Biology subjects

Jeon, O.

Publications and source records attributed to Jeon, O..

10 recordsLinked to original sources

bioRxiv2025

A 4D Bio-Kirigami Strategy for Engineering Complex Tissue Curvatures

AbstractFour-dimensional (4D) systems offer a promising approach for generating sophisticated dynamic structures that mimic native tissue architectures. Among those, Kirigami strategies enable precise, localized control over morphing behaviors, yet their application in 4D tissue engineering remains unexplored. Here, we present a bio-Kirigami system that facilitates the creation of dynamic, transformable structures through spatially patterned hydrogels with distinct deformation modes dictated by encoded swelling differentials. The system consists of two biomaterial components: (1) a photocrosslinked hydrogel framework with controlled degradation and swelling behavior that drives the shape transformation and (2) a rigid support hydrogel frame. By leveraging photolithographic patterning, complex structures with continuously evolving configurations were achieved through preprogrammed deformations. Bio- Kirigami hydrogels encapsulating stem cells developed into tissue-like constructs with sophisticated configurations when cultured in tissue-specific environment. Notably, the engineered tissue constructs kept their shape integrity after excision from the outer support, demonstrating a robust platform for achieving intricate tissue curvatures.

bioengineering↗

bioRxiv2025

Photocrosslinkable and biodegradable hydrogels for the controlled delivery of exosomes

Local and controlled delivery of exosomes using hydrogels can improve the efficacy of exosome-based therapeutics. Hydrogels based on oxidized and methacrylated alginate (OMA) can be produced through photocrosslinking and exhibit controllable degradability. The degradation properties of OMA hydrogels can be tailored by varying the alginate oxidation degree, which is advantageous for exploring new therapeutic strategies. Here, we prepared photocrosslinkable, biodegradable, cytocompatible, and tunable alginate hydrogels for exosome delivery. We synthesized OMA with different degrees of alginate oxidation to generate OMA hydrogels that undergo both rapid and slow degradation. The degradation rate, swelling ratio and mechanical stability of the OMA hydrogels were investigated. Likewise, we examined exosome release rate and kinetics. The cytocompatibility and functionality of these systems were confirmed. Increasing the alginate oxidation degree greatly enhanced the degradation of OMA hydrogels. Rapid degradation correlated with accelerated exosome release, while slow degradation correlated with enhanced exosome retention. Physicochemical properties including the rheological behavior and swelling also influenced the exosome release rate. Kinetic equation fits showed that the Korsmeyer-Peppas model can be used to describe the release process. These findings demonstrate that OMA hydrogels are suitable delivery carriers for the controlled release of exosomes and highlight the potential use of this technology in applications that depend on either rapid or slow exosome delivery and the temporary presence of the hydrogel, including tissue engineering, wound healing and localized and targeted drug delivery.

bioengineering↗

bioRxiv2025

In situ cell-only bioprinting of patterned prevascular tissue into bioprinted high-density stem cell-laden microgel bioinks for vascularized bone tissue regeneration

Recently, microgels have been widely used in three-dimensional (3D) bioprinting as both supporting baths and bioinks. As a bioink, microgels have several unique properties, such as shear-thinning and self-healing behaviors with tunable mechanics, making them useful in 3D bioprinting. While cell encapsulated microgels offer many advantages in 3D bioprinting, they also have some limitations. It is still challenging to produce large quantities of cell encapsulated microgels with consistent quality and properties due to processes that are often complex and time-consuming. In this study, stem cell encapsulated, photocrosslinkable, shear-thinning and self-healing alginate microgel (SSAM) bioinks have been successfully fabricated via simple mixing of an oxidized and methacrylated alginate solution with suspended stem cells and a supersaturated calcium sulfate slurry solution through a custom-made spiral mixing unit. The SSAM bioinks can be bioprinted into complex 3D structures with both high resolution and shape fidelity due to their shear-thinning and self-healing properties. The 3D bioprinted SSAM bioinks can then serve as a supporting bath for the creation of prevascular network patterns using an individual cell-only prevasculogenic bioink within the 3D printed constructs. The prevascular network patterned 3D bioprinted constructs can be further stabilized by secondary photocrosslinking of the SSAMs, which enables long-term culture of the printed constructs for functional vascularized osteogenic tissue formation by differentiation of the bioprinted cells. The SSAM bioinks and individual cell-only printing technique enable in situ bioprinting of prevascularized tissue constructs in a mouse calvarial bone defect, achieving mechanical stability and ensuring the in situ bioprinted constructs remain within the defect.

bioengineering↗

bioRxiv2024

Biofabrication of engineered tissues by 3D bioprinting of tissue specific high cell-density bioinks

