Combined effects of chemical priming and mechanical stimulation on mesenchymal stem cell differentiation on nanofiber scaffolds

Abstract

Functional tissue engineering of connective tissues such as the anterior cruciate ligament (ACL) remains a significant clinical challenge, largely due to the need for mechanically competent scaffold systems for grafting, as well as a reliable cell source for tissue formation. We have designed an aligned, polylactide-co-glycolide (PLGA) nanofiber-based scaffold with physiologically relevant mechanical properties for ligament regeneration. The objective of this study is to identify optimal tissue engineering strategies for fibroblastic induction of human mesenchymal stem cells (hMSC), testing the hypothesis that basic fibroblast growth factor (bFGF) priming coupled with tensile loading will enhance hMSC-mediated ligament regeneration. It was observed that compared to the unloaded, as well as growth factor-primed but unloaded controls, bFGF stimulation followed by physiologically relevant tensile loading enhanced hMSC proliferation, collagen production and subsequent differentiation into ligament fibroblast-like cells, upregulating the expression of types I and III collagen, as well as tenasin-C and tenomodulin. The results of this study suggest that bFGF priming increases cell proliferation, while mechanical stimulation of the hMSCs on the aligned nanofiber scaffold promotes fibroblastic induction of these cells. In addition to demonstrating the potential of nanofiber scaffolds for hMSC-mediated functional ligament tissue engineering, this study yields new insights into the interactive effects of chemical and mechanical stimuli on stem cell differentiation.

Nanoengineered biomaterials for repair and regeneration of orthopedic tissue interfaces

“…[113] The cell-loaded nanofibers were subjected to bFGF treatment and then mechanically stimulated in a bioreactor. The study showed a synergistic effect of mechanical stimulation upon co-stimulation along with the chemical treatment, evidenced by an increase in type I and III collagen, tenascin, and fibronectin expression.…”

“…Although this brief study encourages the use of these nanofibers for ACL treatment, it fails to highlight the bone and transition regions of the scaffold design. [113] A two-spinneret system was developed to fabricate a nanofiber scaffold gradient in another study. [114][115][116] The nanofibers were fabricated from PCL modified with amorphous calcium phosphate nanoparticles (nACP).…”

“…[111,112] PLGA nanofibers with bFGF Aligned PLGA nanofibers Chemical and mechanical stimuli enhanced hMSC proliferation and differentiation respectively. [113] Bone and transition regions of the scaffold were not wellcharacterized. [113] PCL nanofibers with nACP PCL nanofibers Two-spinneret approach for direct nanofiber gradient without additional modification.…”

“…[113] Bone and transition regions of the scaffold were not wellcharacterized. [113] PCL nanofibers with nACP PCL nanofibers Two-spinneret approach for direct nanofiber gradient without additional modification. [116] Scaffold ECM production and mechanical loading were not evaluated.…”

Fiber/collagen composites for ligament tissue engineering: influence of elastic moduli of sparse aligned fibers on mesenchymal stem cells

“…For example, fibroblast growth factor-2 has been shown to enhance the expression of collagen I, III, tenascin-C, and tenomodulin on aligned electrospun meshes. 40 Similarly, growth and differentiation factor-5 has been shown to increase the expression of both Scx and Col 1a1 when adipose derived stem cells are cultured on electrospun scaffolds. 41 Additionally, the release of platelet-derived growth factor from aligned collagen-nanofiber electrospun scaffolds has been shown to enhance the proliferation of adipose derived stem cells and the expression of Scx and tenomodulin.…”