Publications by authors named "Gwang-Bum Im"

8 Publications

  • Page 1 of 1

Delivery of a spheroids-incorporated human dermal fibroblast sheet increases angiogenesis and M2 polarization for wound healing.

Biomaterials 2021 Aug 7;275:120954. Epub 2021 Jun 7.

School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi, 16419, Republic of Korea. Electronic address:

Low cell engraftment is a major problem in tissue engineering. Although various methods related with cell sheets have been attempted to resolve the issue, low cell viability due to oxygen and nutrient depletion remains an obstacle toward advanced therapeutic applications. Cell therapy using fibroblasts is thought of as a good alternative due to the short doubling times of fibroblasts together with their immunomodulatory properties. Furthermore, three-dimensional (3D) fibroblasts exhibit unique angiogenic and inflammation-manipulating properties that are not present in two-dimensional (2D) forms. However, the therapeutic effect of 3D fibroblasts in tissue regeneration has not been fully elucidated. Macrophage polarization has been widely studied, as it stimulates the transition from the inflammation to the proliferation phase of wound healing. Although numerous strategies have been developed to achieve better polarization of macrophages, the low efficacy of these strategies and safety issues remain problematic. To this end, we introduced a biocompatible flat patch with specifically designed holes that form a spheroids-incorporated human dermal fibroblast sheet (SIS) to mediate the activity of inflammatory cytokines for M2 polarization and increase angiogenic efficacy. We further confirmed in vivo enhancement of wound healing with an SIS-laden skin patch (SISS) compared to conventional cell therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2021.120954DOI Listing
August 2021

Dual Ion Releasing Nanoparticles for Modulating Osteogenic Cellular Microenvironment of Human Mesenchymal Stem Cells.

Materials (Basel) 2021 Jan 15;14(2). Epub 2021 Jan 15.

School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea.

In this study we developed a dual therapeutic metal ion-releasing nanoparticle for advanced osteogenic differentiation of stem cells. In order to enhance the osteogenic differentiation of human mesenchymal stem cells (hMSCs) and induce angiogenesis, zinc (Zn) and iron (Fe) were synthesized together into a nanoparticle with a pH-sensitive degradation property. Zn and Fe were loaded within the nanoparticles to promote early osteogenic gene expression and to induce angiogenic paracrine factor secretion for hMSCs. In vitro studies revealed that treating an optimized concentration of our zinc-based iron oxide nanoparticles to hMSCs delivered Zn and Fe ion in a controlled release manner and supported osteogenic gene expression (RUNX2 and alkaline phosphatase) with improved vascular endothelial growth factor secretion. Simultaneous intracellular release of Zn and Fe ions through the endocytosis of the nanoparticles further modulated the mild reactive oxygen species generation level in hMSCs without cytotoxicity and thus improved the osteogenic capacity of the stem cells. Current results suggest that our dual ion releasing nanoparticles might provide a promising platform for future biomedical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ma14020412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830414PMC
January 2021

Regulation of intracellular transition metal ion level with a pH-sensitive inorganic nanocluster to improve therapeutic angiogenesis by enriching conditioned medium retrieved from human adipose derived stem cells.

Nano Converg 2020 Oct 16;7(1):34. Epub 2020 Oct 16.

School of Chemical Engineering, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.

