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USE OF BIOPRINTING IN REGENERATIVE MEDICINE

Additive manufacturing, which is more commonly (but less accurately) known as 3D printing, involves the building of three-dimensional (3D) objects by adding successive layers of materials.  Many different types of materials, including polymers, metals, concrete, and ceramics, can be used in 3D printing processes. The techniques and equipment available to perform 3D printing are improving rapidly as 3D printing progresses towards fulfilling its promise to revolutionize many areas of industry.

Regenerative medicine is an application area in which 3D printing is likely to make many breakthrough contributions, providing improvements to human health and quality of life that may not have been achievable with any other type of technology.  Intensive research and development is in progress worldwide to develop improved techniques, equipment, and processes to manufacture human tissues and organs by 3D printing.

Bioprinting is the additive manufacturing of tissues and organs.  It shows great potential in tissue engineering, for the reproducible and very accurate fabrication of scaffolds, cells, tissues, and organs.  More specifically, bioprinting provides precise and repeatable control over construct geometry, composition, and configuration, such attributes not generally being associated with traditional tissue construct fabrication techniques. 

The three main categories of bioprinting methods are inkjet-based bioprinting, pressure-assisted bioprinting, and laser-assisted bioprinting.  Each method has its own advantages and limitations, based on its own underlying printing principles.  Inkjet-based bioprinting is an adaptation of the conventional inkjet printing process, with desktop inkjet printers, to the deposition of biomaterials onto substrates.  Extrusion bioprinting, which is the most commonly implemented form of pressure-assisted bioprinting, applies extrusion to deposit biomaterials.  Laser-assisted bioprinting uses a laser as the energy source to deposit biomaterials.  Great progress has been made already in printing various types of tissue, including vasculature, heart, bone, cartilage, skin, and liver.

Figure 2 from the open access review article by Wang, X.; Ao, Q.; Tian, X.; Fan, J.; Wei, Y.; Hou, W.; Tong, H.; Bai, S.; 3D Bioprinting Technologies for Hard Tissue and Organ EngineeringMaterials, 2016, 9, 802, which is reproduced below, summarizes the working principles of laser-assisted bioprinting, inkjet-based bioprinting, and extrusion bioprinting.

This review article cites [22] Ozbolat, I.T.; Yu, Y. Bioprinting toward organ fabrication: Challenges and future trends, IEEE Trans. Biomed. Eng., 2013, 60, 691–699, as the original source of Figure 2.

A bioink is a material utilized in bioprinting.  Bioprinting utilizes biomaterials, cells, or cell factors as bioinks to fabricate prospective tissue structures.  Biomaterial parameters, such as biocompatibility, cell viability, and the cellular microenvironment, strongly influence the bioprinted product.  Bioinks play key roles in structural support, adhesion, and differentiation of incorporated cells.  Bioinks may be classified on the basis on their ultimate role in a 3D bioprinted construct; such as imparting biological functionality, serving as a sacrificial material, or supporting and providing rigidity to complex constructs. 

There are many potential bioinks due to the diversity of tissue types found in the body and the need to reproduce many structural and functional characteristics of a target tissue.  Physical, mechanical, and biological characteristics must all be taken into account in the design and composition of bioinks.  For example, biomaterials used for skin bioprinting must be printable, biodegradable but stable for at least 3 weeks to allow the completion of the skin regeneration process, acceptable in terms of their mechanical properties, and biocompatible with immobilized cells.  Most importantly, a bioink must possess two different phases and must be capable of changing from one form to another.  It must have a liquid phase with subsequent solidification to keep a rigid form once printed.  Since most bioinks do not possess optimal properties yet, their improvement is the focus of much research.

Many biopolymers are either used as or candidates for use as bioinks.  For example, candidates for skin bioprinting include natural biopolymers; such as the polysaccharides chitosan, alginate, and hyaluronic acid; the proteins collagen, gelatin (hydrolyzed collagen), elastin, fibrin, and silk; and various hydrogels of polysaccharides with proteins (such as chitosan or hyaluronic acid with gelatin).  Candidates for skin bioprinting also include synthetic biopolymers; such as poly(lactic acid), poly(lactic-co-glycolic acid), poly(ε-caprolactone), poly(ethylene glycol), medical grades of polyurethanes, and self-assembling peptides.  The construction of composite tissue scaffolds combining inherently biocompatible natural biopolymers with mechanically stronger synthetic biopolymers is also promising.

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