Engineering controllable anisotropy in electrospun biodegradable nanofibrous scaffolds for musculoskeletal tissue engineering

Abstract

Many musculoskeletal tissues exhibit significant anisotropic mechanical properties reflective of a highly oriented underlying extracellular matrix. For tissue engineering, recreating this organization of the native tissue remains a challenge. To address this issue, this study explored the fabrication of biodegradable nanofibrous scaffolds composed of aligned fibers via electrospinning onto a rotating target, and characterized their mechanical anisotropy as a function of the production parameters. The characterization showed that nanofiber organization was dependent on the rotation speed of the target; randomly oriented fibers (33% fiber alignment) were produced on a stationary shaft, whereas highly oriented fibers (94% fiber alignment) were produced when rotation speed was increased to 9.3 m/sec. Non-aligned scaffolds had an isotropic tensile modulus of 2.1 ± 0.4 MPa, compared to highly anisotropic scaffolds whose modulus was 11.6 ± 3.1 MPa in the presumed fiber direction, suggesting that fiber alignment has a profound effect on the mechanical properties of scaffolds. Mechanical anisotropy was most pronounced at higher rotation speeds, with a greater than 33-fold enhancement of the Young's modulus in the fiber direction compared to perpendicular to the fiber direction at a rotation speed reached 8 m/sec. In cell culture, both the organization of actin filaments of human mesenchymal stem cells and the cellular alignment of meniscal fibroblasts were dictated ‡Corresponding Author: Rocky S. Tuan, Ph. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. by the prevailing nanofiber orientation. This study demonstrates that controllable and anisotropic mechanical properties of nanofibrous scaffolds can be achieved by dictating nanofiber organization through intelligent scaffold design. NIH Public Access

The Effect of Rotating Collector Design on Tensile Properties and Morphology of Electrospun Polycaprolactone Fibres

“…Previous studies suggested that cells appeared to favour a fibrous scaffold with a higher degree of alignment, in terms of cell alignment, proliferation, and extracellular matrix production [11,16]. However, less aligned fibre exhibited larger pore sizes, resulting in a higher number of cells attached, although in the longer term (7 and 14 days) the difference was not significant [16].…”

“…It is also confirmed by other studies. Electrospinning using different mandrel rotation speeds (0 -8 m/s) showed that higher speeds produce fibres with higher alignment and tensile moduli, but yield lower ultimate strains [11]. One possible explanation is that it was due to fibre engagement at the beginning of deformation.…”

“…Tissues in musculoskletal system exhibit specific fibre alignment, mainly those that function as load bearing structures [11,12]. This system includes fibrocartilage, a connective tissue located in the joints, for instance glenoid labrum in shoulder, acetabular labrum in hip, annulus fibrossus in intervertebral joint, and meniscus in knee, as well as tendons and ligaments [13][14][15].…”

Chondrogenic Differentiation of Human Mesenchymal Stem Cells on Oriented Nanofibrous Scaffolds: Engineering the Superficial Zone of Articular Cartilage

“…14 The present study is therefore focused on engineering a tissue-like construct that will mimic the superficial zone of articular cartilage using bone marrow-derived human mesenchymal stem cells (hMSCs) and electrospun biocompatible polycaprolactone (PCL) scaffolds. Although several studies have been published to demonstrate that hMSCs or chondrocytes can be cultured on oriented electrospun nanofibrous scaffolds, 17,18 attempts to specifically engineer the superficial zone of the articular cartilage are currently lacking. Here we report that alignment and chondrogenic differentiation of hMSCs cultured on oriented electrospun PCL scaffolds are feasible and relatively easy to implement.…”

Innovative Strategies for Treatment of Soft Tissue Injuries in Human and Animal Athletes

“…Yet another challenge resides in the fact that a functional meniscal tissue must exhibit notable anisotropic mechanical properties resulting from a highly oriented underlying extracellular matrix [1]. In order to generate a scaffold which has controllable, anisotropic properties and mimicks meniscal extracellular matrix fiber alignment to direct fibrochondrocyte orientation electrospinning technology was used [25]. This technique is based on a biodegradable polymer and results in cartilage with about 20 % of the strength of native cartilage but with quite small pores that are difficult for chondrocytes to penetrate [3].…”