Jeonghyun Son

All Publications

• Prevascularized grafts with spatially organized MSC spheroids to accelerate therapeutic angiogenesis in ischemic disease. Angiogenesis Son, J., Naren, A., Mohamed, H. J., Ahn, M., Ha, W., Kim, M. K., Jeon, S., Kim, B. S., Cho, Y. K., Takeuchi, S., Kang, H. W. 2026; 29 (3)

  Abstract

  Ischemic diseases, characterized by impaired blood flow and progressive tissue necrosis, remain a major challenge in regenerative medicine. Surgical revascularization remains the gold standard for restoring blood flow in major vessels, but still shows limited effects on microvascular regeneration. To address this unmet need, various strategies in therapeutic angiogenesis have been explored to induce microvascular formation, including delivery of bioactive molecules, stem cells, or pre-vascularized grafts. However, injection-based approaches often suffer from off-target effects, and conventional implantable grafts lack sufficient angiogenic secretory activity. To address these limitations, we aimed to develop a dual-function prevascularized graft that accelerates neovascularization and promotes vascular integration to restore tissue perfusion in ischemic conditions.The graft was engineered by combining a microvascular pattern (µVP) with spatially organized mesenchymal stem cell (MSC) spheroids, fabricated via high-precision coprinting of endothelial cells and MSCs. Optimization of spheroid density and spatial arrangement enhanced VEGF secretion and increased host capillary infiltration nearly two-fold. In a murine critical limb ischemia model, implantation of these engineered grafts achieved a 60% limb salvage rate and reduced limb loss by ~ 15%, representing a 4.5-fold improvement over conventional grafts. Histological and morphometric analyses confirmed reduced muscle degeneration, enhanced neovascularization, and seamless anastomosis between engineered and host vessels.These findings demonstrate a dual-functional graft that couples paracrine stimulation with structural vascular support, providing a promising regenerative strategy to promote therapeutic angiogenesis and ischemia therapy, while indicating its potential for preclinical and future clinical applications in ischemic disease.

  View details for DOI 10.1007/s10456-026-10059-3

  View details for PubMedID 42265511

  View details for PubMedCentralID PMC13249923

• Triple-Scale Endothelialized Tubular Networks via Hybrid Biofabrication for Scalable Vascular Tissue Engineering. Advanced healthcare materials Son, J., Kim, D., Choi, J., Eom, S., Skylar-Scott, M. A., Kim, D. S., Kang, H. W. 2025: e03334

  Abstract

  The human vascular system is a sophisticated hierarchical network branching from large-diameter vessels to fine capillaries. Recapitulating this hierarchy remains a major biofabrication challenge, as oxygen diffusion from the nearest capillary is limited to ≈200 µm in native tissues, while current vascularized constructs struggle to maintain stable perfusion and functional multiscale architectures. To address this, a hybrid fabrication strategy is introduced that combines top-down microfabrication of tubular scaffolds via electrospinning with bottom-up bioprinting of cell-laden bioinks. This approach enables the engineering of spatially programmable endothelialized tubular networks across three scales: macrovessels (≈3 mm), mesovessels (500-2000 µm), and capillaries (10-25 µm). Electrospun macrovessels exhibit artery-like mechanical properties in longitudinal and circumferential directions. Bioprinting enables precise control over meso- and capillary-scale vessels, facilitating the hierarchical patterning of complex architectures. Integrated triple-scale endothelialized tubular networks formed interconnected, perfusable architectures comprising spatially patterned capillaries and enhanced diffusive transport by more than fivefold. Dynamic culture within endothelialized tubular networks of 5 mm thick tissue constructs supports high cell viability, rapid capillary formation, and in vivo-like endothelial phenotypes under moderate flow. This work uniquely enables scalable vascular-mimetic architectures with artery-like mechanical properties and spatially defined capillaries, representing a previously unattainable integration in angiogenesis, bioprinting, electrospinning, scaled-up tissue constructs, vascular tissue engineeringlarge-scale vascular constructs.

