Virtual Prototyping & Bio Manufacturing in Medical Applications

Artificial vascular vessels, including arteries, veins and capillaries, are being printed using additive manufacturing technologies. Additive manufacturing allows the manufacture of artificial blood vessels and their networks of any sophisticated geometry. This chapter demonstrates the essential and efficient methods to design and fabricate optimal vascular network for tissue engineering structures following the physiological conditions. Comprehensive physiological requirements in both micro- and macro-scales were considered in developing the optimisation design for artificial vascular networks. The optimised vascular vessel offers three advantages: (1) it provides the maximum nutrient supply; (2) it minimises the recirculation areas and (3) it allows the wall shear stress on the vessel in a healthy range. Two main design technologies are used in the chapter to achieve the design. They are computer graphics and computational fluid dynamics. The optimised design was then manufactured by the stereolithography process using materials that are biocompatible, elastic and surface bio-coatable. The stereolithography manufactured vascular vessels were embedded in the hydrogel seeded with cells afterward. The results of in vitro studies show that the optimised vascular network has the lowest cell death rate compared with a pure hydrogel scaffold and a hydrogel scaffold embedded within a single tube in day seven. The combination of the optimised micro- and macro-design, the material selection and the manufacturing methods completes a general guide for future artificial vascular vessel network developments.

Virtual Reality (VR) technologies provide a realistic, safe, and controllable environment for novice surgeons to practice surgical operations, allowing them to make mistakes without serious consequences, which have been changing the world of surgical training and practice. This book chapter focuses on methodologies and applications of utilizing VR techniques for bone surgical simulations. First, the current state of the surgical simulation, including a brief history and some recent typical studies, is reviewed. Then, the key technologies for developing bone surgery simulation systems are identified. Furthermore, the basic methods and techniques used to develop such surgical simulation systems are clarified in detail, including medical image processing and segmentation, geometric modeling and data manipulation, graphic rendering, haptic rendering, and auditory rendering. Finally, a chapter summary and some future research needs are presented.

The development of techniques and equipment for medical imaging has provided physicians with efficient, fast, and reliable resources for diagnostic tasks. Large volumes of three-dimensional (3D) data can be stored, analyzed, and visualized through non-invasive procedures, whose interpretation has led to advances in disease assessment, surgical planning, treatment monitoring, among other benefits in healthcare. This chapter describes relevant concepts related to medical imaging techniques for the construction of three-dimensional models for visualization and biofabrication.

A novel CAD system of structures based on convex polyhedral units has been created for use with rapid prototyping (RP) technology in tissue engineering applications. The prototype system is named the Computer Aided System for Tissue Scaffolds or CASTS.

CASTS consists of a basic library of units that can assemble uniform matrices of various shapes. Each open-cellular unit is a unique configuration of linked struts. Together with an algorithm which allows the designer to specify the unit cell and the required dimensions, the system is able to automatically generate a structure that is suitable for the intended tissue engineering application. Altering the parameters can easily change the desired shape and spatial arrangement of the structures.

The main advantage of CASTS is the elimination of reliance on user skills, much unlike conventional techniques of scaffold fabrication. From a small range of basic units, many different scaffolds of controllable architecture and desirable properties can be designed. The system interface of CASTS in Pro/ENGINEER is user friendly and allows complete transfer of knowledge between users without the need for complex user manuals.

A femur implant was successfully fabricated using selective laser sintering (SLS) and a standard commercial material Duraform™ polyamide. However, it was seen that there was some raw powder trapped inside the concept model and further investigations were carried out to minimise the incidence of trapped powder in the scaffolds. A disc shape scaffold was designed for this purpose. In this disc-shaped design, four different strut lengths were used, resulting in four different pore sizes and porosity. Scaffolds of the one-unit layer cells built using Duraform™ polyamide were then examined under a light microscope to check the consistency and reproducibility of the microstructures.

Three types of biomaterials were tested on CASTS: PEEK, PEEK-HA biocomposite, and PCL. The scaffolds built showed very good definition of the pre-designed microarchitecture and were readily reproducible. While delamination occurred at larger unit cell sizes, this had no effect on the overall shape or the structural integrity of the scaffolds.

The potential of this system lies in its ability to design and fabricate scaffolds with varying properties through the use of different unit cells and biomaterials to suit different tissue engineering applications.

Tissue engineering is a rapidly expanding multidisciplinary and interdisciplinary field exploiting biomaterials, living cells, and biomolecular signals to produce constructs to restore, maintain, or enhance the function of tissues or organs. Additive manufacturing, with a high degree of freedom either for the design of scaffolds (pore size, pore geometry, orientation, interconnectivity, etc.) or for its fabrication, obtains significant attentions in the field of tissue engineering. This book chapter introduces the concept of tissue engineering and main tissue engineering strategies. It discusses the role and main requirements of scaffolds as well as reviewing the main conventional and additive manufacturing techniques used to produce scaffolds for tissue engineering.

