Advanced Nanofiber-Based Scaffolds for Achilles Tendon Regenerative Engineering

Abstract

The Achilles tendon (AT) is responsible for running, jumping, and standing. The AT injuries are very common in the population. In the adult population (21-60 years), the incidence of AT injuries is approximately 2.35 per 1,000 people. It negatively impacts people's quality of life and increases the medical burden. Due to its low cellularity and vascular deficiency, AT has a poor healing ability. Therefore, AT injury healing has attracted a lot of attention from researchers. Current AT injury treatment options cannot effectively restore the mechanical structure and function of AT, which promotes the development of AT regenerative tissue engineering. Various nanofiber-based scaffolds are currently being explored due to their structural similarity to natural tendon and their ability to promote tissue regeneration. This review discusses current methods of AT regeneration, recent advances in the fabrication and enhancement of nanofiber-based scaffolds, and the development and use of multiscale nanofiber-based scaffolds for AT regeneration.

Keywords: Achilles tendon; nanofiber technology; nanofibers; regenerative engineering; scaffolds.

FIGURE 1

Graded arrangement of the collagen of tendons: (A) SEM image of epitenon fibrils (scale = 2 microns); (B) SEM image of secondary fiber bundle (scale = 100 micron); (C) SEM images of primary fiber bundle (scale = 45 microns); and (D) SEM image of collagen fibrils (scale = 1.8 micron). Permission to reproduce was granted under the conditions of the license (CC BY 4.0). Copyright 2018, Sensini et al.

FIGURE 2

Typical tendon stress and strain curves and a schematic diagram of collagen fiber behavior. Four diverse regions may be observed. (1) Toe region (<2% strain), where fibers are crimped; (2) linear region (2%–6% strain), where fibers are straightened; (3) yield region (6%–8% strain), when microscopic failure is produced; and (4) failure region (>8% strain), where rupture is produced. (1) and (2) regions are regarded as physiological range, as previously described (Ruiz-Alonso et al., 2021).

FIGURE 3

Schematization representation of the nanofiber manufacturing technology. (A) Self-assembly. Permission to reproduce was granted under the conditions of the license (CC BY 4.0). Copyright 2019, Nemati et al. (2019). (B) Thermal phase separation for the preparation of anisotropic polyurethane porous nano-scaffolds. Permission to reproduce was granted under the conditions of the license (CC BY 4.0). Copyright 2018, Zeinali et al. (2021). (C) Electrospinning. Permission to reproduce was granted under the conditions of the license (CC BY 4.0). Copyright 2019, Nemati et al. (2019).

FIGURE 4

Multiscale nanofibrous textile-based scaffolds for the regeneration of AT regeneration. (A) Knit. Permission to reproduce was granted under the conditions of the license (CC BY 4.0). Copyright 2021, Ayodele et al. (2021) (B) Braid. Permission to reproduce was granted under the conditions of the license (CC BY 4.0). Copyright 2019, Ding et al. (2019) (C) Woven. Permission to reproduce was granted under the conditions of the license (CC BY 4.0). Copyright 2021, Yun et al. (2021).

FIGURE 5

(A) Figure shows the different layers in the electrospinning patch. The electrospinning assembly of the patch consists of seven layers of aligned electrospun PDO fibers sandwiched alternately between 6 layers of thin PCL electrospinning mesh (used as a binder). A single layer of aligned electrospinning PCL fibers is used to join the electrospun components with a braided PDO monofilament layer. (B) Patch sample photo displays the white electrospun PDO layer (facing the tendon) and the blue woven PDO layer. (C–E) Typical SEM images showing the electrospinning layer. (F–H) Figures show woven patch layers at various magnifications. Permission to reproduce was granted under the conditions of the license (CC BY 4.0). Copyright 2020, Rashid et al. (2020).