  View details for DOI 10.1002/adhm.202503334

  View details for PubMedID 41361959

• Bioprinting Vascularized Constructs for Clinical Relevance: Engineering Hydrogel Systems for Biological Maturity. Gels (Basel, Switzerland) Son, J., Li, S., Jeong, W. 2025; 11 (8)

  Abstract

  Vascularization remains a critical challenge in tissue engineering, limiting graft survival, integration, and clinical translation. Although bioprinting enables spatial control over vascular architectures, many existing approaches prioritize geometric precision over biological performance. Bioprinted vasculature can be understood as a dynamic and time-dependent system that requires tissue-specific maturation. Within this framework, hydrogel systems act as active microenvironments rather than passive scaffolds. Hydrogel platforms vary from natural matrices and synthetic polymers to bioinspired or stimuli-responsive systems, each offering tunable control over stiffness, degradation, and biochemical signaling needed for vascular maturation. The design requirements of large and small vessels differ in terms of mechanical demands, remodeling capacity, and host integration. A key limitation in current models is the absence of time-resolved evaluation, as critical processes such as lumen formation, pericyte recruitment, and flow-induced remodeling occur progressively and are not captured by static endpoints. Advancements in bioprinting technologies are evaluated based on their capacity to support hydrogel-mediated vascularization across varying length scales and structural complexities. A framework for functional assessment is proposed, and translational challenges related to immunogenicity, scalability, and regulatory requirements are discussed. Such integration of hydrogel-driven biological cues and bioprinting fidelity is critical to advancing vascularized constructs toward clinical translation.

  View details for DOI 10.3390/gels11080636

  View details for PubMedID 40868767

  View details for PubMedCentralID PMC12385750

• Bioprinting of Adipose Tissue Graft with Enhanced Neo-Vessel Formation in Vivo. Advanced healthcare materials Mohamed, H. J., Jeong, W., Son, J., Kang, H. W. 2025: e2500627

  Abstract

  Adipose tissue (AT) grafts are widely used in clinical procedures including soft-tissue augmentation and post-trauma reconstruction. However, the slow vascularization of conventional AT grafts poses a challenge to their in vivo preservation. To address this challenge, an innovative AT graft is engineered using adipose-derived stem cell (ADSC) spheroids to enhance blood vessel infiltration. A polycaprolactone (PCL) framework containing precisely positioned ADSC spheroids is 3D bioprinted, and mechanically dissociated fat tissue is loaded into the framework to produce AT grafts. The spheroid diameter and pattern are optimized to significantly enhance the secretion of angiogenic factors from ADSCs in vivo. During an eight-week in vivo experiment, the bioprinted and transplanted AT grafts demonstrated an impressive 8 fold increase in neo-vessel formation compared to those in conventional grafts. This heightened neovascularization is directly correlated with a substantial improvement in transplanted AT survival and a 70% reduction in fibrous tissue formation. These findings underscore the pivotal role of ADSC spheroid-mediated paracrine signaling in facilitating robust integration with the host vascular system. The novel approach significantly enhanced the long-term viability and preservation of AT grafts by promoting blood vessel infiltration, paving the way for the development of highly vascularized AT grafts for clinical applications.

  View details for DOI 10.1002/adhm.202500627

  View details for PubMedID 40509638

• Clinically Relevant and Precisely Printable Live Adipose Tissue-Based Bio-Ink for Volumetric Soft Tissue Reconstruction. Advanced healthcare materials Jeong, W., Son, J., Choi, J., Han, J., Jeon, S., Kim, M. K., Ha, W., Kang, H. W. 2024: e2402680

  Abstract

  Autologous fat is widely used in soft tissue reconstruction; however, significant volume reduction owing to necrosis and degradation of the transplanted adipose tissue (AT) remains a major challenge. To address this issue, a novel live AT micro-fragment-based bio-ink (ATmf bio-ink) compatible with precision 3D printing, is developed. Live AT micro-fragments of ≈280 µm in size are prepared using a custom tissue micronizer and they are incorporated into a fibrinogen/gelatin mixture to create the ATmf bio-ink. AT micro-fragments exhibit high viability and preserve the heterogeneous cell population and extracellular matrix of the native AT. The developed bio-ink enables precise micropatterning and provides an excellent adipo-inductive microenvironment. AT grafts produced by co-printing the bio-ink with polycaprolactone demonstrate a 500% improvement in volume retention and a 300% increase in blood vessel infiltration in vivo compared with conventional microfat grafts. In vivo engraftment of AT grafts is further enhanced by using a stem cell-laden ATmf bio-ink. Last, it is successfully demonstrated that the bio-ink is enabled for the creation of clinically relevant and patient-specific AT grafts for patients undergoing partial mastectomy. This novel ATmf bio-ink for volumetric soft tissue reconstruction offers a pioneering solution for addressing the limitations of existing clinical techniques.

