Dong Gyu Hwang

All Publications

• Label-free mid-infrared dichroism-sensitive photoacoustic microscopy for histostructural analysis of engineered heart tissues. Light, science & applications Park, E., Hwang, D. G., Choi, H., Kim, D., Ahn, J., Lee, Y. J., Eom, T. J., Jang, J., Kim, C. 2026; 15 (1): 49

  Abstract

  Many biological tissues, such as cardiac muscle, tendons, and the cornea, exhibit highly organized microstructural alignment that is critical for mechanical and physiological functions. Disruptions in this structural organization are commonly associated with pathological conditions such as fibrosis, infarction, and cancer. However, conventional histological imaging techniques rely on immunofluorescence or histochemical staining, and they evaluate tissue alignment via non-physical 2D gradient-based calculation, which is labor-intensive, antibody-dependent, and prone to variability. Here, we demonstrate label-free mid-infrared dichroism-sensitive photoacoustic microscopy (MIR-DS-PAM), an analytical imaging system for cardiac tissue assessments. By combining molecular specificity with polarization sensitivity, this method selectively visualizes protein-rich engineered heart tissue (EHT) and quantifies the extracellular matrix (ECM) alignment without any labeling. The extracted dichroism-sensitive parameters, such as the degree of dichroism and the orientation angle, enable histostructural evaluation of tissue integrity and reveal diagnostic cues in fibrotic EHT. This technique offers a label-free analytical tool for fibrosis research and tissue engineering applications.

  View details for DOI 10.1038/s41377-025-02117-0

  View details for PubMedID 41484058

  View details for PubMedCentralID PMC12764944

• Bioprinting-Assisted Tissue Assembly to Investigate Endothelial Cell Contributions in Cardiac Fibrosis and Focal Fibrosis Modeling ADVANCED NANOBIOMED RESEARCH Hwang, D., Choi, H., Kim, M., Kim, M., Kim, D., Park, J., Jang, J. 2025; 5 (10)

  View details for DOI 10.1002/anbr.202400148

  View details for Web of Science ID 001500102400001

• Author Correction: Bioprinting of bespoke islet-specific niches to promote maturation of stem cell-derived islets. Nature communications Kim, M., Cho, S., Hwang, D. G., Shim, I. K., Kim, S. C., Jang, J., Jang, J. 2025; 16 (1): 2205

  View details for DOI 10.1038/s41467-025-57524-z

  View details for PubMedID 40044679

  View details for PubMedCentralID PMC11882978

• Bioprinting of bespoke islet-specific niches to promote maturation of stem cell-derived islets. Nature communications Kim, M., Cho, S., Hwang, D. G., Shim, I. K., Kim, S. C., Jang, J., Jang, J. 2025; 16 (1): 1430

  Abstract

  Pancreatic islets are densely packed cellular aggregates containing various hormonal cell types essential for blood glucose regulation. Interactions among these cells markedly affect the glucoregulatory functions of islets along with the surrounding niche and pancreatic tissue-specific geometrical organization. However, stem cell (SC)-derived islets generated in vitro often lack the three-dimensional extracellular microenvironment and peri-vasculature, which leads to the immaturity of SC-derived islets, reducing their ability to detect glucose fluctuations and insulin release. Here, we bioengineer the in vivo-like pancreatic niches by optimizing the combination of pancreatic tissue-specific extracellular matrix and basement membrane proteins and utilizing bioprinting-based geometrical guidance to recreate the spatial pattern of islet peripheries. The bioprinted islet-specific niche promotes coordinated interactions between islets and vasculature, supporting structural and functional features resembling native islets. Our strategy not only improves SC-derived islet functionality but also offers significant potential for advancing research on islet development, maturation, and diabetic disease modeling, with future implications for translational applications.