Following nervous system injuries, such as peripheral or spinal cord injuries, severed nerves must regenerate to reinnervate tissues and restore lost-functionality. In many peripheral nerve injuries surgical intervention is required to bridge the gaps created and facilitate regrowth. The gold standard for peripheral nerve repair remains end-to-end suturing and nerve grafting, yet, these still present unmet challenges and limitation including misalignment of regenerating axons. Following spinal cord injuries currently there are no therapies capable of complete nerve restoration. Tissue engineering strategies include the design of structured tissue-like platforms to support growth and facilitate reconstructions of damaged tissues for both the peripheral and the central nervous systems. In the last two decades efforts to increase accuracy of regeneration through engineering growth-and-alignment promoting platforms have emerged as potential alternatives for grafting techniques, demonstrating advantageous effects in vitro and in vivo. This chapter reviews tissue engineering techniques and advanced fabrication strategies for oriented scaffolds and nerve repair conduits developed to aid nerve repair.

The electrospinning technology is one of the most versatile and relevant non-mechanical, electrostatic processes to produce nano-scale meshes. The technology has a wide range of application areas from tissue engineering such as wound dressings, nerve tissues to textile and filter applications. Therefore, researches on the electrospinning technology have been rapidly increased in the last two decades in both academia and industry. The electrospinning process can be classified according to the materials used, number of nozzles, applied voltage and working conditions. Usually, the system involves ejecting a polymer solution (solution electrospinning) or melt (melt electrospinning) from a syringe needle tip, by applying a high electric field. Even though the system has three main devices (high power supply, a needle and collector) to produce the nano-scale meshes, it has various parameters (solution, process and ambient parameters) that have effect on the fibre quality and morphology. This chapter will discuss the types of electrospinning systems and their protocols for the fabrication of the fibres and solution, process and ambient parameters relevant to electrospinning and their effect on the morphology of the fibres.

Scaffold-based approach is a developed strategy in biomanufacturing, which is based on the use of temporary scaffold that performs as a house of implanted cells for their attachment, proliferation, and differentiation. This strategy strongly depends on both materials and manufacturing processes. However, single material is very difficult to meet all the requirements such as biocompatibility, biodegradability, mechanical strength, and promotion of cell adhesion. No single bioprinting technique currently can meet the requirements for all scales tissue regeneration. Thus, multi-material and mixing-material scaffolds have been greatly investigated. Challenges in terms of resolution, uniform cell distribution, and tissue formation are still severe in the field of bioprinting technique development. Hybrid bioprinting techniques have been developed to print scaffolds with improved properties in both mechanical and biological aspects for broad biomedical engineering applications. In this review, we introduce the basic multi-head bioprinters, semi-hybrid and fully hybrid biomanufacturing systems, highlighting the introduced modifications, improved properties, and the effect on the complex tissue regeneration applications.

Low back pain is believed to affect 80% of the world’s population at some point in their lifetime. In the UK alone, it is one of the main causes of work absenteeism and decreased quality of life. Degenerative disc disease and intervertebral disc (IVD) herniation (i.e., “slipped disc”) are the main causes of low back pain and sciatica. Discectomy and microdiscectomy, two of the most commonly used surgical procedures, aim to remove the tissue exerting pressure on the nerves and thus relieve the pain. However, this is only a temporary solution as damage to the IVD is not repaired and may require additional surgical interventions. While this procedure is less aggressive in comparison to spinal disc arthroplasty and fusion, microdiscectomy still requires a down-time of 1–4 weeks post-surgery. Emerging treatments for IVD repair aim to address these concerns, novel NP and AF repair strategies are being developed based on novel additive manufacturing techniques.

The World Health Organization predicted that by 2020 trauma cases are going to be the main reason of death. Internal fixations “bone fixation plates” currently used to treat bone fractures present significant drawbacks that decrease the healthcare quality and increase its costs. Biocompatible metallic materials such as titanium and its alloys (e.g., Ti-6Al-4V) and 316L stainless steel are used for internal fixations. Current internal fixation drawbacks are: it requires pre-shaping to anatomically fit the patient (personalisation); a second surgery required to remove the implant with the possibility of bone refracture; if the implant remains in the body, metal toxicity/carcinogenic effects may occur; stress shielding possibility may increase due to the mechanical properties mismatch between the metallic implant and the native bone. This review presents an insight to address the mentioned limitations through additive manufacturing, and in particularly metallic powder bed fusion techniques. Different and successful cases aiming to personalise internal fixation implants and to minimise stress shielding are presented. On the other hand, for the metallic implant second surgery requirement and its possibly long-term toxicity, extensive ongoing research on different biodegradable materials are considered. Research future and challenges are also discussed.

Nerve defects that exceed a critical size represent a major clinical problem due to the limited ability for nerve regeneration. Nerve injury could cause serious disabilities and affect a patient’s health for lifetime. Since the clinical results of traditional treatment are usually unsatisfactory, the most relevant strategies are based on the use of the scaffold, which aims to carry out regeneration of tissue by using cells, biomaterial or scaffold and growth factors. This chapter introduces the structure and the regeneration process of the nerve tissue and explains the current treatment methods that can be used to treat nerve injury. Besides, this chapter also introduces the design requirements for nerve scaffold and the additive manufacturing technique for scaffold fabrication.