  View details for DOI 10.1002/adhm.202402680

  View details for PubMedID 39466900

• Bioprinting of pre-vascularized constructs for enhanced <i>in vivo</i> neo-vascularization BIOFABRICATION Son, J., Mohamed, H., Ha, W., Naren, A., Choi, C., Kwon, Y., Park, S., Joung, H., Kang, H. 2023; 15 (3)

  Abstract

  Pre-vascularization has been receiving significant attention for developing implantable engineered 3D tissues. While various pre-vascularization techniques have been developed to improve graft vascularization, the effect of pre-vascularized patterns onin vivoneo-vessel formation has not been studied. In this study, we developed a functional pre-vascularized construct that significantly promotes graft vascularization and conductedin vivoevaluations of the micro-vascular patterns (μVPs) in various printed designs.μVP formation, composed of high-density capillaries, was induced by the co-printing of endothelial cells and adipose-derived stem cells (ADSC). We implanted the printed constructs with variousμVP designs into a murine femoral arteriovenous bundle model and evaluated graft vascularization via 3D visualization and immune-histological analysis of the neo-vessels. TheμVP-distal group (μVP located away from the host vessel) showed approximately two-fold improved neo-vascularization compared to theμVP-proximal group (μVP located near the host vessel). Additionally, we confirmed that theμVP-distal group can generate the angiogenic factor gradient spatial environment for graft vascularization via computational simulations. Based on these results, the ADSC mono pattern (AMP), which secretes four times higher angiogenic factors thanμVP, was added to theμVP + AMP group design. TheμVP + AMP group showed approximately 1.5- and 1.9-fold higher total sprouted neo-vessel volume than theμVP only and AMP only groups, respectively. In immunohistochemical staining analysis, theμVP + AMP group showed two-fold improved density and diameter of the matured neo-vessels. To summarize, these findings demonstrate graft vascularization accelerated due to design optimization of our pre-vascularized constructs. We believe that the developed pre-vascularization printing technique will facilitate new possibilities for the upscaling of implantable engineered tissues/organs.

  View details for DOI 10.1088/1758-5090/acc9de

  View details for Web of Science ID 000976631600001

  View details for PubMedID 37011612

• Development of Muller cell-based 3D biomimetic model using bioprinting technology BIOMEDICAL MATERIALS Jung, S., Son, J., Yi, S., Kim, K., Park, H., Kang, H., Kim, H. 2023; 18 (1)

  Abstract

  Müller cells are the principal glial cells for the maintenance of structural stability and metabolic homeostasis in the human retina. Although variousin vitroexperiments using two-dimensional (2D) monolayer cell cultures have been performed, the results provided only limited results because of the lack of 3D structural environment and different cellular morphology. We studied a Müller cell-based 3D biomimetic model for use in experiments on thein vivo-like functions of Müller cells within the sensory retina. Isolated primary Müller cells were bioprinted and a 3D-aligned architecture was induced, which aligned Müller cell structure in retinal tissue. The stereographic and functional characteristics of the biomimetic model were investigated and compared to those of the conventional 2D cultured group. The results showed the potential to generate Müller cell-based biomimetic models with characteristic morphological features such as endfeet, soma, and microvilli. Especially, the 3D Müller cell model under hyperglycemic conditions showed similar responses as observed in thein vivodiabetic model with retinal changes, whereas the conventional 2D cultured group showed different cytokine and growth factor secretions. These results show that our study is a first step toward providing advanced tools to investigate thein vivofunction of Müller cells and to develop complete 3D models of the vertebrate retina.

