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Animal-Free Hydrogels: Building the Future of Predictive, Ethical Drug Discovery

  • Viola Erdelyi
  • 32 minutes ago
  • 6 min read

Despite all the scientific breakthroughs behind modern drug development, one less than ideal truth remains: current preclinical models are failing us. Nearly 90% of drugs entering clinical trials never make it to patients, most commonly because they don’t work as expected in humans or cause unexpected toxicity [1]. This staggering attrition rate highlights a fundamental issue with animal-derived products that are used in basic science. Namely, that they respond very differently to drug treatment.


For decades, researchers have relied on 2D cell cultures and animal models to evaluate drug safety and efficacy, but these systems often fall short of representing true human biology. As a result, promising candidates frequently advance based on false positive data, only to fail later at enormous scientific, financial, and ethical cost.


Today, however, a new shift is underway. Driven by scientific innovation and regulatory change, animal-free, human-relevant models are emerging as credible alternatives. Among these, synthetic hydrogels are proving to be some of the most exciting tools in the next generation of drug discovery.



Why animal-free NAMs are becoming the new standard


With the move toward New Approach Methodologies (NAMs), non-animal, human-focused testing systems is accelerating worldwide. This shift is not just a ‘nice to have’ it is now supported by policy.


In the United States, the FDA Modernization Act 2.0 has opened the door for non-animal data to be used for advancing drugs to clinical trials, eliminating the decades-old assumption that animal testing is the “gold standard.” Similarly, the UK Government’s 2025 Strategy for Replacing Animals in Science outlines a clear commitment to support and adopt validated alternatives across research, drug development, and regulatory science.


These policy milestones reflect a growing recognition that human-specific models are not only more ethical, but they’re also more relevant, reliable and reproducible. With the thorough research, we can generate data that more accurately predicts how a drug will behave in people. And this is where synthetic hydrogels stand out.



State-of-the-art: Synthetic hydrogels such as PeptiMatrix


Hydrogels are water-rich, three-dimensional polymer networks that mimic essential features of human extracellular matrix (ECM). Unlike animal-derived matrices such as Matrigel or collagen, synthetic hydrogels offer:

  • fully defined composition

  • excellent batch-to-batch reproducibility

  • tuneable stiffness

  • compatibility with a wide range of human cell types

  • alignment with ethical, sustainable, and regulatory expectations

Here at PeptiMatrix, we are working hard to provide a product that has the tunability and compatibility with static culture, perfusion systems, and organ-on-chip devices, etc. to further cutting-edge science. These next-generation hydrogels allow researchers to re-create human-like microenvironments in vitro, improving the physiological relevance of drug testing and disease modelling.

 


Case Study 1 : A 3D peptide hydrogel model for AML drug screening


A recent study demonstrated the power of synthetic hydrogels by developing a self-assembling peptide-based system that mimics features of the bone-marrow niche. Acute myeloid leukaemia (AML) cell lines, as well as primary leukemic cells, not only survived but formed colonies within this 3D environment [2].


The real highlight of the study was that it showed that FDA-approved drugs can be repurposed for the treatment of AML. Two compounds, Salinomycin and Atorvastatin, significantly reduced AML cell growth, consistent with potential benefit, while another candidate, Vidofludimus, showed minimal impact.



Figure of candidate drug efficacy of THP-1 cells encapsulated in gells

Figure 5. Candidate drug efficacy of THP-1 cells encapsulated in 6 mg/mL self-assembling peptide hydrogel (SAPH). (A) Bar graphs displaying the percentage survival of treated THP-1 cells 72 h after drug addition to ‘early-stage’ SAPH models. (B) Bar graphs displaying the percentage survival of treated THP-1 cells 72 h after drug addition in ‘established’ SAPH models. For all results, mean values ± standard deviation of biological replicates (N = 3, n = 3) are plotted throughout. Statistical significance (determined by two-way ANOVA in GraphPad Prism): p < 0.05, * p < 0.01, **** p < 0.0001. All results are presented as percentages compared to vehicle (DMSO) control of 0.02% for calculated EC50 values in liquid culture.



