Enhancing the Biomechanical Performance of Anisotropic Nanofibrous Scaffolds in Tendon Tissue Engineering: Reinforcement with Cellulose Nanocrystals

Abstract

Anisotropically aligned electrospun nanofibrous scaffolds based on natural/synthetic polymer blends have been established as a reasonable compromise between biological and biomechanical performance for tendon tissue engineering (TE) strategies. However, the limited tensile properties of these biomaterials restrict their application in this field due to the load-bearing nature of tendon/ligament tissues. Herein, the use of cellulose nanocrystals (CNCs) as reinforcing nanofillers in aligned electrospun scaffolds based on a natural/synthetic polymer blend matrix, poly-ε-caprolactone/chitosan (PCL/CHT) is reported. The incorporation of small amounts of CNCs (up to 3 wt%) into tendon mimetic nanofiber bundles has a remarkable biomaterial-toughing effect (85% ± 5%, p < 0.0002) and raises the scaffolds mechanical properties to tendon/ligament relevant range (σ = 39.3 ± 1.9 MPa and E = 540.5 ± 83.7 MPa, p < 0.0001). Aligned PCL/CHT/CNC nanocomposite fibrous scaffolds meet not only the mechanical requirements for tendon TE applications but also provide tendon mimetic extracellular matrix (ECM) topographic cues, a key feature for maintaining tendon cell's morphology and behavior. The strategy proposed here may be extended to other anisotropic aligned nanofibrous scaffolds based on natural/synthetic polymer blends and enable the full exploitation of the advantages provided by their tendon mimetic fibrous structures in tendon TE.

Fibre-based scaffolding techniques for tendon tissue engineering

“…In a recent study, Domingues et al () incorporated cellulose nanocrystals (CNCs) into electrospun nanofibre scaffolds using distinct ratios of CNCs (1%, 3%, and 6%) on the basis of a polymer blend of PCL and chitosan. A remarkable biomaterial‐toughing effect was observed due to the inclusion of CNC, and the scaffolds mechanical properties were enhanced to match the native tendon properties with modulus of 540 MPa and tensile stress of 40 MPa.…”

“…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).…”

Biodegradable polymer nanocomposites for ligament/tendon tissue engineering

“…However, its hydrophobicity may results in poor cell attachment and proliferation [81]. For that reason, when aiming tendon/ligament regeneration, PCL and derivatives are usually combined with other polymers such as CHI [82,83], or simply coated with Col [80,84]. In a study, electrospun PCL fibers were implanted in a rodent model for wound healing, showing evidences that PCL is nonimmunogenic, being integrated into local tissue without adverse reactions [85].…”

“…However, their quick degradability and low-mechanical properties may limit their application in tissue engineering, while synthetic polymers present low bioactivity and higher mechanical properties [37]. Thus, the combination both types of materials is expected to yield a synergetic effect between natural and synthetic polymers [37], and has been proposed as a good compromise between biological and mechanical performance for tendon and ligament regeneration [83,104].…”

Heterogeneity of Scaffold Biomaterials in Tissue Engineering

“…Anisotropic cellulose nanofillers augment mechanical strength of ECM scaffolds allowing for bioengineering of load-bearing tissues, specifically tendons and ligaments [51]. Cellulose also lends itself well to the more rigid tissues of the human body such as bone, cartilage, and cardiac tissues [52,53,54].…”