  View details for DOI 10.1038/s41467-025-56665-5

  View details for PubMedID 39920133

  View details for PubMedCentralID PMC11805982

• Bioprinting approaches in cardiac tissue engineering to reproduce blood-pumping heart function. iScience Kim, M., Hwang, D. G., Jang, J. 2025; 28 (1): 111664

  Abstract

  The heart, with its complex structural and functional characteristics, plays a critical role in sustaining life by pumping blood throughout the entire body to supply nutrients and oxygen. Engineered heart tissues have been introduced to reproduce heart functions to understand the pathophysiological properties of the heart and to test and develop potential therapeutics. Although numerous studies have been conducted in various fields to increase the functionality of heart tissue to be similar to reality, there are still many difficulties in reproducing the blood-pumping function of the heart. In this review, we discuss advancements in cells, biomaterials, and biofabrication in cardiac tissue engineering to achieve cardiac models that closely mimic the pumping function. Moreover, we provide insight into future directions by proposing future perspectives to overcome remaining challenges, such as scaling up and biomimetic patterning of blood vessels and nerves through bioprinting.

  View details for DOI 10.1016/j.isci.2024.111664

  View details for PubMedID 39868032

  View details for PubMedCentralID PMC11763539

• Unsupervised inter-domain transformation for virtually stained high-resolution mid-infrared photoacoustic microscopy using explainable deep learning. Nature communications Park, E., Misra, S., Hwang, D. G., Yoon, C., Ahn, J., Kim, D., Jang, J., Kim, C. 2024; 15 (1): 10892

  Abstract

  Mid-infrared photoacoustic microscopy can capture biochemical information without staining. However, the long mid-infrared optical wavelengths make the spatial resolution of photoacoustic microscopy significantly poorer than that of conventional confocal fluorescence microscopy. Here, we demonstrate an explainable deep learning-based unsupervised inter-domain transformation of low-resolution unlabeled mid-infrared photoacoustic microscopy images into confocal-like virtually fluorescence-stained high-resolution images. The explainable deep learning-based framework is proposed for this transformation, wherein an unsupervised generative adversarial network is primarily employed and then a saliency constraint is added for better explainability. We validate the performance of explainable deep learning-based mid-infrared photoacoustic microscopy by identifying cell nuclei and filamentous actins in cultured human cardiac fibroblasts and matching them with the corresponding CFM images. The XDL ensures similar saliency between the two domains, making the transformation process more stable and more reliable than existing networks. Our XDL-MIR-PAM enables label-free high-resolution duplexed cellular imaging, which can significantly benefit many research avenues in cell biology.

  View details for DOI 10.1038/s41467-024-55262-2

  View details for PubMedID 39738110

  View details for PubMedCentralID PMC11685655

• Engineering pore-enriched and pre-vascularized volumetric constructs for enhanced blood glucose regulation in type 1 diabetes therapy. Biofabrication Kim, J., Shim, I. K., Lee, Y. N., Kim, M., Hwang, D. G., Kim, J., Jo, Y., Chae, S., Kim, J., Kim, S. C., Cho, D. W., Jang, J. 2024; 17 (1)

  Abstract

  Managing type 1 diabetes mellitus (T1DM) presents significant challenges because of the complexity of replicating the microenvironment of pancreatic islets and ensuring the long-term viability and function of transplanted insulin-producing cells (IPCs). This study developed a functional approach that utilizes 3D bioprinting technology to create pore-enriched and pre-vascularized tissue constructs incorporating a pancreatic tissue-derived decellularized extracellular matrix and human-induced pluripotent stem cells (hiPSCs) aimed at enhancing blood glucose regulation in T1DM. We designed a volumetric 3D pancreatic tissue construct that supported the engraftment, survival, and insulin-producing functionality of hiPSC-derived IPCs. The construct's porosity was optimized to enhance IPC delivery efficiency. Additionally, human umbilical vein endothelial cells co-cultured with IPCs in a patterned structure facilitated pre-vascularization, improving construct integration with host tissues and accelerating revascularization post-transplantation. Our results demonstrate high cell viability and sustained insulin production in diabetic rodent models, indicating the constructs' effectiveness in regulating blood glucose levels over an extended period. The findings of this study not only underscore the potential of 3D bioprinting for creating functional tissue constructs for T1DM treatment but also offer efficient cell delivery techniques applicable to other areas of regenerative medicine.