Case Study 2: Animal-free hydrogels for advanced liver toxicity models


Another recent study evaluated several fully animal-free hydrogels, including peptide-based and polysaccharide-based matrices, for their ability to support HepaRG liver cells under both traditional culture and in microphysiological flow systems [3].


All hydrogels supported cell viability and proliferation. However, PeptiMatrix at 7.5 mg/mL stood out, as it supported promising metabolic activity, suggesting that synthetic hydrogels could one day replace animal-derived matrices for advanced liver toxicity and metabolism studies.


Heatmap summarising the findings comparing tested animal-free hydrogels

Figure 8. Heatmap summarising the findings and comparing the tested alternative hydrogels with the Matrigel–collagen and gel-free mixtures under static (*) and dynamic culture conditions. Colour grading was used to compare the application considerations and biocompatibility aspects for creating viable and metabolically competent HepaRG cultures. The blank regions indicate that the corresponding categories were not applicable. The factors were evaluated by (i) reviewing the characteristics described in literature, (ii) injecting hydrogels into the OrganoPlate at different concentrations, (iii) assaying for viability and proliferation, (iv) staining for cell distribution and on-chip population, as well as (v) measuring the basal functions after in situ differentiation under both static and dynamic conditions.


While some functional endpoints still fell short of those achieved with animal-derived control matrices, the progress is nonetheless significant. With further refinement, these hydrogels could provide more reliable, ethical, and scalable solutions for preclinical toxicology, an area that has long relied on animal testing. Next-generation hydrogels now allow the incorporation of recombinant ECM components, creating well-defined and controllable matrices that eliminate the variability inherent to animal-derived materials. This increased control supports both reproducibility and predictive power, qualities that traditional animal-derived products fundamentally lack.



The road ahead: why the future looks bright


The convergence of materials science, stem cell biology, microfluidics, and regulatory innovation is accelerating the rise of animal-free systems. Over the next decade, we can expect:


  1. More sophisticated, tissue-specific hydrogels Incorporated ECM motifs, degradability, oxygen control — all designed to match human tissue architecture and function.


  2. Integration with organ-on-chip and microphysiological systems

    Hydrogels that interface seamlessly with perfused devices will enable realistic organ-level responses to drugs.


  3. Increased regulatory confidence and uptake

    As NAMs gain validation, pharmaceutical pipelines will adopt them earlier and more widely.


  4. More predictive toxicology and efficacy data

    Better preclinical relevance means fewer clinical failures — a win for patients, researchers, and industry.


  5. Reduction and eventual replacement of animal testing

    Driven by performance, economics, and policy support, synthetic hydrogels will play a central role in the transition.




Conclusion


The drug-development ecosystem is entering a pivotal shift. Synthetic, animal-free hydrogels, once niche materials, are now emerging as strategic technologies that can make drug discovery more predictive, more ethical, and more efficient.

As we refine these platforms and integrate them with cutting-edge NAMs, the vision becomes clear: a future where reliable human-specific models reduce the need for animal testing and significantly improve the success rate of new medicines. If you would like to join the pioneering group of scientists who have already made the switch to animal-free 3D models or if you would like to chat with us, please get in touch: info@peptimatrix.com

 


Get in touch!

If you'd like to learn more about these models or some of the other models we're currently building, feel free to reach out to: info@peptimatrix.com



About the author

Viola is cancer research scientist, who earned her PhD from the University of Nottingham. Her project focused on testing small-molecule SRPK1 and CLK1 inhibitors for the treatment of Acute Myeloid Leukaemia, as well as shedding light on alternative RNA splicing in the same disease, which could be detected through different isoform expressions of the BRD4 gene. She also gained significant experience working on humanised anti-VEGF165b antibodies whilst working in the Tumour Vascular Biology Lab (University of Nottingham) in collaboration with IsomAb Ltd.



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