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International Journal of Bioprinting Bioprinted skin for testing of therapeutics
produce their own ECM (Figure 5) in an autologous setting. Project 103597 (Novel manufacture and commercialization
The resulting skin equivalents were comparable to healthy of a 96-well 3D skin model for drug and toxicology testing).
human skin (Figure 6) and could be co-cultured with
PBMCs to produce a fully autologous assay with automated Conflict of interest
deposition of cells, which is scalable to commercial demand. The authors declare no conflicts of interest.
The biologically inert scaffold-based approach allows the
formation of a fully autologous human skin equivalent. Author contributions
The bioprinting of viable and functional human cells using
solenoid microvalves circumvents the labor-intensive aspect Conceptualization: Kenneth Dalgarno, Anne Dickinson,
of creating 96-well tissue constructs on a large scale. This Stefan Przyborski
method enables the production of biologically representative Investigation: Mahid Ahmed
and functional HSEs that may be developed in a scalable Methodology: David Hill, Shaheda Ahmed
manner. This approach could potentially be applied to wider Formal analysis: Mahid Ahmed, David Hill, Shaheda Ahmed
applications such as disease modeling and modeling of Writing – original draft: Mahid Ahmed, Kenneth Dalgarno,
wound healing, and one specific aspect of future work will Anne Dickinson
involve innervating the 3D skin model using neuronal and Writing – review & editing: David Hill, Kenneth Dalgarno,
Swann cells lines in order to further validate the model and Anne Dickinson, Stefan Przyborski
assess pain-relieving drugs. In terms of development and
use of human skin equivalents, this method of biofabrication Ethics approval and consent to participate
produces a human skin equivalent that provides a potential Skin cells were obtained from healthy volunteers, with
alternative to non-animal testing and avoids cross-species ethical approval for the procedure from Newcastle
reactivity, which can impact data interpretation. and North Tyne 1 Research Ethics Committee,
REC 10/H0906/58.
5. Conclusion
Consent for publication
This study successfully demonstrated that solenoid
microvalve-based bioprinting of autologous skin Not applicable.
equivalents in a 96-well format could be used to determine
adverse immune responses of monoclonal antibodies in the Availability of data
human setting. Primary human skin cells were shown to be Data can be obtained from the
viable post printing and were shown to retain the functional Newcastle University Open Data Archive
capabilities required of the cells to generate human skin (https://doi.org/10.25405/data.ncl.24566740.v1).
equivalents. The co-culture of autologous bioprinted skin
equivalents with autologous PBMCs successfully identified References
adverse immune reactions of positive and negative
therapeutic antibodies, respectively. Overall, this study has 1. Stebbings R, Findlay L, Edwards C, et al. “Cytokine storm”
demonstrated that bioprinted human tissue can identify in the phase I trial of monoclonal antibody TGN1412: better
in vitro adverse immune responses triggered by therapeutic understanding the causes to improve preclinical testing of
antibodies. The scalability of both the Alvetex inserts and immunotherapeutics. J Immunol. 2007;179(5):3325-3331.
the bioprinting approach means that in combination these doi: 10.4049/jimmunol.179.5.3325
technologies are able to produce human skin equivalents at 2. Hay M, Thomas D, Craighead J, Economides C, Rosenthal J.
high-throughput rates, enhancing pre-clinical evaluation Clinical development success rates for investigational drugs.
of novel biologics prior to clinical testing. Nat Biotechnol. 2014;32:40-51.
doi: 10.1038/nbt.2786
Acknowledgments 3. Pound P, Ritskes-Hoitinga M. Is it possible to overcome
None. issues of external validity in preclinical animal research?
Why most animal models are bound to fail. J Transl Med.
2018;16:304.
Funding doi: 10.1186/s12967-018-1678-1
This research was supported by the EPSRC Centre for 4. Panoskaltsis N, McCarthy NE, Knight SC. Myelopoiesis of
Doctoral Training in Additive Manufacturing and 3D acute inflammation: lessons from TGN1412-induced cytokine
Printing (EP/L01534X/1), and by Innovate UK through storm. Cancer Immunol Immunother. 2021;70:1155-1160.
Volume 10 Issue 2 (2024) 486 doi: 10.36922/ijb.1851