  View details for DOI 10.1088/1758-5090/ad998e

  View details for PubMedID 39622163

• Biohybrid printing approaches for cardiac pathophysiological studies. Biosensors & bioelectronics Hwang, D. G., Kang, W., Park, S. M., Jang, J. 2024; 260: 116420

  Abstract

  Bioengineered hearts, which include single cardiomyocytes, engineered heart tissue, and chamber-like models, generate various biosignals, such as contractility, electrophysiological, and volume-pressure dynamic signals. Monitoring changes in these signals is crucial for understanding the mechanisms of disease progression and developing potential treatments. However, current methodologies face challenges in the continuous monitoring of bioengineered hearts over extended periods and typically require sacrificing the sample post-experiment, thereby limiting in-depth analysis. Thus, a biohybrid system consisting of living and nonliving components was developed. This system primarily features heart tissue alongside nonliving elements designed to support or comprehend its functionality. Biohybrid printing technology has simplified the creation of such systems and facilitated the development of various functional biohybrid systems capable of measuring or even regulating multiple functions, such as pacemakers, which demonstrates its versatility and potential applications. The future of biohybrid printing appears promising, with the ongoing exploration of its capabilities and potential directions for advancement.

  View details for DOI 10.1016/j.bios.2024.116420

  View details for PubMedID 38805890

• Bioprinting-Assisted Tissue Assembly for Structural and Functional Modulation of Engineered Heart Tissue Mimicking Left Ventricular Myocardial Fiber Orientation. Advanced materials (Deerfield Beach, Fla.) Hwang, D. G., Choi, H., Yong, U., Kim, D., Kang, W., Park, S. M., Jang, J. 2024; 36 (34): e2400364

  Abstract

  Left ventricular twist is influenced by the unique oriented structure of myocardial fibers. Replicating this intricate structural-functional relationship in an in vitro heart model remains challenging, mainly due to the difficulties in achieving a complex structure with synchrony between layers. This study introduces a novel approach through the utilization of bioprinting-assisted tissue assembly (BATA)-a synergistic integration of bioprinting and tissue assembly strategies. By flexibly manufacturing tissue modules and assembly platforms, BATA can create structures that traditional methods find difficult to achieve. This approach integrates engineered heart tissue (EHT) modules, each with intrinsic functional and structural characteristics, into a layered, multi-oriented tissue in a controlled manner. EHTs assembled in different orientations exhibit various contractile forces and electrical signal patterns. The BATA is capable of constructing complex myocardial fiber orientations within a chamber-like structure (MoCha). MoCha replicates the native cardiac architecture by exhibiting three layers and three alignment directions, and it reproduces the left ventricular twist by exhibiting synchronized contraction between layers and mimicking the native cardiac architecture. The potential of BATA extends to engineering tissues capable of constructing and functioning as complete organs on a large scale. This advancement holds the promise of realizing future organ-on-demand technology.

  View details for DOI 10.1002/adma.202400364

  View details for PubMedID 38717016

• Tissue-specific gelatin bioink as a rheology modifier for high printability and adjustable tissue properties. Biomaterials science Han, H., Kim, M., Yong, U., Jo, Y., Choi, Y. M., Kim, H. J., Hwang, D. G., Kang, D., Jang, J. 2024; 12 (10): 2599-2613

