Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.

3D bioprinting of tissues and organs

Despite intensive research, hydrogels currently available for tissue repair in the musculoskeletal system are unable to meet the mechanical, as well as the biological, requirements for successful outcomes. Here we reinforce soft hydrogels with highly organized, high-porosity microfibre networks that are 3D-printed with a technique termed as melt electrospinning writing. We show that the stiffness of the gel/scaffold composites increases synergistically (up to 54-fold), compared with hydrogels or microfibre scaffolds alone. Modelling affirms that reinforcement with defined microscale structures is applicable to numerous hydrogels. The stiffness and elasticity of the composites approach that of articular cartilage tissue. Human chondrocytes embedded in the composites are viable, retain their round morphology and are responsive to an in vitro physiological loading regime in terms of gene expression and matrix production. The current approach of reinforcing hydrogels with 3D-printed microfibres offers a fundament for producing tissue constructs with biological and mechanical compatibility.

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Reinforcement of hydrogels using three-dimensionally printed microfibres

Progress in 3D bioprinting technology for tissue/organ regenerative engineering

Biodegradable polymers have met with an increasing demand in medical usage over the last decades. One of such polymers is poly(e-caprolactone) (PCL), which is a polyester that has been widely used in tissue engineering field for its availability, relatively inexpensive price and suitability for modification. Its chemical and biological properties, physicochemical state, degradability and mechanical strength can be adjusted, and therefore, it can be used under harsh mechanical, physical and chemical conditions without significant loss of its properties. Degradation time of PCL is quite long, thus it is used mainly in the replacement of hard tissues in the body where healing also takes an extended period of time. It is also used at load-bearing tissues of the body by enhancing its stiffness. However, due to its tailorability, use of PCL is not restricted to one type of tissue and it can be extended to engineering of soft tissues by decreasing its molecular weight and degradation time. This review ou...

PCL and PCL-based materials in biomedical applications

During the resorbable-polymer-boom of the 1970s and 1980s, polycaprolactone (PCL) was used in the biomaterials field and a number of drug-delivery devices. Its popularity was soon superseded by faster resorbable polymers which had fewer perceived disadvantages associated with long term degradation (up to 3-4 years) and intracellular resorption pathways; consequently, PCL was almost forgotten for most of two decades. Recently, a resurgence of interest has propelled PCL back into the biomaterials-arena. The superior rheological and viscoelastic properties over many of its aliphatic polyester counterparts renders PCL easy to manufacture and manipulate into a large range of implants and devices. Coupled with relatively inexpensive production routes and FDA approval, this provides a promising platform for the production of longer-term degradable implants which may be manipulated physically, chemically and biologically to possess tailorable degradation kinetics to suit a specific anatomical site. This review will discuss the application of PCL as a biomaterial over the last two decades focusing on the advantages which have propagated its return into the spotlight with a particular focus on medical devices, drug delivery and tissue engineering.

The return of a forgotten polymer : Polycaprolactone in the 21st century

State of the art composites comprising electrospun fibres coupled with hydrogels: a review.

Physicochemical characterisation of degrading polycaprolactone scaffolds

Two-dimensional (2D) electrospun fibre mats have been investigated as fibrous sheets intended as biomaterials scaffolds for tissue repair. It is recognised that tissues are three-dimensional (3D) structures and that optimisation of the fabrication process should include both 2D and 3D scaffolds. Understanding the relative merits of the architecture of 2D and 3D scaffolds for tendon repair is required. This study investigated three different electrospun scaffolds based on poly(e-caprolactone) fibres intended for repair of injured tendons, referred to as; 2D random sheet, 2D aligned sheet and 3D bundles. 2D aligned fibres and 3D bundles mimicked the parallel arrangement of collagen fibres in natural tendon and 3D bundles further replicated the tertiary layer of a tendon’s hierarchical configuration. 3D bundles demonstrated greatest tensile properties, being significantly stronger and stiffer than 2D aligned and 2D random fibres. All scaffolds supported adhesion and proliferation of tendon fibroblasts. Furthermore, 2D aligned sheets and 3D bundles allowed guidance of the cells into a parallel, longitudinal arrangement, which is similar to tendon cells in the native tissue. With their superior physical properties and ability to better replicate tendon tissue, the 3D electrospun scaffolds warrant greater investigation as synthetic grafts in tendon repair.

Investigation of 2D and 3D electrospun scaffolds intended for tendon repair

Electrospinning commonly requires a solvent carrier to transform polymer materials from one solid form to another. The types of solvents are often classed as toxic and hazardous and have potential long-term impacts on the environment and the health of the user. Acetone is a sustainable and non-toxic solvent, but has received limited use within the electrospinning sector—particularly for biocompatible polymers, such as poly(e-caprolactone) (PCL). This paper documents the ability to electrospin PCL dissolved in acetone and the effects of spinning parameters on the morphology and diameter of the collected fibres. Depending on the end use of the collected fibres it is important to understand how the parameters interplay and affect fibre morphology and diameter, especially if fibres of a specific form and size are required, for example, to mimic the extracellular matrix of tissues. This paper investigates the effects of flow-rate (0.05 and 0.1 ml/min), voltage (15 and 25 kV), distance (5 and 10 cm) and voltage-distance combined, on different concentrations of poly(e-caprolactone)/acetone solutions (5, 7.5 and 10 %w/v) in terms of fibre morphology and fibre diameter. Overall, solutions of PCL dissolved in acetone could be electrospun and, in general, the trends observed with altering spinning parameters followed those documented for other polymer/solvent systems. This calls for the increased use of less hazardous and more sustainable solvents, such as acetone, for electrospinning applications.

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Acetone, a Sustainable Solvent for Electrospinning Poly(e-Caprolactone) Fibres: Effect of Varying Parameters and Solution Concentrations on Fibre Diameter

Part 1 Introduction Polymer chemistry Process control Regulatory issues. Part 2 Electrospinning for organ tissue regeneration: Blood vessel tissue regeneration Cartilage tissue regeneration Nerve tissue regeneration Muscle tissue regeneration Skin tissue regeneration Bladder tissue regeneration Renal tissue regeneration Cardiac tissue regeneration Pancreactic tissue regeneration Liver tissue regeneration Tendon tissue regeneration Bone tissue regeneration. Part 3 Electrospinning for other tissue regeneration: Interface region (tendon/bone) applications Stem cell regeneration Wound healing applications Bicomponent Electrospinning Dental restoration.

Lucy A. Bosworth

Papers

State of the art composites comprising electrospun fibres coupled with hydrogels: a review.

Physicochemical characterisation of degrading polycaprolactone scaffolds

Investigation of 2D and 3D electrospun scaffolds intended for tendon repair

Acetone, a Sustainable Solvent for Electrospinning Poly(e-Caprolactone) Fibres: Effect of Varying Parameters and Solution Concentrations on Fibre Diameter

Electrospinning for tissue regeneration