Dynamic Tensile Loading Improves the Functional Properties of Mesenchymal Stem Cell-Laden Nanofiber-Based Fibrocartilage

Abstract

Fibrocartilaginous tissues such as the meniscus serve critical load-bearing roles, relying on arrays of collagen fibers to resist tensile loads experienced with normal activity. As these structures are frequently injured and possess limited healing capacity, there exists great demand for tissue-engineered replacements. Toward recreating the structural features of these anisotropic tissues in vitro, we employ scaffolds composed of co-aligned nanofibers that direct mesenchymal stem cell (MSC) orientation and the formation of organized extracellular matrix (ECM). Concomitant with ECM synthesis, the mechanical properties of constructs increase with freeswelling culture, but ultimately failed to achieve equivalence with meniscal fibrocartilage. As mechanical forces are essential to the development and maintenance of musculoskeletal tissues, this work examined the effect of cyclic tensile loading on MSC-laden nanofibrous constructs. We hypothesized that loading would modulate the transcriptional behavior of MSCs, spur the deposition of ECM, and lead to enhancements in construct mechanical properties compared to free-swelling controls. Fiber-aligned scaffolds were seeded with MSCs and dynamically loaded daily in tension or maintained as nonloaded controls for 4 weeks. With mechanical stimulation, fibrous gene expression increased, collagen deposition increased, and the tensile modulus increased by 16% relative to controls. These results show that dynamic tensile loading enhances the maturation of MSC-laden aligned nanofibrous constructs, suggesting that recapitulation of the structural and mechanical environment of load-bearing tissues results in increases in functional properties that can be exploited for tissue engineering applications.

Repair of dense connective tissues via biomaterial-mediated matrix reprogramming of the wound interface

“…For example, delivery of TGF-β could enhance matrix synthesis [35], while lysyl oxidase could stabilize the wound interface by promoting collagen crosslinking [30]. On the tissue level, controlled resumption of load bearing activity, engendering both tensile and compressive loading, could promote development of native tissue architecture [36, 37]. Since 3D migration depends on deformation and contraction-mediated movement through tight interstitia, cell mechanics and contractility pathways might also be manipulated to enhance mobility [11, 38] and thereby improve endogenous tissue repair.…”

Biaxial mechanics and inter‐lamellar shearing of stem‐cell seeded electrospun angle‐ply laminates for annulus fibrosus tissue engineering

“…In the future, multi-polymer scaffolds could be used to increase porosity and accelerate cell infiltration, allowing for increased and more homogeneous matrix deposition. 32,37 It is likely that with further cell infiltration, construct maturation or mechanically accelerated growth, 38 native tissue properties and nonlinearity may be more closely replicated.…”

Unravelling the Role of Mechanical Stimuli in Regulating Cell Fate During Osteochondral Defect Repair

“…In this case the parameter ε fibrocartilage was varied between 10 %, 12.5 % and 15 % strain. As an additional part of this study, based on reports that dynamic tensile strain is required to promote fibrocartilage formation [18][19][20] , alternative measures of strain were again examined (See Supplementary Material: Section 8.4). …”

“…These findings suggest that mechanics plays a key role in regulating hypertrophy and endochondral ossification of cartilage. In addition, numerous in vitro studies have shown that MSCs exposed to high magnitudes of dynamic tensile strain, when maintained in chondrogenic media, display markers of fibrocartilage [18][19][20] .…”