Novel Application of High-Voltage Electrostatic Flocking: Tissue Engineering Scaffolds.

In tissue engineering, scaffolds serve to simulate the authentic in vivo microenvironment, prompting cell differentiation into specific tissues. [24,40,41,80,87] In conventional tissue engineering, porosity and mechanical strength are two conflicting yet equally critical properties. On one hand, scaffolds require a certain degree of porosity to provide ample space for cell migration and integration, facilitate the exchange of nutrients and metabolic waste, and create conditions for the formation of extracellular matrix and capillaries. On the other hand, scaffolds must possess sufficient mechanical strength to withstand the biomechanical loads at the defect site.

[39,40,46,88] Traditional isotropic scaffold materials (such as freeze-dried sponges and porous ceramics) often face the issue of decreased mechanical strength as porosity increases. However, anisotropic scaffolds prepared via electrostatic flocking technology can simultaneously meet the requirements of high porosity and mechanical strength. Furthermore, compared to traditional isotropic scaffolds, electrostatic flocking scaffolds offer significant advantages in meeting the anisotropic demands of human tissues. In short, this technology perfectly combines high porosity with excellent mechanical properties (Figure a) and anisotropic conditions, making it particularly suitable for cartilage tissue engineering, which requires high compressive strength and elasticity (Figure b). [25]

The application of electrostatic flocking technology in tissue engineering began in 2007, when Walther et al. successfully created scaffolds using mineralized collagen as the matrix, gelatin as the adhesive, and polyamide fibers as the network-forming fibers to culture and proliferate mouse 7F2 osteoblasts. [41] This study validated the feasibility of electrostatic flocking scaffolds in cartilage and bone tissue engineering. Compared to polystyrene culture dishes, cells cultured on the scaffolds exhibited higher specific alkaline phosphatase (ALP) activity, particularly after 7 days of culture. This indicates that the three-dimensional cell arrangement on the scaffolds promoted osteogenic differentiation.

[41] Notably, scaffolds with pore sizes in the range of 100-150 μm demonstrated a high porosity of nearly 91%, effectively promoting cell proliferation. [89] Research by the Lien team found that chondrocytes preferentially proliferate and generate extracellular matrix in scaffolds with pore sizes of 250-500 μm. [90] Given that the relative size of round cells typically ranges from 5-20 μm, excessively small pore sizes can hinder cell migration. [91] Scaffolds prepared via electrospinning technology have pore sizes only in the nanometer or low micrometer range, limiting their application in scaffold development.

[24,39,92] In contrast, scaffolds prepared by electrostatic flocking can achieve structures with flexibly adjustable pore sizes, which promote cell migration by forming interconnected pores. Additionally, existing studies have shown that implanting biocompatible degradable fibers into wounds can promote granulation tissue formation, thereby accelerating wound healing. [23,93] The McCarthy team conducted a study on electrostatic flocking scaffolds using chitosan/gelatin (Figure c) as the substrate and polycaprolactone fibers as the flocking layer fibers, applying them to 8 mm full-thickness wounds in type II diabetic mice for 7 and 14 days (Figure d). [6] The results confirmed their efficacy in promoting wound healing. Furthermore, electrostatic flocking scaffolds filled with silver nanoparticles and polycaprolactone fibers demonstrated significantly enhanced cell migration ability and antibacterial activity in vitro experiments. [5]

Currently, there remain numerous unexplored applications of electrostatic flocking technology in tissue engineering. For instance, enhancing the fluffiness of fleece fibers to achieve better granulation effects hinges on selecting suitable absorbable adhesives and high-quality fleece fibers. Additionally, adopting more environmentally friendly fiber processing methods and implementing structures that enhance mechanical properties are crucial steps in optimizing the overall process. Scientists and researchers have conducted preliminary studies in these areas. The McCarthy team used a salt treatment method instead of charge accumulation, ensuring that pinned fibers generate sufficient Coulomb force for upward movement through salt ionization. [6] Notably, the salt in this treatment only adheres to the fiber surface and can be easily removed with water, avoiding any unnecessary negative impact on scaffold application. [6]

Combining two electrostatic flocking scaffolds to form an interlocking structure can enhance mechanical properties through synergy with cells and their secreted extracellular matrix (Figure e). This structure also exhibits higher enhanced cell motility under force (Figure f), [4,94] thereby providing cells with greater protection under external forces.

a) Schematic diagram of an implantable scaffold resisting cellular stress; reproduced with permission. [4] Copyright 2022, Wiley-VCH GmbH.
b) Principle of electrostatic flocking and preparation of cartilage tissue engineering scaffolds; reproduced with permission. [25] Copyright 2021, The Authors. Published by MDPI, Basel, Switzerland.
c) Schematic of surgical strategy: Flocked fibers aligned toward the wound surface, with chitosan/gelatin substrate flush to the wound edges. Splint suturing with adhesive fixation prevents wound contraction; reproduced with permission. [6] Copyright 2021, The Author(s).
d) H&E staining results at 7 and 14 days post-operation for no-treatment group, low-density flocked scaffold group, and high-density flocked scaffold group; reproduced with permission. [6] Copyright 2021, The Author(s).
e) Schematic of the interlocking reinforcement process between scaffold and bone cells; reproduced with permission. [4] Copyright 2022, Wiley-VCH GmbH.
f) Cell viability after 24 hours under static or compression conditions for cells seeded on PLA flocked and electrospun scaffolds; reproduced with permission. [4] Copyright © 2022, Wiley-VCH GmbH.

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