Biomaterial Fabrication Techniques

Biomaterials are essential elements in various fields, especially medicine. They can help restore biological functions and speed up the healing process after injury or disease. Natural or synthetic biomaterials are used in clinical applications to provide support, replace damaged tissue, or restore biological function. The study of such types of biomaterials is an active area of research, particularly in the field of tissue engineering (TE). In general, the term TE describes the regeneration, growth, and repair of damaged tissue due to disease or injury. TE is a modern science that combines biology, biochemistry, clinical medicine and biomaterials, which led to the research and development of various applications. For example, in the field of regenerative medicine, biomaterials can serve as a support (scaffold) to promote cell growth and differentiation, which ultimately facilitates the healing process of tissues. This chapter describes the various properties of biomaterials, a detailed discussion of scaffolds in terms of design, properties and production techniques, and future directions for TE. 

The goal of tissue engineering is to restore damaged tissue by combining cells with biomimetic material to initiate the growth of new tissue. Biomimetic material plays a crucial role in tissue engineering as it serves as a template and is responsible for providing a suitable environment for tissue development, which includes adhesion of cells, their proliferation and deposition of extracellular matrix. Biocomposites are composite materials, consisting of one or more multiphase materials of biological origin. In this chapter, the biocomposites used for tissue engineering are described in detail. The chapter also highlights the scaffolds and their mechanical properties. This chapter also includes various materials used for scaffold fabrication.

The freeze-drying process involves solvent sublimation under vacuum from pre-frozen solution resulting in porous materials. Pore volume, pore size, and density depend on several variables, including freezing temperature, solute and solvent type, solution concentration, and freezing direction. Researchers have investigated aqueous and organic solutions, supercritical CO2 solutions, and colloidal solutions to produce various porous structures. A more recent process involves freeze-drying of emulsions, which leads to controlled pore volume and pore morphology, and porous organic nanomaterials. Directional and spray freezing are used to produce aligned porous materials and porous particles. In this chapter, we describe the basic principles of the freeze-drying process, the factors affecting the porosity of freeze-dried biomaterials, and their biomedical applications. The freeze-dried porous biomaterials are discussed in detail based on their morphology: porous structures, micro- nanowires, and micronanoparticles. We have summarised the current status and given some directions for future research in this field.

Nanofibers are a necessary source for fibrous materials and other useful applications such as tissue engineering, filtration, safety fabrics, batteries for the production of nanofibers so far. However, due to its low production rate, the wide commercial use of electrospinning is minimal. Almost all nanofiber fabrication techniques (e.g., melt blowing, two-component processes, phase splitting, template synthesis, and self-assembly, etc.) are used to produce nanofibers from a limited number of polymeric materials. Centrifugal spinning (CS) and solution blow spinning (SBS) are advanced replacement processes to fabricate nanofibers with full performance from various low-cost raw materials. This chapter focuses on a comprehensive overview of CS and SBS as well as various other aspects of the fabrication of nanofibers.

The electrospinning (ES) technique in the fabrication of biomaterials-based electrospun nanofibers (ESNFs) has risen to prominence because of its accessibility, cost-effectiveness, high production rate and diverse biomedical applications. The ESNFs have unique characteristics, such as stability and mechanical performance, high permeability, porosity, high surface area to volume ratio, and ease of functionalization. The characteristics of ESNFs can be controlled by varying either process variables or biomaterial solution properties. The active pharmaceutical agents can be introduced into ESNFs by blending, surface modification, or emulsion formation. In this chapter, in the first part, we briefly discuss the fundamental aspects of the fabrication, commonly used materials, process parameters, and characterization of ESNFs. In the second part, we discuss in detail the biomedical applications of ESNFs in drug delivery, tissue engineering, and wound healings, cancer therapy, dentistry, medical filtration, biosensing and imaging of disease. 