Bioprinting of high cell-density bioinks is a promising technique for cellular condensation-based tissue engineering and regeneration medicine. However, it remains difficult to create precisely controlled complex structures and organization of tissues with high cell-density bioink-based bioprinting for tissue specific condensation. In this study, we present newly biofabricated tissues from directly assembled, tissue specific, high cell-density bioinks which have been three-dimensionally printed into a photocrosslinkable and biodegradable hydrogel microparticle supporting bath. Three types of tissue specific high cell-density bioinks have been prepared with individual stem cells or stem cell aggregates by incorporation of growth factor-loaded gelatin microparticles. The bioprinted tissue specific high cell-density bioinks in the photocrosslinked microgel supporting bath condense together and differentiate down tissue-specific lineages to form multi-phase tissues (e.g., osteochondral tissues). By changing the growth factors and cell types, these tissue specific high cell-density bioinks enable engineering of various functional tissues with controlled architecture and organization of cells.

bioengineering↗

bioRxiv2024

In situ cell condensation-based cartilage tissue engineering via immediately implantable high-density stem cell core and rapidly degradable shell microgels

Formation of chondromimetic human mesenchymal stem cells (hMSCs) condensations typically required in vitro culture in defined environments. In addition, extended in vitro culture in differentiation media over several weeks is usually necessary prior to implantation, which is costly, time consuming and delays clinical treatment. Here, this study reports on immediately implantable core/shell microgels with a high-density hMSC-laden core and rapidly degradable hydrogel shell. The hMSCs in the core formed cell condensates within 12 hours and the oxidized and methacrylated alginate (OMA) hydrogel shells were completely degraded within 3 days, enabling spontaneous and precipitous fusion of adjacent condensed aggregates. By delivering transforming growth factor-{beta}1 (TGF-{beta}1) within the core, the fused condensates were chondrogenically differentiated and formed cartilage microtissues. Importantly, these hMSC-laden core/shell microgels, fabricated without any in vitro culture, were subcutaneously implanted into mice and shown to form cartilage tissue via cellular condensations in the core after 3 weeks. This innovative approach to form cell condensations in situ without in vitro culture that can fuse together with each other and with host tissue and be matured into new tissue with incorporated bioactive signals, allows for immediate implantation and may be a platform strategy for cartilage regeneration and other tissue engineering applications.

bioengineering↗

bioRxiv2022

Optimizing bioink composition for human chondrocyte expression of lubricin

The surface zone of articular cartilage is the first area impacted by cartilage defects, commonly resulting in osteoarthritis. Chondrocytes in the surface zone of articular cartilage synthesize and secrete lubricin, a proteoglycan that functions as a lubricant protecting the deeper layers from shear stress. 3D bioprinting is a tissue engineering technique that uses cells encapsulated in biomaterials to fabricate 3D constructs. Gelatin methacrylate (GelMA) is a frequently used biomaterial for 3D bioprinting cartilage. Oxidized methacrylated alginate (OMA) is a chemically modified alginate designed for its tunable degradation rate and mechanical properties. To determine an optimal combination of GelMA and OMA for lubricin expression, we used our novel high-throughput human articular chondrocyte reporter system. Primary human chondrocytes were transduced with PRG4 (lubricin) promoter-driven Gaussia luciferase, allowing for temporal assessment of lubricin expression. A lubricin expression driven Design of Experiment screen and subsequent validation identified 14% GelMA/2% OMA for further study. Therefore, 14% GelMA/2% OMA, 14% GelMA and 16% GelMA were 3D bioprinted. The combination of lubricin protein expression and shape retention over the 22 days in culture, determined the 14% GelMA/2%OMA to be the optimal formulation for lubricin secretion.

bioengineering↗

bioRxiv2022

Long-term functional regeneration of radiation damaged salivary glands through delivery of a neurogenic hydrogel

Salivary gland acinar cells are severely depleted after radiotherapy for head and neck cancer, leading to loss of saliva and extensive oro-digestive complications. With no regenerative therapies available, organ dysfunction is irreversible. Here using the adult murine system, we demonstrate radiation-damaged salivary glands can be functionally regenerated via sustained delivery of the neurogenic muscarinic receptor agonist, cevimeline. We show that endogenous gland repair coincides with increased nerve activity and acinar cell division that is limited to the first week post-radiation, with extensive acinar cell degeneration, dysfunction and cholinergic denervation occurring thereafter. However, we discovered that mimicking cholinergic muscarinic input via sustained local delivery of a cevimeline-alginate hydrogel was sufficient to regenerate innervated acini and retain physiological saliva secretion at non-irradiated levels over the long-term (> 3 months). Thus, we reveal a novel regenerative approach for restoring epithelial organ structure and function that has significant implications for human patients. TeaserNovel application of an injectable neurogenic-based hydrogel for restoring the structure and function of radiation-damaged tissue.

