The Intervertebral Disc

Four fifths of adults in their lives have an experience of back or neck pains, which are often associated with degeneration and injury of the intervertebral disc [132], and about $ 90 billion are needed to treat the intervertebral disc diseases in the United States alone every year [133]. The intervertebral disc (IVD) is a

Multi-layered scaffolds from electrospun and non-electrospun mats and prototype layered electrospun/woven scaffold architecture

Fig. 8.17 Multi-layered scaffolds from electrospun and non-electrospun mats and prototype layered electrospun/woven scaffold architecture. (a) The technique of thermoplastic mats and the incorporation of electrospinning and non-electrospinning. (b) Multi-layered electrospun sheets. (c) Woven polydioxanone textile sandwiched between two electrospun mats. (d) Schematic diagram of the prototype scaffold designed and tested. (e) A cross-sectional view of the layered scaffold. (f) The woven layer. (g) The random electrospun PCL thermoplastic adhesive layer. (h) The aligned PDO electrospun mats. (i) A schematic description of the design rational behind the layered scaffold. Unless specified scale bars are 100 lm (Adapted with permission from Ref. [130]. Copyright 2015 Elsevier Ltd)

cartilaginous tissue that has the abilities in body of separating the spinal vertebrae, permitting a limited range of motion and protecting the spine from impact loading [134]. Degenerative disc disease (DDD) has been associated with aging and is thought to be caused by many factors, including excessive mechanical load, smoking, malnutrition and cell metabolism [135]. Until now, the current treatment is limited to physiotherapy, analgesic therapy, or highly invasive surgical procedures such as spinal fusion, discectomy, or partial or complete removal of damaged IDVs [136, 137]. Surgical procedures are the primary means of addressing severe disc diseases, but their severe invasiveness often leads to tends to limit the flexibility of the spine and accelerate the degeneration of adjacent vertebrae. Tissue-engineered therapy has attracted increasing interest as a solution to traditional strategies, and in particular the use of scaffolds having similar structures to IVDs is expected to regenerate and remodel the IVD tissues. IVD is nonvascular and makes up with two distinct regions, the outer annulus fibrosus (AF) and the inner nucleus pulposus (NP). AF has a complex structure and consists of aligned collagen fibers, whose function is to provide mechanical stability and integrity under bending and torsion loads [138-140], while NP has a gel-like structure and consists of disperse collagen fibers and glucosaminoglycans, both of which are contribute to compressive and shear loads [141]. Thus, the IVD with a structure of proteoglycan hydrogels

The layered scaffold integrated in an in vivo rat model

Fig. 8.18 The layered scaffold integrated in an in vivo rat model. (a) An illustration of the scaffold placement in the rat shoulder. (b-e) Scanning electron micrographs show tissue ingrowth into the layered scaffold after 2 weeks (b), 4 weeks (c), 6 weeks (d) and 12 weeks (e). (f) The capsule size increased up to 2 weeks in vivo, after which it was reduced and better-defined over 12 weeks (Adapted with permission from Ref. [130]. Copyright 2015 Elsevier Ltd)

encapsulated into collagen fibers is much like fiber-reinforced composites. For the IVD plays a key role in the spine mechanics of the body, the idea scaffolds used to repair IVD must have sufficient biomechanical properties and can simulate the characteristics of the two regions.

Ambrosio et al. [142] proposed a PET fiber-reinforced hydrogel Poly(2-hydroxy- ethylmethacrylate)(PHEMA)-PCL composite with high biocompatibility, permeability and hydrophilicity, which has the potential to be used as an artificial disc. Based on the previous studies, due to PCL crystalline microdomains can act as physical crosslinks, the incorporating hydrophobic PCL into PHEMA hydrogels has a good effect in enhancing the compression properties to overcome the lack of mechanical properties of the PHEMA hydrogels in the hydrated state. However, the values of maximum stress and modulus of the PHEMA -PCL composite were significantly lower than those of a canine discs, ranging from 32 to 115 MPa and from 8 to 19 MPa, respectively. When the PHEMA-PCL with semi-interpenetrating networks (s-IPNs) was reinforced by incorporating about 40 vol% PET fiber with winding angles from 45° to 65°. The maximum stress and modulus increased from 12 to 17 MPa and from 30 to 73 MPa, respectively. The trend of compressive stress- strain curve of the reinforced composite system was similar in quality to that of the native disc. When PHEMA/PCL was enhanced with 50 vol% PET fiber with the same winding, the maximum stress and modulus increased up to 20 MPa and

