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International Journal of Bioprinting                                        Printed organoids for medicine




            imperfecta, characterized by brittle bones, enabling the   and lupus-related vasculopathy. 39,125  Parallel advancements
            study of mutations in collagen-producing genes and their   in psoriatic modeling have been achieved through laser-
            impact on bone structure and strength.             assisted bioprinting of stratified skin organoids by Michael
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                                                               et al.  Their multilayered architecture, incorporating
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            3.3. Metabolic diseases                            patient-derived keratinocytes, fibroblasts, and immune
            Metabolic diseases, including diabetes and non-alcoholic   cells, recapitulated hallmarks of disease pathogenesis,
            fatty liver disease, have been modeled using bioprinted   including hyperproliferative epidermis, interleukin-23/
            hepatic and pancreatic organoids. Bioprinted liver   interleukin-17 axis dysregulation, and T-cell infiltration
            organoids with perfusable vascular networks mimic the   dynamics visualized via integrated microfluidics. 127,128  The
            zonated  metabolism  of  hepatocytes,  enabling  the  study   platform’s dual utility in mechanistic interrogation and
            of lipid accumulation and insulin resistance.  Recent   therapeutic screening was evidenced by the successful
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            advances in nozzle-free bioprinting have preserved   suppression  of  inflammatory  markers  using  anti-tumor
            organoid  polarization  and  liver-specific  enzyme  activity,   necrosis factor alpha biologics.  Nevertheless, the
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            which are critical for replicating metabolic dysfunction.    absence of neural components limits its capacity to model
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            Breakthroughs in bioprinted pancreatic organoids have   neuroimmune crosstalk, which is particularly relevant to
            demonstrated transformative potential for diabetes   pruritus mechanisms.  Future iterations incorporating
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            research and β-cell regeneration. A seminal study by Ahn    sensory neurons and Schwann cells could bridge this gap,
            et al.  has achieved functional restoration in diabetic   enabling a comprehensive study of itch pathways while
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            murine models through extrusion-based bioprinting   preserving the strength in real-time immune monitoring
            of  human   iPSC-derived  β-cells  co-encapsulated  and high-content drug evaluation.
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            with endothelial progenitors in a tunable alginate
            matrix. These constructs exhibited glucose-responsive   Additionally,  lymph  node  organoids  with  spatially
            insulin secretion and sustained normoglycemia post-  organized stromal and immune cell populations provide
            implantation, attributed to the integration of pre-vascular   platforms to investigate antigen presentation and T-cell
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            networks via co-printed endothelial cells. This enabled   activation in  autoimmune contexts.   The  translational
            perfusable microvasculature formation within 7 days   challenge for immune organoid research lies in
            and  an  immunoprotective  hydrogel  design  balancing   modeling sensitivity and resistance to immunotherapies,
            crosslinking density to permit metabolic exchange while   encompassing checkpoint inhibition, novel pathways,
            evading immune detection.  Furthermore, vascularized   and adoptive cell transfer strategies. The identification of
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            pancreatic  organoids have  been  employed to  investigate   underlying resistance pathways also holds considerable
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            β-cell dysfunction and insulin secretion dynamics under   promise for human tumor immunotherapy.  Together,
            hyperglycemic conditions.  Bone/cartilage organoids   these studies exemplify how spatial precision in bioprinting
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            enable the study of metabolic pathways in cartilage   accelerates both disease deconstruction and regenerative
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            development and pathologies. Analyzing the metabolomic   strategy  development.  Furthermore,  combining
            profiles of these organoids reveals insights into metabolic   organoids with advanced imaging techniques and multi-
            changes linked to conditions such as OA. Understanding   omics approaches can enhance our understanding of
            these alterations is vital for designing therapies targeting   immune responses and disease progression, paving the
            specific  metabolic  pathways  to  manage  cartilage   way for more effective therapeutic interventions.
            degradation. Integrating metabolomics with organoid   While significant progress has been made in modeling
            technology offers new research opportunities in bone   metabolic and immune diseases using bioprinted
            and cartilage biology, disease mechanisms, biomaterials,   organoids, further research is needed to overcome
            and  pharmacology.  This  approach  lays  the  groundwork   technical challenges and translate these models into
            for future research utilizing metabolomics for enhanced   clinical applications. The integration of organ-on-a-chip
            diagnostics, treatments, and regenerative approaches. 124  technology with metabolomics and advanced imaging
                                                               techniques will undoubtedly continue to drive innovation
            3.4. Immune diseases                               in disease modeling and therapy development.
            Bioprinted organoids  are  increasingly  used  to  model
            autoimmune and immune-mediated disorders. The      3.5. Neurodegenerative diseases
            incorporation of endothelial and immune cells into   Neurodegenerative disorders such as Alzheimer’s and
            bioprinted constructs allows the recapitulation of immune   Parkinson’s diseases have been modeled using bioprinted
            cell trafficking and vascular inflammation. 123,125  For   neural organoids. Multi-material bioprinting of human
            example, vascularized skin organoids with hierarchical   iPSC-derived neural stem cells and endothelial progenitors
            structures have been developed to study dermatological   has generated cortical organoids with layered regions and


            Volume 11 Issue 4 (2025)                        79                            doi: 10.36922/IJB025190184
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