intimately linked, efforts to capture the anatomical shape and matrix organization of native tissues are imperative to engineer functionally robust and anisotropic tissues capable of withstanding the biomechanically complex in vivo joint environment. The present study sought to tailor the use of passive axial compressive loading to drive matrix synthesis and reorganization within self-assembled, shape-specific fibrocartilaginous constructs, with the goal of developing functionally anisotropic neotissues. Specifically, shape-specific fibrocartilaginous neotissues were subjected to 0, 0.01, 0.05, or 0.1 N axial loads early during tissue culture. Results found the 0.1-N load to significantly increase both collagen and glycosaminoglycan synthesis by 27% and 67%, respectively, and to concurrently reorganize the matrix by promoting greater matrix alignment, compaction, and collagen crosslinking compared with all other loading levels. These structural enhancements translated into improved functional properties, with the 0.1-N load significantly increasing both the relaxation modulus and Young's modulus by 96% and 255%, respectively, over controls. Finite element analysis further revealed the 0.1-N uniaxial load to induce multiaxial tensile and compressive strain gradients within the shape-specific neotissues, with maxima of 10.1%, 18.3%, and -21.8% in the XX-, YY-, and ZZ-directions, respectively. This indicates that strains created in different directions in response to a single axis load drove the observed anisotropic functional properties. Together, results of this study suggest that strain thresholds exist within each axis to promote matrix synthesis, alignment, and compaction within the shape-specific neotissues. Tailoring of passive axial loading, thus, presents as a simple, yet effective way to drive in vitro matrix development in shape-specific neotissues toward more closely achieving native structural and functional properties.

Fabrication of anatomically-shaped cartilage constructs using decellularized cartilage-derived matrix scaffolds

“…6). Dynamic loading during in vitro culture has been shown to promote collagen alignment that mimics the structural and functional properties of the native tissue [74, 75], and could ameliorate the lack of organization observed in the current study. Together, these findings demonstrated that the decellularized CDM retained its chondroinductive capacity and ability to prevent a hypertrophic phenotype in MSCs; however, further work is needed to achieve hierarchical organization of the newly synthesized tissue.…”

A Guide for Using Mechanical Stimulation to Enhance Tissue-Engineered Articular Cartilage Properties

“…Fibrocartilage derived from meniscus and articular chondrocyte cocultures also yielded a 27% increase in collagen content when stimulated passively with a 0.1 N DC load. 72 Although collagen II content specifically needs to be investigated more thoroughly, these studies show that DC is a potent regimen for increasing total collagen content.…”

Temporomandibular Joint Regenerative Medicine

“…Their implantation evidenced positive results. Significant improvement of regeneration was observed with the spatiotemporal gradient of functionalization [ 176 ]. Same approaches were developed to engineer human 3D-printed TMJ discs.…”