Over the past decade, three-dimensional printing (3DP) has gained popularity among the public and the scientific community in a variety of disciplines, including engineering, medicine, manufacturing arts, and, more recently, education. The advantage of this technology is that it is capable of designing and printing almost any object shape using various materials such as ceramics, polymers, metals and bioinks. This has further favored the use of this technology for biomedical applications in both clinical and research settings. In biomedicine, there has been a remarkable development of a variety of biomaterials, which in turn has accelerated the significant role of this technology as synthetic scaffolds in various forms such as scaffolds, constructs or matrices. In this chapter, we would like to review the trailblazing literature on the application of 3DP technology in biomedical engineering. This chapter focuses on various 3DP techniques and biomaterials for tissue engineering applications (TE). 3DP technology has a variety of applications in biomedicine and TE (B- TE). Customized structures for B- TE applications using 3DP have several advantages, e.g., they are easy to fabricate and are inexpensive. On the other hand, conventional technologies, which are costly, time-consuming, and labor intensive, are generally not compatible with 3DP. Therefore, the capabilities of 3DP, which is a novel fabrication technology, need to be explored for many other potential applications. Here, we provide a comprehensive overview of the different types of 3DP technologies and how they can potentially be used.

The use of polymers in the development of biomaterials for various biomedical applications has become increasingly important in recent decades. To match the innate properties of biological tissues, the polymer-based tissue scaffolds must have the desired structural and functional properties. However, the polymer-based hydrogels prepared by conventional methods are often delicate and fragile and require pre-stabilisation. This necessitates the exploration of bio-friendly cross-linkers that promote kinetic or reversible crosslinking in the polymer network of hydrogels and must be nontoxic to cells and tissues. The light initiators with well-organized multiphoton cross sections that are reactive at specific wavelengths could be ideal candidates. This chapter reviews the fabrication of solid or viscoelastic biological scaffolds by multiphoton lithography (MPL) of liquids. It describes the similarities and differences between conventional and MPL photo polymerization of biological scaffolds in terms of synthesis chemistry, properties, and their relevance to biological applications. These photosensitive scaffolds could be useful biomaterials for their biomedical applications.

The most important characteristic of a scaffold used in tissue engineering is the possession of appropriate physical and mechanical properties to support or restore the biological function of damaged or degenerated tissue. Pore size, porosity, pore interconnectivity, and mechanical strength are all physical and mechanical properties that must be considered. Various fabrication techniques have been investigated to create a scaffold suitable for tissue engineering. One example is the particulate leaching (salt leaching) technique. The type of polymers and salts used, the particle size of the salt, and the fabrication technique all affect the desired physical and mechanical properties of salt leaching scaffolds. Over the past decade, there have been numerous studies on the fabrication of scaffolds for tissue engineering. This chapter reviews the different types of materials used, the basic salt leaching process, and its new modifications. It also discusses the advantages and disadvantages of the salt leaching technique and its future prospects. 

Tissue engineering techniques aim to create a natural tissue architecture using biomaterials that have all the histological and physiological properties of human cells to replace or regenerate damaged tissue or organs. Nanotechnology is on the rise and expanding to all fields of science, including engineering, medicine, diagnostics and therapeutics. Nanostructures (biomaterials) specifically designed to mimic the physiological signals of the cellular/extracellular environment may prove to be indispensable tools in regenerative medicine and tissue engineering. In this chapter, we have discussed biomaterial design from two different perspectives. Supramolecular self-assembly is the bottom-up approach to biomaterials design that takes advantage of all the forces and interactions present in biomolecules and are responsible for their functional organization. This approach has the potential for one of the greatest breakthroughs in tissue engineering technology because it mimics the natural, complex process of coiling and folding biomolecules. In contrast, a fiber mesh scaffold is a topdown approach in which cells are seeded. The scaffolds form the cellular scaffold while the cells produce and release the desired chemical messengers to support the regeneration process. Therefore, both techniques, if efficiently explored, may lead to the development of ideal biomaterials produced by self-assembly or by the fabrication of optimal scaffolds with long shelf life and minimal adverse reactions.

Biomaterials are receiving tremendous attention, especially in the biomedical field, due to their impressive structural, physiological, and biological properties, such as nontoxicity, biocompatibility, and biodegradability. Numerous biomaterials have been used to fabricate scaffolds for applications in tissue engineering and regenerative medicine, where they are used as wound dressings, grafts, organs, and substitutes. To date, a number of techniques have been developed for the fabrication of scaffolds from biomaterials. This chapter focuses on the fabrication of scaffolds by solvent casting and melt-casting techniques. It examines the solvent casting and meltcasting techniques in terms of their application in the fabrication of biological scaffolds with tailored micro- and nanostructures for their use in tissue engineering. The merits and limitations of these techniques in fabricating biological scaffolds for desired biomedical applications are also discussed. Finally, various challenges faced by solvent and melt casting techniques are described, and solutions are proposed for future research to develop biomaterials for advanced biomedical applications.