3D Printing and Electrospinning of Composite Hydrogels for Cartilage and Bone Tissue Engineering

Abstract

Injuries of bone and cartilage constitute important health issues costing the National Health Service billions of pounds annually, in the UK only. Moreover, these damages can become cause of disability and loss of function for the patients with associated social costs and diminished quality of life. The biomechanical properties of these two tissues are massively different from each other and they are not uniform within the same tissue due to the specific anatomic location and function. In this perspective, tissue engineering (TE) has emerged as a promising approach to address the complexities associated with bone and cartilage regeneration. Tissue engineering aims at developing temporary three-dimensional multicomponent constructs to promote the natural healing process. Biomaterials, such as hydrogels, are currently extensively studied for their ability to reproduce both the ideal 3D extracellular environment for tissue growth and to have adequate mechanical properties for load bearing. This review will focus on the use of two manufacturing techniques, namely electrospinning and 3D printing, that present promise in the fabrication of complex composite gels for cartilage and bone tissue engineering applications.

Keywords: 3D printing; bone; cartilage; composite hydrogels; electrospinning.

Figure 1

Schematic illustration of the basic setup for electrospinning. Reproduced from [62] with permission. Copyright (2015) Elsevier.

Figure 2

Effect of increasing applied voltage on the shape of the solution drop ejected by the needle: (a) normal dripping; (b) micro dripping; (c) intermittent Taylor cone; and (d) Taylor cone jet.

Figure 3

(a) Architectural framework of a native extracellular matrix (ECM); (b) electrospun 2D mat; (c) laminated hydrogel; and (d) fibres encapsulated into a hydrogel. Reproduced from [71] with permission. Copyright (2011) PMC.

Figure 4

Schematic overview of the method to fabricate 3D cell-laden laminated hydrogels. Reproduced from [69] with permission. Copyright (2016) Elsevier.

Figure 5

Schematic of the steps for the formation of nanoyarns using a water vortex. Reproduced from [82] with permission. Copyright (2007) Elsevier.

Figure 6

(A) SEM images of electrospun nanofiber mesh; (B) tubular implant without perforations; (C) tubular implant with perforations; (D) stabilized femur defect with implant; (E) bone defect, after placement of a perforated mesh tube; (F) alginate hydrogel was still present after 1 week, in vivo; and (G) release of rhBMP-2 from alginate hydrogel. Reproduced from [83] with permission. Copyright (2010) Elsevier.

Figure 7

Illustration of 3D bioprinting technologies based on the mechanism used to assist the deposition of the bioinks and its main components; (Left) Inkjet bioprinters eject small droplets of cells and hydrogel sequentially to build up the scaffold; (Middle) Laser bioprinters use a laser to generate the local ejection of small droplets from a donor ribbon coated with the bioink; (Right) Extrusion bioprinters uses pneumatic of mechanical forces to continuously extrude the bioink through a nozzle. Reproduced from [100] with permission. Copyright (2015) Wiley-VCH.

Figure 8

Schematic of the challenges for engineering bioinks suitable for 3D printing. Optimal shape fidelity can be typically achieved with stiff hydrogels (top right), however, this dense network limits cell viability. Contrarily, cell survive best in soft hydrogels, but shape fidelity cannot be achieved (bottom left). Therefore, a compromise between biological and fabrication properties must be done (middle). Novel strategies aimed at obtaining high shape fidelity with cytocompatible hydrogels. Reproduced from [105] with permission. Copyright (2009) Wiley-VCH.

Figure 9

3D printed constructs made of a composite hydrogel (alginate + nanofibrillated cellulose) seeded with human chondrocytes. (A) 3D printed small grids (7.2 × 7.2 mm²). Deformed grid during (B), and after (C) squeezing. (D) 3D printed human ear. (E, F) 3D printed sheep meniscus. Reproduced from [115] with permission Copyright (2015) American Chemical Society.

Figure 10

3D bio-printed constructs made of alginate/gelatin (AG) and alginate/gelatin/nano-HAp (AGH) mixed with human adipose-derived stem cells (hASCs) before and after implantation showing osteoinduction. Constructs were implanted into the back sub-cutaneous area of nude mice and harvested eight weeks after surgery. Larger bone formation was observed in the constructs containing HAp. Reproduced from [140] with permission, Copyright (2016) Royal Society of Chemistry.