  Abstract

  Decellularized extracellular matrix (dECM) has emerged as an exceptional biomaterial that effectively recapitulates the native tissue microenvironment for enhanced regenerative potential. Although various dECM bioinks derived from different tissues have shown promising results, challenges persist in achieving high-resolution printing of flexible tissue constructs because of the inherent limitations of dECM's weak mechanical properties and poor printability. Attempts to enhance mechanical rigidity through chemical modifications, photoinitiators, and nanomaterial reinforcement have often compromised the bioactivity of dECM and mismatched the desired mechanical properties of target tissues. In response, this study proposes a novel method involving a tissue-specific rheological modifier, gelatinized dECM. This modifier autonomously enhances bioink modulus pre-printing, ensuring immediate and precise shape formation upon extrusion. The hybrid bioink with GeldECM undergoes a triple crosslinking system-physical entanglement for pre-printing, visible light photocrosslinking during printing for increased efficiency, and thermal crosslinking post-printing during tissue culture. A meticulous gelatinization process preserves the dECM protein components, and optimal hybrid ratios modify the mechanical properties, tailoring them to specific tissues. The application of this sequential multiple crosslinking designs successfully yielded soft yet resilient tissue constructs capable of withstanding vigorous agitation with high shape fidelity. This innovative method, founded on mechanical modulation by GeldECM, holds promise for the fabrication of flexible tissues with high resilience.

  View details for DOI 10.1039/d3bm02111d

  View details for PubMedID 38546094

• Biohybrid 3D Printing of a Tissue-Sensor Platform for Wireless, Real-Time, and Continuous Monitoring of Drug-Induced Cardiotoxicity. Advanced materials (Deerfield Beach, Fla.) Yong, U., Kim, D., Kim, H., Hwang, D. G., Cho, S., Nam, H., Kim, S., Kim, T., Jeong, U., Kim, K., Chung, W. K., Yeo, W. H., Jang, J. 2023; 35 (11): e2208983

  Abstract

  Drug-induced cardiotoxicity is regarded as a major hurdle in the early stages of drug development. Although there are various methods for preclinical cardiotoxicity tests, they cannot completely predict the cardiotoxic potential of a compound due to the lack of physiological relevance. Recently, 3D engineered heart tissue (EHT) has been used to investigate cardiac muscle functions as well as pharmacological effects by exhibiting physiological auxotonic contractions. However, there is still no adequate platform for continuous monitoring to test acute and chronic pharmacological effects in vitro. Here, a biohybrid 3D printing method for fabricating a tissue-sensor platform, composed of a bipillar-grafted strain gauge sensor and EHT, is first introduced. Two pillars are three-dimensionally printed as grafts onto a strain gauge-embedded substrate to promote the EHT contractility and guide the self-assembly of the EHTs along with the strain gauge. In addition, the integration of a wireless multi-channel electronic system allows for continuous monitoring of the EHT contractile force by the tissue-sensor platform and, ultimately, for the observation of the acute and chronic drug effects of cardiotoxicants. In summary, biohybrid 3D printing technology is expected to be a potential fabrication method to provide a next-generation tissue-sensor platform for an effective drug development process.

  View details for DOI 10.1002/adma.202208983

  View details for PubMedID 36528341

• Bioprinting-assisted tissue assembly to generate organ substitutes at scale. Trends in biotechnology Jo, Y., Hwang, D. G., Kim, M., Yong, U., Jang, J. 2023; 41 (1): 93-105

  Abstract

  Various external cues can guide cellular behavior and maturation during developmental processes. Recent studies on bioprinting-assisted tissue engineering have considered this a practical, versatile, and flexible way to provide external cues to developing engineered tissues. An ensemble of multiple external cues can improve the speed and capability of morphogenesis. In this review, we discuss how bioprinting and biomaterials provide multiple guidance to generate micro-sized building blocks with specific shapes and also highlight their applications in tissue assembly toward volumetric tissue and organ generation. Furthermore, we discuss our perspectives on the future translation of bioprinting technologies integrated with artificial intelligence (AI) and robot-assisted apparatus to promote automation, standardization, and clinical translation of bioprinted tissues.

