Impact of Electrospun Piezoelectric Core–Shell PVDFhfp/PDMS Mesh on Tenogenic and Inflammatory Gene Expression in Human Adipose-Derived Stem Cells: Comparison of Static Cultivation with Uniaxial Cyclic Tensile Stretching

Abstract

Specific microenvironments can trigger stem cell tenogenic differentiation, such as specific substrates or dynamic cell cultivation. Electrospun meshes composed by core–shell fibers (random or aligned; PDMS core; piezoelectric PVDFhfp shell) were fabricated by coaxial electrospinning. Elastic modulus and residual strain were assessed. Human ASCs were seeded on such scaffolds either under static conditions for 1 week or with subsequent 10% dynamic stretching for 10,800 cycles (1 Hz, 3 h), assessing load elongation curves in a Bose® bioreactor system. Gene expression for tenogenic expression, extracellular matrix, remodeling, pro-fibrotic and inflammatory marker genes were assessed (PCR). For cell-seeded meshes, the E modulus increased from 14 ± 3.8 MPa to 31 ± 17 MPa within 3 h, which was not observed for cell-free meshes. Random fibers resulted in higher tenogenic commitment than aligned fibers. Dynamic cultivation significantly enhanced pro-inflammatory markers. Compared to ASCs in culture flasks, ASCs on random meshes under static cultivation showed a significant upregulation of Mohawk, Tenascin-C and Tenomodulin. The tenogenic commitment expressed by human ASCs in contact with random PVDFhfp/PDMS paves the way for using this novel highly elastic material as an implant to be wrapped around a lacerated tendon, envisioned as a functional anti-adhesion membrane.

Unlocking the Potential of Stem Cell Microenvironments In Vitro

“…These findings demonstrate the potential of combining myogenic progenitors and biomaterials for engineering functional skeletal muscle grafts and advancing the field of muscle tissue engineering. In a similar fashion, Baumgartner et al took advantage of coaxial electrospinning to generate meshes of fibers with different orientations and replicate the mechanical properties of tendons [ 77 ]. Human adipose-derived stem cells were seeded on the fibers and subjected to various stretching conditions.…”

Advances in mesenchymal stem cells therapy for tendinopathies

“… 30 , 31 Secondary tendon tissue damage is another important cause of tendinopathy and includes degeneration of tendon fibers due to long-term smoking and alcohol abuse; degeneration of tendons due to long-term glucocorticoid use; and degeneration of tendons due to excessive passive stretching of the tendon causing damage to small blood vessels or inadequate diffusion of nutrients within the tendon. 32 These causes can be explained by the second view ( Fig. 1 ) and the apoptotic, vascular, neurological, and continuous model theory, where smoking, alcohol abuse, hormones, and hypoxia all affect the cellular microenvironment, reducing cell-cell matrix and cell-cell interaction, disrupting extracellular matrix synthesis, triggering apoptosis in tendon cells and impeding collagen fiber production.…”

Functional biomaterials for tendon/ligament repair and regeneration

“…In addition to the innovation of the electrostatic spinning material itself, the way it is secured at the wound site has an equally profound impact on wound healing. As electrospun nanofibers can slip under external forces, thus hindering the proliferation and differentiation of migrating stem cells, Wang offers a new way of thinking about how to anchor them more firmly and improve their ability to promote tissue regeneration [ 122 ]. Poly(ester-urethane) urea and gelatin were electrospun and double crosslinked by a multi-bonding network densification strategy to create nanofiber scaffolds with formed joints to mimic the natural microstructure of tendon-to-bone insertion.…”