Photo courtesy- Cruelty Free International  ( EU banned cosmetics animal testing & Leaping Bunny)

Author- S. Dravida, Founder and CEO, Transcell Biologics, Hyderabad, Telangana, India

Transcell Oncologics offers primary human biological discards sourced characterized pluripotent stem cell based platforms as tools to integrate in 3D bioprint technology.

Humanizing 3D prints to use as Alternatives to Animals in Pharmaceutical testings

Bioprinting is a bio-manufacturing process where biomaterials such as cells and growth factors are combined to create tissue-like structures that imitate natural tissues outside of human body while bioink is used to create layers of these structures. Since the past decade, 3D bioprinting is widely applicable to the fields of medicine and bioengineering; reconstruction and regeneration. The bioprinted tissues can be clinically utilized like in tissue/organ transplantation or for invitro modelling with a role in pre-clinical drug discovery and development.

In terms of cell sources for bioprinting, the ones that have the capabilities to retain, recapitulate the tissue specific biological function along with proliferating capacities are known to be the best options. It is known that primary tissue or biopsy derived cells have limitations with above cited properties provoking our mind towards Stem Cells.

Stem cells, on the brighter side, have the properties of self-renewal and differentiation potency, representing an unlimited cell supply if the source is biological discards.

3D bioprinting of Cardiovascular tissue

Transplantation is the only viable treatment option for end-stage heart failure. 3D stem cell bioprinting approaches have huge implications in regenerative medicine, for disease modeling and treatment of heart disease and heart failure, as well as for toxicological studies and personalized drug testing. 

3D bioprinting of Musculoskeletal tissue

Biological micro electromechanical system devices conjugated with bioprinted skeletal muscle tissue offer promising methods of developing novel bioengineering microdevices such as motors, actuators, heart pumps, and biosensors. Bioprinted myotubes can be used in muscle exercise studies, can be used to improve material design of treatments for musculoskeletal diseases and trauma, for regenerative medicine applications.

3D bioprinting of Neural tissue

3D stem cell bioprinting of neural tissue will facilitate research into neural development, function, and disease processes, as well as translational drug screening in vitro. Other possible applications in patient-specific neural tissue engineering for CNS tissue replacement following acute traumatic injury and chronic degenerative disease are of clinical nature. Defined patterning achieved 3D stem cell bioprinting has an interesting application in brain and neural tissue cancer research. Chemotherapy drug resistance is a known challenge in brain tumors, largely due to brain tumor stem cells, and thus researching brain tumor stem cell biology using in vitro constructs that recapitulate the native tumor tissue microenvironment has potential to improve current therapeutic regimens and develop novel treatments. Such 3D bioprinted tumor models can also allow for replication of patients’ tumors in vitro, to allow for personalization of therapies and individualized tumor testing for drug resistance and susceptibility.

3D bioprinting of Hepatic tissue

Fabrication of liver tissue constructs and organs has uses in regenerative medicine, especially given the acute need for livers and the limited numbers of viable donors. The creation of functional hepatic tissue also has applications in personalized in vitro drug screening and liver disease studies, as the liver is one of the main sites for drug processing and excretion.

Sacks and colleagues (JAMA 2014) evaluated clinical drug trials between 2000 and 2012 and reported that lack of efficacy alone accounted for only 41% of failures, while the combination of poor efficacy and safety accounted for 35%, and safety alone accounted for 19% of drug failures in the US market. Together, cardiovascular and liver toxicity accounted for nearly 75% of all post market drug withdrawals in the United States between 1975 and 2007. Cardiotoxicity seems to have surpassed hepatotoxicity as the main organ toxicity ending clinical trials or causing postmarket drug withdrawal while hepatotoxicity has been the most frequent cause of drug product recalls between 1953 and 2014. Collectively, the inadequate concordance of laboratory animal drug safety testing with human safety, the seeming limit of success with computational models to predict drug-induced clinical toxicity has shifted the focus to humanizing 3D microfluidic systems. Humanizing 3D constructs is possible with impregnating human sourced magic cells called stem cells that have the power to differentiate to hepatic cells and secrete liver organ related factors mimicking the very invivo system.

3D bioprinting of Adipose tissue

Fabrication of biomimetic 3D adipose tissue constructs that mimic the natural architecture of adipose tissue would not only allow for autologous tissue replacement but also for in vitro biomedical investigation of adipose tissue-related pathologies and in vitro drug screening. 

3D bioprinting of Skin

Bioprinted human skin for full-thickness defects, soft-tissue infection, trauma cases, tumor resection, and burn injuries is the next gen solution if for grafting.

There are a few 3D skin Organoids made out of human skin biopsies available as products in the global market for regulatory cosmetics testings. This is no better in terms of obtaining the raw material, referring to the painful biopsy procedure and the limitation with the quantity that can be sourced which can be looked as cruelty to donor. These are awesome advancements and mind boggling applications that are being developed with 3D printing technology in the past decade. If this technology is meant for human applications, without humanizing 3D prints., I see a disconnect with the entire concept. And when it comes to humanizing., human sourced bio materials (tissues, cells, exosomes like secreted factors) have to become part of integration. In any product development meant for real time application., the source material needs to be abundant and in this context., if bio materials., source cannot be biopsies or of cadaveric option for reasons obvious. The only viable or the best smart option here would be human sourced biological discards as starting material for harvesting the desired cell type. Now, in cell types as well., tissue specific cells will have limited life span and are known to be terminal in their growth at labs. So, the best opportunity as always is the stem cell type that has not only self renewing proliferating capacities, but also differentiation to other lineages to humanize 3D bioprints intended for the real applications.The crux is amalgamation of precise use of right kind of stem cells and 3D printing technology to offer great products in our life time.

 Transcell Oncologics offers primary human biological discards sourced characterized pluripotent stem cell based platforms as tools to integrate in 3D bioprinting technology intended for use in invitro toxicity testings.