  View details for DOI 10.1016/j.tibtech.2022.07.001

  View details for PubMedID 35907704

• Facile Bioprinting Process for Fabricating Size-Controllable Functional Microtissues Using Light-Activated Decellularized Extracellular Matrix-Based Bioinks ADVANCED MATERIALS TECHNOLOGIES Kang, B., Park, Y., Hwang, D., Kim, D., Yong, U., Lim, K. S., Jang, J. 2022; 7 (1)

  View details for DOI 10.1002/admt.202100947

  View details for Web of Science ID 000708697500001

• A 3D bioprinted hybrid encapsulation system for delivery of human pluripotent stem cell-derived pancreatic islet-like aggregates. Biofabrication Hwang, D. G., Jo, Y., Kim, M., Yong, U., Cho, S., Choi, Y. M., Kim, J., Jang, J. 2021; 14 (1)

  Abstract

  Islet transplantation is a promising treatment for type 1 diabetes. However, treatment failure can result from loss of functional cells associated with cell dispersion, low viability, and severe immune response. To overcome these limitations, various islet encapsulation approaches have been introduced. Among them, macroencapsulation offers the advantages of delivering and retrieving a large volume of islets in one system. In this study, we developed a hybrid encapsulation system composed of a macroporous polymer capsule with stagger-type membrane and assemblable structure, and a nanoporous decellularized extracellular matrix (dECM) hydrogel containing pancreatic islet-like aggregates using 3D bioprinting technique. The outer part (macroporous polymer capsule) was designed to have an interconnected porous architecture, which allows insulin-producingβ-cells encapsulated in the hybrid encapsulation system to maintain their cellular behaviors, including viability, cell proliferation, and insulin-producing function. The inner part (nanoporous dECM hydrogel), composed of the 3D biofabricated pancreatic islet-like aggregates, was simultaneously placed into the macroporous polymer capsule in one step. The developed hybrid encapsulation system exhibited biocompatibilityin vitroandin vivoin terms of M1 macrophage polarization. Furthermore, by controlling the printing parameters, we generated islet-like aggregates, improving cell viability and functionality. Moreover, the 3D bioprinted pancreatic islet-like aggregates exhibited structural maturation and functional enhancement associated with intercellular interaction occurring at theβ-cell edges. In addition, we also investigated the therapeutic potential of a hybrid encapsulation system by integrating human pluripotent stem cell-derived insulin-producing cells, which are promising to overcome the donor shortage problem. In summary, these results demonstrated that the 3D bioprinting approach facilitates the fabrication of a hybrid islet encapsulation system with multiple materials and potentially improves the clinical outcomes by driving structural maturation and functional improvement of cells.

  View details for DOI 10.1088/1758-5090/ac23ac

  View details for PubMedID 34479233

• Fabrication of an align-random distinct, heterogeneous nanofiber mat endowed with bifunctional properties for engineered 3D cardiac anisotropy COMPOSITES PART B-ENGINEERING Eom, S., Park, S., Hwang, D., Kim, H., Jang, J., Kim, D. 2021; 226

  View details for DOI 10.1016/j.compositesb.2021.109336

  View details for Web of Science ID 000704156500003

• 3D Bioprinting-Based Vascularized Tissue Models Mimicking Tissue-Specific Architecture and Pathophysiology for in vitro Studies. Frontiers in bioengineering and biotechnology Hwang, D. G., Choi, Y. M., Jang, J. 2021; 9: 685507

