Isotropic and Anisotropic Scaffolds for Tissue Engineering: Collagen, Conventional, and Textile Fabrication Technologies and Properties.

In this review article, tissue engineering and regenerative medicine are briefly explained and the importance of scaffolds is highlighted. Furthermore, the requirements of scaffolds and how they can be fulfilled by using specific biomaterials and fabrication methods are presented. Detailed insight is given into the two biopolymers chitosan and collagen. The fabrication methods are divided into two categories: isotropic and anisotropic scaffold fabrication methods. Processable biomaterials and achievable pore sizes are assigned to each method. In addition, fiber spinning methods and textile fabrication methods used to produce anisotropic scaffolds are described in detail and the advantages of anisotropic scaffolds for tissue engineering and regenerative medicine are highlighted.

Anisotropic Chitosan Scaffolds Generated by Electrostatic Flocking Combined with Alginate Hydrogel Support Chondrogenic Differentiation.

The replacement of damaged or degenerated articular cartilage tissue remains a challenge, as this non-vascularized tissue has a very limited self-healing capacity. Therefore, tissue engineering (TE) of cartilage is a promising treatment option. Although significant progress has been made in recent years, there is still a lack of scaffolds that ensure the formation of functional cartilage tissue while meeting the mechanical requirements for chondrogenic TE. In this article, we report the application of flock technology, a common process in the modern textile industry, to produce flock scaffolds made of chitosan (a biodegradable and biocompatible biopolymer) for chondrogenic TE. By combining an alginate hydrogel with a chitosan flock scaffold (CFS+ALG), a fiber-reinforced hydrogel with anisotropic properties was developed to support chondrogenic differentiation of embedded human chondrocytes. Pure alginate hydrogels (ALG) and pure chitosan flock scaffolds (CFS) were studied as controls. Morphology of primary human chondrocytes analyzed by cLSM and SEM showed a round, chondrogenic phenotype in CFS+ALG and ALG after 21 days of differentiation, whereas chondrocytes on CFS formed spheroids. The compressive strength of CFS+ALG was higher than the compressive strength of ALG and CFS alone. Chondrocytes embedded in CFS+ALG showed gene expression of chondrogenic markers (COL II, COMP, ACAN), the highest collagen II/I ratio, and production of the typical extracellular matrix such as sGAG and collagen II. The combination of alginate hydrogel with chitosan flock scaffolds resulted in a scaffold with anisotropic structure, good mechanical properties, elasticity, and porosity that supported chondrogenic differentiation of inserted human chondrocytes and expression of chondrogenic markers and typical extracellular matrix.

Influence of Spinning Method on Shape Memory Effect of Thermoplastic Polyurethane Yarns.

Shape memory polymers are gaining increasing attention, especially in the medical field, due to their ability to recover high deformations, low activation temperatures, and relatively high actuation stress. Furthermore, shape memory polymers can be applied as fiber-based solutions for the development of smart devices used in many fields, e.g., industry 4.0, medicine, and skill learning. These kind of applications require sensors, actors, and conductive structures. Textile structures address these applications by meeting requirements such as being flexible, adaptable, and wearable. In this work, the influence of spinning methods and parameters on the effect of shape memory polymer yarns was investigated, comparing melt and wet spinning. It is shown that the spinning method can significantly influence the strain fixation and generated stress during the activation of the shape memory effect. Furthermore, for wet spinning, the draw ratio could affect the stress conversion, influencing its efficiency. Therefore, the selection of the spinning process is essential for the setting of application-specific shape-changing properties.

Thermoresponsive Shape Memory Fibers for Compression Garments.

Their highly deformable properties make shape memory polymers (SMP) a promising component for the development of new compression garments. The shape memory effect (SME) can be observed when two polymers are combined. In here, polycaprolactone (PCL) and thermoplastic polyurethane (TPU) were melt spun in different arrangement types (blend, core-sheath, and island-in-sea), whereas the best SME was observed for the blend type. In order to trigger the SME, this yarn was stimulated at a temperature of 50 °C. It showed a strain fixation of 62%, a strain recovery of 99%, and a recovery stress of 2.7 MPa.

Collagen multifilament spinning.