cell biology↗

bioRxiv2021

Stem cell-laden hydrogel bioink for generation of high resolution and fidelity engineered tissues with complex geometries

Recently, 3D bioprinting has been explored as a promising technology for biomedical applications with the potential to create complex structures with precise features. Cell encapsulated hydrogels composed of materials such as gelatin, collagen, hyaluronic acid, alginate and polyethylene glycol have been widely used as bioinks for 3D bioprinting. However, since most hydrogel-based bioinks may not allow rapid stabilization immediately after 3D bioprinting, achieving high resolution and fidelity to the intended architecture is a common challenge in 3D bioprinting of hydrogels. In this study, we have utilized shear-thinning and self-healing ionically crosslinked oxidized and methacrylated alginates (OMAs) as a bioink, which can be rapidly gelled by its self-healing property after bioprinting and further stabilized via secondary crosslinking. It was successfully demonstrated that stem cell-laden calcium-crosslinked OMA hydrogels can be bioprinted into complicated 3D tissue structures with both high resolution and fidelity. Additional photocrosslinking enables long-term culture of 3D bioprinted constructs for formation of functional tissue by differentiation of encapsulated human mesenchymal stem cells.

bioengineering↗

bioRxiv2019

Living cell-only bioink and photocurable supporting medium for printing and generation of engineered tissues with complex geometries

Scaffold-free engineering of three-dimensional (3D) tissue has focused on building sophisticated structures to achieve functional constructs. Although the development of advanced manufacturing techniques such as 3D printing has brought remarkable capabilities to the field of tissue engineering, technology to create and culture individual cell only-based high-resolution tissues, without an intervening biomaterial scaffold to maintain construct shape and architecture, has been unachievable to date. In this report, we introduce a cell printing platform which addresses the aforementioned challenge and permits 3D printing and long-term culture of a living cell-only bioink lacking a biomaterial carrier for functional tissue formation. A biodegradable and photocrosslinkable microgel supporting bath serves initially as a fluid, allowing free movement of the printing nozzle for high-resolution cell extrusion, while also presenting solid-like properties to sustain the structure of the printed constructs. The printed human stem cells, which are the only component of the bioink, couple together via transmembrane adhesion proteins and differentiate down tissue-specific lineages while being cultured in a further photocrosslinked supporting bath to form bone and cartilage tissue with precisely controlled structure. Collectively, this system, which is applicable to general 3D printing strategies, is paradigm shifting for printing of scaffold-free individual cells, cellular condensations and organoids, and may have far reaching impact in the fields of regenerative medicine, drug screening, and developmental biology.

bioengineering↗

bioRxiv2019

A Proteomic Atlas of Senescence-Associated Secretomes for Aging Biomarker Development

The senescence-associated secretory phenotype (SASP) has recently emerged as a driver of, and promising therapeutic target for, multiple age-related conditions, ranging from neurodegeneration to cancer. The complexity of the SASP, typically assessed by a few dozen secreted proteins, has been greatly underestimated, and a small set of factors cannot explain the diverse phenotypes it produces in vivo. Here, we present the SASP Atlas, a comprehensive proteomic database of soluble and exosome SASP factors originating from multiple senescence inducers and cell types. Each profile consists of hundreds of largely distinct proteins, but also includes a subset of proteins elevated in all SASPs. Our analyses identify several candidate biomarkers of cellular senescence that overlap with aging markers in human plasma, including GDF15, STC1 and SERPINs, which significantly correlated with age in plasma from a human cohort, the Baltimore Longitudinal Study of Aging. Our findings will facilitate the identification of proteins characteristic of senescence-associated phenotypes and catalog potential senescence biomarkers to assess the burden, originating stimulus and tissue of origin of senescent cells in vivo.\n\nAbbreviationsATV, atazanavir treatment; BLSA, Baltimore Longitudinal Study of Aging; CTL, control; DDA, data-dependent acquisition; DAMP, damage-associated molecular pattern; DIA, data-independent acquisition; eSASP, extracellular vesicle senescence associated secretory phenotype; EVs, extracellular vesicles; IR, X-irradiation; MS, mass spectrometry; RAS, inducible RAS overexpression; SA-{beta}-Gal, senescence-associated {beta}-galactosidase; SEN, senescent; sSASP, soluble senescence associated secretory phenotype.

cell biology↗