  Abstract

  A wide variety of experimental models including 2D cell cultures, model organisms, and 3D in vitro models have been developed to understand pathophysiological phenomena and assess the safety and efficacy of potential therapeutics. In this sense, 3D in vitro models are an intermediate between 2D cell cultures and animal models, as they adequately reproduce 3D microenvironments and human physiology while also being controllable and reproducible. Particularly, recent advances in 3D in vitro biomimicry models, which can produce complex cell structures, shapes, and arrangements, can more similarly reflect in vivo conditions than 2D cell culture. Based on this, 3D bioprinting technology, which enables to place the desired materials in the desired locations, has been introduced to fabricate tissue models with high structural similarity to the native tissues. Therefore, this review discusses the recent developments in this field and the key features of various types of 3D-bioprinted tissues, particularly those associated with blood vessels or highly vascularized organs, such as the heart, liver, and kidney. Moreover, this review also summarizes the current state of the three categories: (1) chemical substance treatment, (2) 3D bioprinting of lesions, and (3) recapitulation of tumor microenvironments (TME) of 3D bioprinting-based disease models according to their disease modeling approach. Finally, we propose the future directions of 3D bioprinting approaches for the creation of more advanced in vitro biomimetic 3D tissues, as well as the translation of 3D bioprinted tissue models to clinical applications.

  View details for DOI 10.3389/fbioe.2021.685507

  View details for PubMedID 34136473

  View details for PubMedCentralID PMC8201787

• 3D Pancreatic Tissue Modeling <i>in vitro</i>: Advances and Prospects BIOCHIP JOURNAL Kim, M., Hwang, D., Jang, J. 2020; 14 (1): 84-99

  View details for DOI 10.1007/s13206-020-4108-4

  View details for Web of Science ID 000521146800001

• Pancreatic Tissue-Derived Extracellular Matrix Bioink for Printing 3D Cell-Laden Pancreatic Tissue Constructs. Journal of visualized experiments : JoVE Kim, J., Kim, M., Hwang, D. G., Shim, I. K., Kim, S. C., Jang, J. 2019

  Abstract

  The transplantation of pancreatic islets is a promising treatment for patients who suffer from type 1 diabetes accompanied by hypoglycemia and secondary complications. However, islet transplantation still has several limitations such as the low viability of transplanted islets due to poor islet engraftment and hostile environments. In addition, the insulin-producing cells differentiated from human pluripotent stem cells have limited ability to secrete sufficient hormones that can regulate the blood glucose level; therefore, improving the maturation by culturing cells with proper microenvironmental cues is strongly required. In this article, we elucidate protocols for preparing a pancreatic tissue-derived decellularized extracellular matrix (pdECM) bioink to provide a beneficial microenvironment that can increase glucose sensitivity of pancreatic islets, followed by describing the processes for generating 3D pancreatic tissue constructs using a microextrusion-based bioprinting technique.

  View details for DOI 10.3791/60434

  View details for PubMedID 31885383

• 3D cell printing of islet-laden pancreatic tissue-derived extracellular matrix bioink constructs for enhancing pancreatic functions. Journal of materials chemistry. B Kim, J., Shim, I. K., Hwang, D. G., Lee, Y. N., Kim, M., Kim, H., Kim, S. W., Lee, S., Kim, S. C., Cho, D. W., Jang, J. 2019; 7 (10): 1773-1781

  Abstract

  Type 1 diabetes mellitus (T1DM) is a form of diabetes that inhibits or halts insulin production in the pancreas. Although various therapeutic options are applied in clinical settings, not all patients are treatable with such methods due to the instability of the T1DM or the unawareness of hypoglycemia. Islet transplantation using a tissue engineering-based approach may mark a clinical significance, but finding ways to increase the function of islets in 3D constructs is a major challenge. In this study, we suggest pancreatic tissue-derived extracellular matrix as a potential candidate to recapitulate the native microenvironment in transplantable 3D pancreatic tissues. Notably, insulin secretion and the maturation of insulin-producing cells derived from human pluripotent stem cells were highly up-regulated when cultured in pdECM bioink. In addition, co-culture with human umbilical vein-derived endothelial cells decreased the central necrosis of islets under 3D culture conditions. Through the convergence of 3D cell printing technology, we validated the possibility of fabricating 3D constructs of a therapeutically applicable transplant size that can potentially be an allogeneic source of islets, such as patient-induced pluripotent stem cell-derived insulin-producing cells.

  View details for DOI 10.1039/c8tb02787k

  View details for PubMedID 32254919