The benefits of fiber based implants and scaffolds for tissue engineering applications are their anisotropic, highly porous, and controllable macro-, micro-, and nanostructure. Collagen is one of the most commonly used material for the fabrication of scaffolds, as this biopolymer is present in the natural extracellular matrix. For textile processing and textile scaffold fabrication methods, multifilament yarns are required, however, only monofilaments can be generated by state-of-the-art collagen spinning. Hence, the research presented in here aimed at the development of a collagen multifilament wet-spinning process in reproducible quality as well as the characterization of non-crosslinked and crosslinked wet-spun multifilament yarns. Wet spun collagen yarns were comprised of 6 single filaments each having a fineness of 5 tex and a diameter of 80 µm. The tensile strength of the glutaraldehyde crosslinked yarns was 169 MPa (Young's modulus 3534 MPa) in the dry state and 40 MPa (Young's modulus 281 MPa) in the wet state. Furthermore, wet spun collagen filaments showed a characteristic fibrillar structure, which was similar the morphological structure of natural collagen fibers. The textile processing of collagen multifilament yarn was demonstrated by means of knitting technology.

Wet spinning and riboflavin crosslinking of collagen type I/III filaments.

Reconstituted fibrillary collagen is one of the most advantageous biomaterials for biomedical applications. The objective of the research project described in this paper was to evaluate whether riboflavin-induced photo-crosslinking could be used as a non-toxic alternative to glutaraldehyde (GA)-crosslinking for the preparation of wet spun collagen filaments. Collagen filaments were produced on a laboratory wet spinning line and crosslinked with GA or riboflavin with and without UV exposure. Based on mechanical and thermal analyses, it was concluded that the combination of riboflavin and UV light leads to crosslinked collagen filaments having improved mechanical and thermal properties. Furthermore, riboflavin-crosslinked filaments exhibited a higher cytocompatibility for human mesenchymal stem cells compared to GA-crosslinked filaments.

Electrostatic flocking of chitosan fibres leads to highly porous, elastic and fully biodegradable anisotropic scaffolds.

UNLABELLED: Electrostatic flocking - a common textile technology which has been applied in industry for decades - is based on the deposition of short polymer fibres in a parallel aligned fashion on flat or curved substrates, covered with a layer of a suitable adhesive. Due to their highly anisotropic properties the resulting velvet-like structures can be utilised as scaffolds for tissue engineering applications in which the space between the fibres can be defined as pores. In the present study we have developed a fully resorbable compression elastic flock scaffold from a single material system based on chitosan. The fibres and the resulting scaffolds were analysed concerning their structural and mechanical properties and the biocompatibility was tested in vitro. The tensile strength and Young's modulus of the chitosan fibres were analysed as a function of the applied sterilisation technique (ethanol, supercritical carbon dioxide, γ-irradiation and autoclaving). All sterilisation methods decreased the Young's modulus (from 14GPa to 6-12GPa). The tensile strength was decreased after all treatments - except after the autoclaving of chitosan fibres submerged in water. Compressive strength of the highly porous flock scaffolds was 18±6kPa with a elastic modulus in the range of 50-100kPa. The flocked scaffolds did not show any cytotoxic effect during indirect or direct culture of human mesenchymal stem cells or the sarcoma osteogenic cell line Saos-2. Furthermore cell adhesion and proliferation of both cell types could be observed. This is the first demonstration of a fully biodegradable scaffold manufactured by electrostatic flocking. STATEMENT OF SIGNIFICANCE: Most tissues possess anisotropic fibrous structures. In contrast, most of the commonly used scaffolds have an isotropic morphology. By utilising the textile technology of electrostatic flocking, highly porous and clearly anisotropic scaffolds can be manufactured. Flocking leads to parallel aligned short fibres, glued on the surface of a substrate. Such structures are characterised by a high and adjustable porosity, accompanied by distinct stiffness in fibre direction. The present article describes for the first time a fully biodegradable flock scaffold, solely made of chitosan. Utilisation of only one material for manufacturing of flock substrate, adhesive and fibres allow a uniform degradation of the whole construct. Such a new type of scaffold can be of great interest for a variety of biomedical applications.