Current standards and ethical landscape of engineered tissues—3D bioprinting perspective

Abstract

Tissue engineering is an evolving multi-disciplinary field with cutting-edge technologies and innovative scientific perceptions that promise functional regeneration of damaged tissues/organs. Tissue engineered medical products (TEMPs) are biomaterial-cell products or a cell-drug combination which is injected, implanted or topically applied in the course of a therapeutic or diagnostic procedure. Current tissue engineering strategies aim at 3D printing/bioprinting that uses cells and polymers to construct living tissues/organs in a layer-by-layer fashion with high 3D precision. However, unlike conventional drugs or therapeutics, TEMPs and 3D bioprinted tissues are novel therapeutics and need different regulatory protocols for clinical trials and commercialization processes. Therefore, it is essential to understand the complexity of raw materials, cellular components, and manufacturing procedures to establish standards that can help to translate these products from bench to bedside. These complexities are reflected in the regulations and standards that are globally in practice to prevent any compromise or undue risks to patients. This review comprehensively describes the current legislations, standards for TEMPs with a special emphasis on 3D bioprinted tissues. Based on these overviews, challenges in the clinical translation of TEMPs & 3D bioprinted tissues/organs along with their ethical concerns and future perspectives are discussed.

Meniscus regeneration by 3D printing technologies: Current advances and future perspectives

“…Moreover, denaturalization of the biomaterials and inconsistent ink droplets can also occur. 108 , 112 , 114 , 115 …”

“…Extrusion-based methods work dispensing bioink in a continuous filament to produce a 3D structure organized in a layer-by-layer manner 112 ; printing speed is set at 0.1–150 mm/s 108 According to the dispensing method, pneumatic-extrusion bioprinters or mechanical-extrusion bioprinters can be distinguished; moreover, the mechanical-extrusion bioprinters can also be divided in piston-systems or screw-driven systems. 116 …”

“… 112 Other critical issues include frequent blockage of the nozzles and shear-induced cell death (cell viability ranging from 60% to 90%). 108 , 117 …”

“…Extrusion-based approaches has been reported in example with alginate, gelatin, gellan gum, guar gum, methylcellulose, collagen type I, matrigel, fibrinogen, collagen methacrylate, GelMA, elastin, polycaprolactone (PCL), polyethylene glycol (PEG), polyvinyl alcohol (PVA), and polyvinyl acetate. 108 …”

Biobridge: An Outlook on Translational Bioinks for 3D Bioprinting

“…[ 23 ] The logistical challenges of validating the procurement, processing, storage of human cells and the costs associated with meeting stringent regulatory and ISO (International Organization for Standardization) standards have significantly limited the number of tissue‐engineered medicinal products available in market. [ 24 , 25 ] 3DBP confronts similar challenges and has many overlapping elements with TE as illustrated in Figure 1 . Therefore, the regulations for gene & cell therapies, and the current standard for preclinical testing of implantable medical devices (ISO 10993‐1:2018), [ 26 ] and additionally, the current legislation and regulations on tissue‐engineered medical products in different countries which has been summed up in a recent review [ 25 ] should provide valuable references for the development of implantable clinical products based on 3DBP.…”