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allowing donors to withdraw or update authorization at any development process, which may ultimately result in
time. At the same time, a new strong regulatory framework diagnostic tools, therapeutic products, or biomaterials of
is needed to ensure the autonomy of donors. At present, significant value, potentially generating enormous profits.
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countries are promoting special legislation for organoid Ensuring a balance between the interests of clinical
research and clarifying the bottom-line rules for informed donors providing biological samples, research institutions
consent, data use, and commercial transformation. investing intelligence and resources, and investors taking
risks to provide funding is a key issue in the equitable
Second, although organoids perform well in vitro, their
functional integrity and maturity still differ significantly distribution of the enormous benefits of these commercial
transformations. There is an urgent need to explore
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from human organs. The survival, integration, and innovative governance models and protocol frameworks
functional recovery of organoids after transplantation that meet basic ethical licensing requirements. A dynamic
into the body lack systematic verification. To overcome and sustainable balance needs to be found between
this challenge, the simplest approach is to first validate adequately incentivizing scientific and technological
organoids in animal models. Verifying the ability of innovation and ensuring that the technological dividend
organoids to integrate with host tissues and assessing their reaches society at large.
feasibility as potential transplants is crucial. However, the
implantation of human-derived organoids into animal 6. Construction techniques of next-
models raises deep cross-species ethical concerns. 267,268 generation organoids
When human tissues are highly developed in animals and
may even partially participate in or influence host MSK 6.1. Organoid-on-a-chip
functions, traditional species boundaries are substantially Organoid-on-a-chip, a multi-channel 3D microfluidic
impacted. This not only challenges existing biological platform recapitulating organ-level activities,
perceptions and socio-ethical concepts but may also raise biomechanical properties, and physiological responses,
profound questions about animal welfare and potentially will bring a revolutionary breakthrough in the cultivation
uncontrollable biological risks. Therefore, the development and application of MSK organoids. Its key strength lies
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of detailed and rigorous ethical review guidelines specific to in enabling continuous perfusion and dynamic medium
organoid chimera research has become an urgent scientific renewal through integrated microchannel networks,
and ethical task. Transplanting organoids back into the thereby overcoming the inherent limitations of conventional
human body to repair damaged tissue is arguably the static cultures. 273,274 This biomimetic fluid environment
ultimate goal of research, but it also faces high-risk ethical is crucial for metabolically demanding sports tissues,
considerations unique to human trials. Although preclinical especially skeletal MSK organoids that consume large
studies provide fundamental data, the unknowns of human amounts of oxygen and glucose and produce lactic acid.
transplantation remain enormous. Issues such as immune For instance, Kesharwani et al. used organoids derived
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rejection and long-term safety cannot be guaranteed. from human ESCs to model vascular dynamics at the initial
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Therefore, the ethical review system must play a crucial stage of endochondral ossification on a microfluidic chip.
role in centering on the strict application of the principle This model not only elucidates novel aspects of human
of risk minimization. This requires an extremely rigorous endochondral ossification but also demonstrates broad
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assessment of the trial design, including the selection of the application prospects for modeling bone disease and drug
most appropriate group of subjects, the setting of clear and screening. Another study conducted by Whelan et al.
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monitorable safety endpoints, the formulation of detailed established a microphysiological model of vascular invasion
contingency plans, and the establishment of a long-term during bone development and regeneration to recapitulate
follow-up mechanism. This ensures that the life safety and endochondral ossification. This process was achieved by
health rights of the subjects are prioritized to the highest integrating ECs with organoids representing distinct stages
degree. of endochondral bone development within a microfluidic
Finally, the rapid development of organoid technology chip.
has generated a huge commercial wave, which cannot be More importantly, OoC empowers researchers with
separated from issues of cost and benefit. Although the unprecedented spatiotemporal precision manipulation
combination of iPSCs and gene editing technology can of the experimental microenvironment. By integrating a
achieve individualized modeling of organoids, the high sophisticated flow control system, growth factors or drug
cost and long cycle of the technology mean that MSK molecules can be precisely applied to organoids at preset
organoids can currently only be developed on a small spatial and temporal points. 276,277 This capability enables
scale in laboratories and are unlikely to be widely adopted in vitro recapitulation of complex dynamic signaling
throughout society in the short term. In addition, cell cascades in MSK organoids, thereby modeling in vivo
samples from patients undergo a complex research and developmental, reparative, or pathological processes.

Volume 1 Issue 3 (2025) 22 doi: 10.36922/OR025280024