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International Journal of Bioprinting                                        Printed organoids for medicine




            derived organoids has revolutionized precision medicine   screening allows real-time evaluation of barrier integrity
            by facilitating the creation of personalized disease models   under pharmacological challenges, offering a scalable
            and advancing therapeutic research. 98,103  By incorporating   tool for drug permeability and toxicity studies. Similarly,
            immune cells, stromal cells, and other pertinent cell   Jonathan et al.  have developed the BATE technique
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            types as well as vascular networks into organoid models,   to create centimeter-sized gastrointestinal tissues with
            the ability to embed organoids within customizable   self-organizing features, enhancing the scalability and
            bioprinted geometries allows researchers to simulate the   applicability of bioprinted organoids in various research
            spatial heterogeneity of inflammatory microenvironments,   areas.  By merging microstructural fidelity with functional
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            including immune cell infiltration and cytokine gradients,   compartmentalization, these approaches transcend the
            and delve into the exploration of disease mechanisms, such   limitations of traditional models.  Their scalability and
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            as the impact of specific genes and signaling pathways in   adaptability pave the way for advanced intestinal niches
            inflammation, and facilitate the screening of potential   incorporating  dynamic  cues  or  microbial  interactions,
            therapeutic interventions. 106,107  Bioprinted organoids offer   promising  transformative  applications  in  drug  discovery
            valuable  insights into  the  pathogenesis  of  rheumatoid   and gut pathophysiology research.
            arthritis, characterized by persistent joint inflammation
            and  cartilage  degradation.  By  mimicking  interactions   3.2. Genetic diseases
            between synovial tissue and immune cells, these models   Genetic  disorders such as cystic fibrosis and hereditary
            facilitate the investigation of inflammatory mediators   metabolic defects have been modeled using bioprinted
            and genetic determinants. Furthermore, they enhance the   organoids  derived  from  iPSCs.  Bioprinting  enables  the
            optimization of pharmacological interventions that target   precise arrangement of wild-type and mutant cells within
            inflammatory pathways, holding promise for personalized   organoids, facilitating the analysis of cell-autonomous versus
            medicine.                                          non-cell-autonomous disease mechanisms. Human iPSC-
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                                                               derived neural organoids with patterned differentiation
               Intestinal organoids incorporating patient-derived   have been used to study neurodevelopmental disorders
            cells have been leveraged to study gut inflammation   caused by genetic mutations.  Organoids offer valuable
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            and epithelial barrier dysfunction, providing insights   insights into the cellular mechanisms involved in such
            into  inflammatory  bowel  disease  pathogenesis. 109,110   3D   disorders and the effectiveness of gene editing tools such
            bioprinting is notably applied in generating gastrointestinal   as CRISPR/Cas9 for potential therapeutic applications.
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            organoids, which demonstrate distinctive transcriptomic   The integration of CRISPR genome editing techniques
            and secretomic signatures in patients with Crohn’s   (including knockout, base editing, and prime editing) with
            disease, elucidating disease-specific mechanisms and   3D organoid cultures has enabled the modeling of disease
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            responses.  The quest to replicate the small intestine’s   progression and  the investigation  of genetic  disorders.
            intricate  architecture  and  physiology  in vitro  has driven   This approach effectively bridges the gap between patient-
            innovations  in  3D  bioprinting.  Conventional  planar   derived cells and our understanding of diseases.  Schene
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            epithelial monolayers lack the 3D villi topography   et al.  demonstrated the utility of prime editing in
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            essential for mimicking native absorption and barrier   repairing genetic defects within patient-derived organoids,
            dynamics. Stereolithographic 3D printing now addresses   showcasing the precision and therapeutic potential of this
            this gap through THE precision fabrication of villus-like   gene editing strategy.  Leigh syndrome, an untreatable
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            micropillar arrays using tunable poly(ethylene glycol)   mitochondrial disorder associated with a  SURF1
            diacrylate hydrogels.  These scaffolds sustain month-  mutation, has been addressed using Cas9 genome editing
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            long Caco-2 cultures, inducing apicobasal polarization   to rectify the mutated  SURF1 gene in patient-derived
            akin to in vivo epithelial organization, which serves as a   organoids.  This approach has provided insights into
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            critical advance for physiologically relevant transport   the  physiological  correlation between  SURF1 and  Leigh
            and metabolic studies (Figure 5A). A key innovation   syndrome. Additionally, patient-specific iPSCs have been
            lies  in dual-material  printing strategies that integrate   utilized to replicate macrocephaly/autism  phenotypes,
            diffusion-open villus microstructures with diffusion-  demonstrating the adaptability of patient-derived
            closed hydrogel walls. This compartmentalization isolates   organoids in investigating intricate genetic conditions.
            epithelial transport processes, emulating the luminal-  Furthermore, the CRISPR-Cas9 system has been employed
            interstitial interface while enabling high-throughput   in brain organoid models to induce models of congenital
            analysis. Functionally, Caco-2 cells on these platforms   nervous system malformation diseases, facilitating the
            form confluent barriers with tight junctions, validated by   exploration of these intricate disorders. 119,120  Additionally,
            transepithelial electrical resistance and fluorescent tracer   bone organoids bioprinted with GelMA bioinks have
            assays (Figure 5B). The compatibility with compound   replicated genetic bone disorders, like osteogenesis


            Volume 11 Issue 4 (2025)                        77                            doi: 10.36922/IJB025190184
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