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International Journal of Bioprinting dECM bioink for in vitro disease modeling

should be subjected to immunogen removal to enhance associated with 3D bioprinting and dECM bioinks that are
biocompatibility. 98 currently emerging are discussed as follows.
The use of toxic chemicals in the aforementioned The source of biomaterials and dECM bioink applied
decellularization and crosslinking processes gives in 3D bioprinting is an important ethical consideration.
rise to problems regarding cell survival and tissue In compliance with ethical regulations, clarifications on
necrosis, while incomplete cell removal following the how human or animal tissues and cells are obtained and
decellularization process causes heterogeneous immune used are needed. This may cover a wide range of aspects,
responses. To address these problems, it is necessary such as tissue and cell donation procedure, consent giving,
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to fundamentally analyze the effect of decellularization and protection of personal data. Additionally, research
and crosslinking processes on ECM composition. Most and complete verification of the safety and hazards of the
current decellularization processes use a variety of toxic biomaterials used are required. The use of unidentified
chemicals, which are detrimental to the preservation materials or techniques that pose a risk to patients should
of the unique ECM composition; therefore, improved be avoided. In the case of 3D bioprinting, digital 3D models
decellularization technology is required. To avert this should be treated as personalized human data; thus, the
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problem, Topuz et al. used supercritical carbon dioxide protection of human identifiable information must be
(scCO ) in the decellularization process to minimize considered under the context of privacy laws. Additionally,
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changes to the ECM composition. Moreover, an when cells and tissues are obtained from patients or donors,
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advanced rapid detection method to determine whether informed consent must be obtained.
residual toxic and cellular components remain in the Furthermore, ethics committee approval for conducting
dECM should be developed, and a standardized quality research or clinical trials involving dECM bioinks is
control protocol should be conducted in order to resolve required, and there is a need to harmonize these protocols
this issue.
globally. Currently, there are no unified regulations in this
Proper resolution of the aforementioned issues could regard; thus, a set of comprehensive unified regulations
facilitate the utilization of dECM for the production of should be drafted and officiated as soon as possible to
more precise normal and disease models and the process protect the safety of research participants and ensure the
of tissue regeneration for various organs. Medical products compliance to the bioethical principles. For reference,
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for skin regeneration have already been developed using the European Medicines Agency regulates several tissue-
skin-derived dECM, such as AlloDerm® (BioHorizons) engineered products as advanced therapy medicinal
and Oasis® (Smith & Nephew). 237,238 A hydrogel bioink products (ATMPs) under the Gene Therapy Act.
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called deCelluid™ (T&R Biofab), which is applicable to 3D Because the central idea of combining 3D bioprinting
bioprinting and created from bone-derived dECM, has technology with dECM bioink serves the similar purposes
also been developed. However, only dECMs applicable as the production of ATMPs, unified regulations on this
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to the fabrication of a limited selection of organ models matter can be formulated in reference to the relevant acts.
have been commercialized, and clinical cases describing Additionally, to ensure that products stemming from the
the application of these dECMs remain scanty. Therefore, combination of 3D bioprinting and dECM bioink are safe,
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it is necessary to standardize and commercialize dECM efficacious, and of good quality, protocols concerning the
bioinks for a wider range of organs and to conduct more production, marketing, and utilization of dECM bioink
clinical trials to validate their reliability. must be set in compliance with local laws and regulations.
Finally, ethical and legal issues need to be addressed Furthermore, it is important to note that commercial use
for more efficient use of 3D bioprinting and dECM bioink. of relevant technologies and dECM bioink may give rise
3D bioprinting and dECM bioink have the potential to intellectual property infringement issues. Thus, caution
to overcome various ethical issues that fall within the must be exercised with regard to the development and sale
realms of indiscriminate animal testing, clinical trials, of bioinks, and the patents and copyrights of established
and organ transplantation. At present, however, there has inventions must always be respected.
been no in-depth discussion regarding the ethical and In conclusion, 3D bioprinting using dECM bioink
legal issues related to 3D bioprinting and dECM bioink. is expected to achieve wide-scale application for the
Aside from the problems with printing technology, development of various intractable disease models and
issues concerning biology, bioethics, and philosophy are personalized models through the simulation of organ-
catching our attention since a variety of human and animal specific microenvironments. Additionally, this technique
derivatives, including cells, are employed in the process of is anticipated to be applicable to the fabrication of artificial
3D bioprinting. Some of these ethical and legal issues organs for organ transplantation.
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Volume 10 Issue 2 (2024) 152 doi: 10.36922/ijb.1970