SEM micrograph of (a) a PCL electrospun fiber structure and (b) a PCL-5%Alg composite (1,0009 magnification) (Adapted with permission from Ref. [134]. Copyright 2014 Springer)

Fig. 8.19 SEM micrograph of (a) a PCL electrospun fiber structure and (b) a PCL-5%Alg composite (1,0009 magnification) (Adapted with permission from Ref. [134]. Copyright 2014 Springer)

Images of single phase materials and composites undergoing tensile testing, at the point of failure (Adapted with permission from Ref. [134]. Copyright 2014 Springer)

Fig. 8.20 Images of single phase materials and composites undergoing tensile testing, at the point of failure (Adapted with permission from Ref. [134]. Copyright 2014 Springer)

129 MPa respectively, which were typical values of a canine lumbar IVD. The PET and PCL fiber-reinforced PHEMA composite have the compression properties close to that of canine IVD in different position of the spine. Through controlling the hydrogel matrix and the quantity and winding angle of PET fibers, the hydrophilic- ity and mechanical properties of IVD scaffolds can be adjusted. The composite with semi-IPNs structure can allow for the inward growth of native tissue with the degradation of PCL to leave voids in the network. Although the composites have the mechanical properties similar to canine IVD, they also give good indications for the use of these systems to repair the human IVD.

Strange et al. [134] demonstrated the creation of large 3D electrospun fiber- reinforced hydrogel composites, which could use to achieve a functional engineered IVD scaffold. The thick electrospun PCL fibers with a 3D structure infiltrated into the alginate (Alg) hydrogel to create a PCL-Alg composite, as shown in Fig. 8.19. The mechanical properties of the PCL-Alg composite were strongly affected by their structure based on the dominating responses of individual structural component in indentation and tensile testing. The tensile properties of the PCL-Alg composite were found to be mainly determined by the presence of the electrospun PCL fibers (Fig. 8.20), while the compressive properties were determined by the hydrogel modulus. But it was not clear whether this behavior was caused by the material tensile compression nonlinearity or the structure transverse isotropy. The PCL fibers provided stiffness and strength in tension for the composite, and moderated the time-dependent response in compression at the same time. The gel-phase supported and distributed compressive loads through swelling to tuning the fluid pressurization. The PCL fibers did show a tensile-compressive nonlinearity with varying mechanical properties in the planar and through thickness direction, although they were randomly distributed in the plane. By adjusting the PLC fibers concentration, the nonlinearity of the composite has the potential to match the non-linearity of AF, which consistes of aligned type 1 collagen fibrils [143, 144]. The thick PCL-Alg composite also provides the possibility of preparing a scaffold with comparable thickness to the NP by adjusting the ratio of hydrogel and fibers. This study provides a methodology of designing the tensile and compressive mechanical properties of fiber-reinforced composites by modulating the allocation of fibers and matrix phases to create a tissue-engineered scaffold that is closer to the natural structure of IVD and other tissues.

Thorvaldsson et al. [145] developed a method to combine electrospun PCL nanofibers and aerosol sprayed gelatin gellan gum solution to create a nanofiber- reinforced gellan gum gel scaffold with improved mechanical properties for NP regeneration. When it comes to NP repair, hydrogels have attracted much attention due to their excellent properties. The mechanical stability of hydrogels is usually poor in the case of stretching and compression [146]. To produce electrospun nanofiber-reinforced hydrogels with improve structural integrity and mechanical properties, the gellan gum solution was sprayed onto a mandrel rotating in a calcium chloride bath to produce a hydrogel, while, at the same time, the PCL nanofibers were electrospinning to the same collector to enhance the hydrogel. The incorporation of gellan gum concentration, nanofibers and crosslinker concentration could be applied to adjust the mechanical properties of the material based on optical and rheological evaluation results. Furthermore, the composite was enhanced by adding only a small amount of nanofibers. And their reinforcing effects could be changed by tuning the amount of fibers alone. The incorporation of a small amount of nanofibers allowed the hydrogel scaffold to have rheological properties similar to those of human NP, and the resulting modulus were within the range of previously reported natural human NPs. The study shows the flexibility and potential of the nanofiber-reinforced gel with suitable properties used for NP tissue engineering.

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