A dual-phase scaffold produced by rotary jet spinning and electrospinning for tendon tissue engineering

Tendon is a highly hierarchical and oriented tissue that provides high mechanical strength. Tendon injuries lead to loss of function, disability, and a decrease in quality of life. The limited healing capacity of tendon tissue leads to scar tissue formation, which can affect mechanical strength and cause a re-tear. Tissue engineering can be the solution to achieving complete and proper healing of tendon. The developed constructs should be mechanically strong while maintaining a suitable environment for cell proliferation. In this study, a dual-phase fibrous scaffold was produced by combining fibrous mats produced by rotary jet spinning (RJS) and wet electrospinning (WES), with the intent of improving the healing capacity of the construct. Dual-phase scaffolds were formed from aligned poly(ϵ-caprolactone) (PCL) fibers (Shell) produced by RJS and randomly oriented PCL or PCL/gelatin fibers (Core) produced by WES systems. The scaffolds mimicked i) the repair phase of tendon healing, in which randomly-oriented collagen type III is deposited by randomly-oriented WES fibers and ii) the remodeling stage, in which aligned collagen type I fibers are deposited by aligned RJS fibers. In vitro studies showed that the presence of randomly-oriented core fibers inside the aligned PCL fiber shell of the dual-phase scaffold increased the initial attachment and viability of cells. Scanning electron microscopy and confocal microscopy analysis showed that the presence of aligned RJS fibers supported the elongation of cells through aligned fibers which improves tendon tissue healing by guiding oriented cell proliferation and extracellular matrix deposition. Tenogenic differentiation of human adipose-derived mesenchymal stem cells on scaffolds was studied when supplemented with growth differentiation factor 5 (GDF-5). GDF-5 treatment improved the viability, collagen type III deposition and scaffold penetration of human adipose derived stem cells. The developed FSPCL/ESPCL-Gel 3:1 scaffold (FS = centrifugal force spinning/RJS, ES = wet electrospinning, Gel = gelatin) sustained high mechanical strength, and improved cell viability and orientation while supporting tenogenic differentiation.