Alignment of collagen fiber in knitted silk scaffold for functional massive rotator cuff repair

Abstract

a b s t r a c tRotator cuff tear is one of the most common types of shoulder injuries, often resulting in pain and physical debilitation. Allogeneic tendon-derived decellularized matrices do not have appropriate pore size and porosity to facilitate cell infiltration, while commercially-available synthetic scaffolds are often inadequate at inducing tenogenic differentiation. The aim of this study is to develop an advanced 3D aligned collagen/silk scaffold (ACS) and investigate its efficacy in a rabbit massive rotator cuff tear model. ACS has similar 3D alignment of collagen fibers as natural tendon with superior mechanical characteristics. Based on ectopic transplantation studies, the optimal collagen concentration (10 mg/ml), pore diameter (108.43 ± 7.25 lm) and porosity (97.94 ± 0.08%) required for sustaining a stable macro-structure conducive for cellular infiltration was determined. Within in vitro culture, tendon stem/progenitor cells (TSPCs) displayed spindle-shaped morphology, and were well-aligned on ACS as early as 24 h. TSPCs formed intercellular contacts and deposited extracellular matrix after 7 days. With the in vivo rotator cuff repair model, the regenerative tendon of the ACS group displayed more conspicuous native microstructures with larger diameter collagen fibrils (48.72 ± 3.75 vs. 44.26 ± 5.03 nm) that had better alignment and mechanical properties (139.85 ± 49.36 vs. 99.09 ± 33.98 N) at 12 weeks post-implantation. In conclusion, these findings demonstrate the positive efficacy of the macroporous 3D aligned scaffold in facilitating rotator cuff tendon regeneration, and its practical applications for rotator cuff tendon tissue engineering. Statement of SignificanceMassive rotator cuff tear is one of the most common shoulder injuries, and poses a formidable clinical challenge to the orthopedic surgeon. Tissue engineering of tendon can potentially overcome the problem. However, more efficacious scaffolds with good biocompatibility, appropriate pore size, favorable inductivity and sufficient mechanical strength for repairing massive rotator cuff tendon injuries need to be developed. In this study, we developed a novel macroporous 3D aligned collagen/silk scaffold, and demonstrated that this novel scaffold enhanced the efficacy of rotator cuff tendon regeneration by inducing aligned supracellular structures similar to natural tendon, which in turn enhanced http://dx

Fibre-based scaffolding techniques for tendon tissue engineering

“…In the most recent study, Zheng et al () fabricated a 3D aligned collagen/silk scaffold (ACS). The collagen was oriented using a unidirectional freezing technique, in which the collagen was frozen from one end to another gradually, and surrounded the knitted scaffold.…”

“…In order to make up for the limitations of a single material, (Czaplewski et al, 2014;Rothrauff et al, 2017), collagen-silk (Chen et al, 2008;Zheng et al, 2017), PCL-chitosan (Domingues et al, 2016;Zhao et al, 2015), PCL-gelatin (Yang, Lin, Rothrauff, Yu, & Tuan, 2016), and PLGA-silk (Sahoo, Ouyang, Goh, Tay, & Toh, 2006).…”

“…In the most recent study, Zheng et al (2017) Apart from the adequate mechanical properties and ease of building 3D geometries, knitted scaffolds are able to adjust its physical and mechanical properties by varying the pore size, which makes it attractive to construct porous tissues. However, knitted scaffold was reported to require gel systems for cell seeding (e.g., fibrin or collagen gel), which declined the pore size (Sahoo et al, 2006).…”

Biodegradable polymer nanocomposites for ligament/tendon tissue engineering

“…Scaffolds have been produced using collagen and sericinextracted silk to improve scaffold properties for tendon/ ligament applications and then seeded with cells [1,[98][99][100][101][102]. Chen et al [54,98] embedded MSCs derived from human embryonic stem cells within a knitted silk-Col sponge scaffold and achieved an enhancement of tendon tissue regeneration.…”

A bench‐top molding method for the production of cell‐laden fibrin micro‐fibers with longitudinal topography

“…Many native tissues, such as muscle and tendon, are composed of aligned fibers, making TE fibers a logical building block for the reconstruction of such tissues. Particularly interesting bottom‐up applications of TE fibers includes bio‐weaving and biotextiles (Akbari et al, ; Zheng et al, ). By weaving and patterning using classical textile methods, TE fibers can be assembled to create constructs that mimic fibrous native tissues, as well as non‐fibrous tissues and organs (Onoe et al, ).…”