Natural & Synthetic Supporting Structures for the Facilitated Perfusion of Granular Hydrogel Constructs; Ethical Issues Governing the Regulation of Tissue Engineering and Bioprinting Technologies
Armenta, Andres, School of Engineering and Applied Science, University of Virginia
Highley, Chris, EN-Biomed Engr Dept, University of Virginia
Earle, Joshua, EN-Engineering and Society, University of Virginia
Demand for human organs used in clinical applications such as transplantation, drug discovery, and disease modeling continues to increase. To alleviate this, the field of tissue engineering seeks to create viable organs which can be used for biomedical experimentation or as therapeutic solutions following implantation. However, a major challenge in the development of laboratory-grown tissues is the need to incorporate nutrient-supplying vessels, or vasculature, throughout tissues in order to keep embedded cells alive. In order to provide both in-vitro and in-vivo platforms for engineered tissue vascularization, the technical aspect of this project seeks to (1) create easily-reproducible devices for perfusing engineered tissues in the laboratory and (2) chemically integrate biomaterials into a single, suturable tissue construct for vessel anastomosis. In addition to technical limitations, effective tissue engineering technologies also face obstacles during clinical translation due to inadequate and non-specific regulatory policies. In pursuit of a thorough description and analysis of the regulatory landscape applied on tissue engineering technologies, the socio-technical analysis component of this work accumulates regulatory practices, guidelines, and policies from various governing bodies and countries. Furthermore, this analysis, in conjunction with the Responsible Research and Innovation (RRI) socio-technical framework, is used to propose improvements for the regulation of the tissue engineering field.
The subsequent technical report focuses on the development of technologies for supporting engineered tissue perfusion both in-vitro and in-vivo. In order to maintain the viability of living tissues in a laboratory setting, constant perfusion of vascular networks is necessary in order to provide nutrients for cells throughout the entirety of the tissues. This can be accomplished by encapsulating engineered tissues within perfusion devices which provide these tissues with both physical support and a connection to sources of fluid flow. The device created in this project seeks to satisfy these standard characteristics of perfusion devices, while simultaneously being created with affordable materials and accessible manufacturing techniques. To achieve this, extrusion-based three-dimensional printing of the synthetic and biocompatible material polydimethylsiloxane (PDMS) was utilized. The final perfusion chamber produced was successful in enabling fluid flow through a millimeter-scale biomaterial system, and showcases facile reproducibility through 3D printing techniques.
Because the final purpose of various tissue engineering products is the replacement of diseased tissue through patient implantation, processes for linking engineered tissues to host blood vessels are essential. Hydrogels can provide a highly tunable, hydrated, and biocompatible environment for cell growth. Moreover, hydrogel microparticles (HMPs) introduce increased porosity when compared to bulk hydrogels which further enhances cell migration and proliferation. Despite this, hydrogel materials do not contain the requisite mechanical properties for physical linkage to host tissues, such as through suturing. However, decellularized biological tissues, which retain much of the native extracellular matrix, may exhibit the physical robustness to tolerate clinically-applicable suturing techniques. Towards the goal of establishing a process for in-vivo perfusion, the binding of HMPs and decellularized porcine tissue into a singular, suturable construct was investigated.
Despite the rapid progression of the tissue engineering field, the evolution of regulatory pathways that can effectively evaluate these technologies is lacking. Not only does insufficient regulation complicate the translation of tissue engineering products into the clinic, but it also risks the inadequate assessment of ethical issues characteristic of the tissue engineering field. Various science, technology, and society (STS) frameworks have been developed which can provide insights into the interactions between complex technologies and human society. Responsible Research and Innovation is particularly useful for this work because it focuses on values which are deemed important for cutting-edge scientific developments, such as those within tissue engineering research. In order to provide greater insight and future directions for regulatory norms applied unto the tissue engineering field, this STS research analyzed a variety of regulatory pathways on a global scale using RRI as a foundation for determining the adequacy of regulatory policies.
BS (Bachelor of Science)
Tissue Engineering, Hydrogels, 3D Printing, Microgels, Responsible Research and Innovation, Regulation, Bioprinting, Ethics
School of Engineering and Applied Science
Bachelor of Science in Biomedical Engineering
Technical Advisor: Christopher Highley, Ph.D.
STS Advisor: Joshua Earle, Ph.D.
Technical Team Members: Bao Nguyen
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