  View details for DOI 10.1088/1748-605X/aca0d5

  View details for Web of Science ID 000890540500001

  View details for PubMedID 36343367

• Engineering Tissue-Specific, Multiscale Microvasculature with a Capillary Network for Prevascularized Tissue SMALL METHODS Son, J., Hong, S., Lim, J., Jeong, W., Jeong, J., Kang, H. 2021; 5 (10): e2100632

  Abstract

  Although there are various pre-existing technologies for engineering vasculatures, multiscale modeling of the architecture of human vasculature at a capillary scale remains a challenge. In this study, a novel technology is developed for the production of a functional, multiscale microvasculature comprising of endothelialized channels and tissue-specific capillary networks. Perfusable, endothelialized channels are bioprinted, after which angiogenic sprouts are grown into user-designed capillary networks. The induction of branched and liver-lobule-like capillary networks confirm that the technology can produce various types of tissue-specific multiscale microvasculatures. Further, the channels and capillaries are deemed to be functional when evaluated in vitro. An ex vivo assay demonstrates that the microvasculature can induce neovessel ingrowth, integrate with host vessels, and facilitate blood flow. Remarkably, blood flows through the implanted capillary network without any change in its morphology. Finally, the technology is applied to produce a vascularized liver tissue; it significantly improves its hepatic function. It is believed that this new technology will create new possibilities in the development of highly vascularized and functional tissues/organs on a clinically relevant scale.

  View details for DOI 10.1002/smtd.202100632

  View details for Web of Science ID 000685444100001

  View details for PubMedID 34927948

• In Vitro Mechanical and Biological Properties of 3D Printed Polymer Composite and β-Tricalcium Phosphate Scaffold on Human Dental Pulp Stem Cells MATERIALS Cao, S., Han, J., Sharma, N., Msallem, B., Jeong, W., Son, J., Kunz, C., Kang, H., Thieringer, F. M. 2020; 13 (14)

  Abstract

  3D printed biomaterials have been extensively investigated and developed in the field of bone regeneration related to clinical issues. However, specific applications of 3D printed biomaterials in different dental areas have seldom been reported. In this study, we aimed to and successfully fabricated 3D poly (lactic-co-glycolic acid)/β-tricalcium phosphate (3D-PLGA/TCP) and 3D β-tricalcium phosphate (3D-TCP) scaffolds using two relatively distinct 3D printing (3DP) technologies. Conjunctively, we compared and investigated mechanical and biological responses on human dental pulp stem cells (hDPSCs). Physicochemical properties of the scaffolds, including pore structure, chemical elements, and compression modulus, were characterized. hDPSCs were cultured on scaffolds for subsequent investigations of biocompatibility and osteoconductivity. Our findings indicate that 3D printed PLGA/TCP and β-tricalcium phosphate (β-TCP) scaffolds possessed a highly interconnected and porous structure. 3D-TCP scaffolds exhibited better compressive strength than 3D-PLGA/TCP scaffolds, while the 3D-PLGA/TCP scaffolds revealed a flexible mechanical performance. The introduction of 3D structure and β-TCP components increased the adhesion and proliferation of hDPSCs and promoted osteogenic differentiation. In conclusion, 3D-PLGA/TCP and 3D-TCP scaffolds, with the incorporation of hDPSCs as a personalized restoration approach, has a prospective potential to repair minor and critical bone defects in oral and maxillofacial surgery, respectively.

  View details for DOI 10.3390/ma13143057

  View details for Web of Science ID 000554119200001

  View details for PubMedID 32650530

  View details for PubMedCentralID PMC7412522

• Flexibility Enhancement of Poly(lactide-<i>co</i>-glycolide) for Fused Deposition Modeling Technology INTERNATIONAL JOURNAL OF PRECISION ENGINEERING AND MANUFACTURING-GREEN TECHNOLOGY Jeon, S., Han, J., Jeong, W., Son, J., Kim, J., Kang, H. 2019; 6 (3): 465-475

  View details for DOI 10.1007/s40684-019-00067-8

  View details for Web of Science ID 000474397800004