Ethical considerations in tissue engineering research: Case studies in translation

Abstract

Tissue engineering research is a complex process that requires investigators to focus on the relationship between their research and anticipated gains in both knowledge and treatment improvements. The ethical considerations arising from tissue engineering research are similarly complex when addressing the translational progression from bench to bedside, and investigators in the field of tissue engineering act as moral agents at each step of their research along the translational pathway, from early benchwork and preclinical studies to clinical research. This review highlights the ethical considerations and challenges at each stage of research, by comparing issues surrounding two translational tissue engineering technologies: the bioartificial pancreas and a tissue engineered skeletal muscle construct. We present relevant ethical issues and questions to consider at each step along the translational pathway, from the basic science bench to preclinical research to first-in-human clinical trials. Topics at the bench level include maintaining data integrity, appropriate reporting and dissemination of results, and ensuring that studies are designed to yield results suitable for advancing research. Topics in preclinical research include the principle of “modest translational distance” and appropriate animal models. Topics in clinical research include key issues that arise in early-stage clinical trials, including selection of patient-subjects, disclosure of uncertainty, and defining success. The comparison of these two technologies and their ethical issues brings to light many challenges for translational tissue engineering research and provides guidance for investigators engaged in development of any tissue engineering technology.

Three-dimensional neuronal cell culture: in pursuit of novel treatments for neurodegenerative disease

“…[86][87][88] These involve questions related to the novelty of the technology itself, but also regarding its integration with biologic products (e.g. stem cell technology).…”

“…[87,88] Other factors worth to consider include data integrity and appropriate study design, which could prevent premature transition from the bench to the bedside stage. [86] This bedside stage, which involves clinical trials, predominantly addresses questions related to the participants; selection of participants, and most importantly, the risks for the participant, which should be appropriate compared with the potential benefits on the larger scale. Lastly, there are society-related ethical considerations, which include the public's perception of the biofabrication field.…”

Tissue Engineering Applications in Medicine

“…It is important to realize that, at any stage, the results of well-designed and properly conducted research might not lead forward, but back or in a different direction than expected. It is also important to refine and expand knowledge at an earlier stage of the research or to explore and develop newly identified possibilities [4].…”

“…The choice of animal models and their humane and appropriate use helps to ensure that the research transition from animals to humans adheres to principle of "modest translational distance" described by Jonathan Kimmerlman. Translational distance (TD) refers to the number and size of inferential loops from animals to humans-in other words, it measures uncertainty [4]. In order to move from preclinical to first-in-human and other early stage trials, several questions must be answered in the affirmative [4]:…”

“…Translational distance (TD) refers to the number and size of inferential loops from animals to humans-in other words, it measures uncertainty [4]. In order to move from preclinical to first-in-human and other early stage trials, several questions must be answered in the affirmative [4]:…”