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Innovative Medicines & Omics Biocompatibility of nanomaterials

a “protein corona” that changes its biological response. To better simulate physiological conditions, advanced
Uncontrolled corona formation may lead to unpredictable systems such as 3D cultures and co-culture platforms are
pharmacokinetics or off-target effects. Researchers have increasingly used. These models provide insights into
shown that tweaking surface energy can help control corona how nanoparticles affect cell signaling, differentiation,
composition, thereby guiding biological interactions in a and inflammatory pathways in environments that more
way that supports therapeutic goals. 18 closely mimic actual tissue architecture. While in vitro
methods offer speed, scalability, and cost-efficiency, they
Finally, the intrinsic nature of the nanomaterial itself
matters. Organic nanomaterials, such as liposomes or remain limited in representing the full complexity of a
polymers, are generally safer because the body naturally living organism. This limitation highlights the need for
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breaks them down. They are often preferred for treatments complementary in vivo evaluations.
requiring repeat dosing or prolonged systemic exposure. In 3.2. In vivo methods
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contrast, inorganic nanomaterials such as silica or gold may
be preferred for their strength or imaging capabilities, but they In vivo testing remains a cornerstone of biocompatibility
often need to be coated or encapsulated to ensure safety. This assessment, particularly for assessing systemic distribution,
is especially important in antiviral applications, where precise metabolism, excretion, and long-term toxicity. Animal
control over surface charge and hydrophilicity is required to models—especially rodents—enable comprehensive
avoid immune activation while preserving efficacy. 19 monitoring of biological responses at the organismal level,
including immune responses, hematological changes, and
3. Methodologies for biocompatibility potential organ-specific adverse effects. 22
assessment A practical example involves the implantation of CaO

Assessing the biocompatibility of nanomaterials and CaP nanocomposite scaffolds in rat bone defects. Our
involves a multidisciplinary framework, incorporating ongoing in vivo studies demonstrated not only effective
laboratory assays, animal studies, computational tools, tissue regeneration but also favorable immune modulation
and regulatory evaluation. This integrated approach is at the site of implantation. Histopathological analysis, a
essential to understand the complex interactions between key component of in vivo assessments, helped detect subtle
nanomaterials and biological systems, ensuring both tissue-level reactions such as fibrosis and inflammation.
safety and efficacy for clinical translation. As nano–bio Kyriakides et al. further highlighted the value of in vivo
interactions vary depending on material properties and testing in revealing immunological changes such as
intended application, using a combination of assessment cytokine production and complement activation, offering
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methods helps to identify and mitigate potential risks early critical insights into nanomaterial-host interactions.
in the development process. Despite their utility, in vivo models face limitations
due to ethical concerns, regulatory scrutiny, and species-
3.1. In vitro methods to-species differences, which complicate the extrapolation
In vitro techniques are typically the first step in evaluating of animal data to human contexts. To address these
the biological compatibility of nanomaterials. These cell- challenges, alternative platforms—such as organ-on-chip
based assays offer a controlled environment to investigate devices and ex vivo perfusion systems—are being explored
how nanoparticles influence cellular health, behavior, as more ethically sound and potentially more predictive
and morphology. Standard protocols include MTT and options. 22
resazurin reduction assays, which assess metabolic activity,
along with tests for membrane disruption, oxidative stress, 3.3. Computational models
and programmed cell death. 19 Computational modeling provides a predictive layer to

For example, Siller et al. introduced a real-time biocompatibility evaluation using simulations and data-
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live-cell imaging system that continuously monitors driven algorithms to estimate biological interactions.
the cytotoxicity and morphology of cells in response to Molecular dynamics simulations, for example, allow
3D-printed biomaterials. This approach enables high- scientists to explore how nanoparticles interact with
throughput analysis with temporal resolution. Similarly, cellular membranes or proteins at the atomic level, helping
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Wang et al. explored the biosynthesis of zinc oxide to anticipate toxic effects before physical experimentation.
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nanoparticles using plant extracts and evaluated their Cao et al. demonstrated the utility of computational
effect on human osteoblast-like cells. The MTT assay tools such as nano-quantitative structure–activity
results indicated improved cell proliferation and bone- relationship models to estimate the toxicity of metal oxide
forming potential. nanoparticles. By analyzing properties such as surface

Volume 2 Issue 3 (2025) 47 doi: 10.36922/IMO025210024