Cell therapy based on human adipose derived stem cells (hADSCs) is a known potential therapeutic approach to induce angiogenesis in ischemic diseases. However, the therapeutic efficacy of direct hADSC injection is limited by a low cell viability and poor cell engraftment after administration. To improve the outcomes of this kind of approach, various types of nanoparticles have been utilized to improve the therapeutic efficacy of hADSC transplantation. Despite their advantages, the adverse effects of nanoparticles, such as genetic damage and potential oncogenesis based on non-degradable property of nanoparticles prohibit the application of nanoparticles toward the clinical applications. Herein, we designed a transition metal based inorganic nanocluster able of pH-selective degradation (ps-TNC), with the aim of enhancing an hADSC based treatment of mouse hindlimb ischemia. Our ps-TNC was designed to undergo degradation at low pH conditions, thus releasing metal ions only after endocytosis, in the endosome. To eliminate the limitations of both conventional hADSC injection and non-degradable property of nanoparticles, we have collected conditioned medium (CM) from the ps-TNC treated hADSCs and administrated it to the ischemic lesions. We found that intracellular increment of transition metal ion upregulated the hypoxia-inducible factor 1α, which can induce vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expressions. Based on the molecular mechanism, the secretion of VEGF and bFGF by ps-TNC treated hADSCs showed a significant improvement compared to that of untreated cells. Injecting the CM collected from ps-TNC treated hADSCs into the mouse hindlimb ischemia model (ps-TNC-CM group) showed significantly improved angiogenesis in the lesions, with improved limb salvage and decreased muscle degeneration compared to the group injected with CM collected from normal hADSCs (CM group). This study suggests a novel strategy, combining a known angiogenesis molecular mechanism with both an improvement on conventional stem cell therapy and the circumvention of some limitations still present in modern approaches based on nanoparticles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40580-020-00244-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567771PMC
October 2020

NIR-vis-Induced pH-Sensitive TiO Immobilized Carbon Dot for Controllable Membrane-Nuclei Targeting and Photothermal Therapy of Cancer Cells.

ACS Appl Mater Interfaces 2020 Aug 12;12(34):37929-37942. Epub 2020 Aug 12.

Department of Green Bio Engineering, Korea National University of Transportation, Chungju 380-702, Republic of Korea.

This study investigated a selective and sensitive theragnosis system for the specific targeting of the membrane and nuclei based on visible-light and pH-responsive TiO-integrated cross-linked carbon dot (C-CD/TiO) for tumor detection and controllable photothermal therapy. The cross-linking system was formed by boronate ester linkages between the TiO-immobilized Dopa-decyl (D-CD) and zwitterionic-formed CD (Z-CD) for nuclear targeting, which showed fluorescence "off" at physiological pH. The fluorescence recovered to the "on" state in acidic cancer cells owing to cleavages of the boronate ester bonds, resulting in the disruption of the Förster resonance energy transfer that generated different CDs useful for tumor-selective biosensors and therapy. D-CD, which is hydrophobic, can penetrate the hydrophobic sites of the cell membrane; it caused a loss in the hydrophobicity of these sites after visible-light irradiation. This was achieved by the photocatalytic activity of the TiO modulating energy bandgap, whereas the Z-CD targeted the nucleus, as confirmed by merged confocal microscopy images. D-CD augmented by photothermal heat also exhibited selective anticancer activity in the acidic tumor condition but showed only minimal effects at a normal site at pH 7.4. After C-CD/TiO injection to an tumor model, C-CD/TiO efficiently ablated tumors under NIR light irradiation. The C-CD/TiO group showed up-regulation of the pro-apoptotic markers such as and in tumor. This material exhibited its potential as a theragnostic sensor with excellent biocompatibility, high sensitivity, selective imaging, and direct anticancer activity via photothermal therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c11979DOI Listing
August 2020

Bio-application of Inorganic Nanomaterials in Tissue Engineering.

Adv Exp Med Biol 2020 ;1249:115-130

School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi, Republic of Korea.

Inorganic nanomaterials or nanoparticles (INPs) have drawn high attention for their usage in the biomedical field. In addition to the facile synthetic and modifiable property of INPs, INPs have various unique properties that originate from the components of the INPs, such as metal ions that are essential for the human body. Apart from their roles as components of the human body, inorganic materials have unique properties, such as magnetic, antibacterial, and piezoelectric, so that INPs have been widely used as either carriers or inducers. However, most of the bio-applicable INPs, especially those consisting of metal, can cause cytotoxicity. Therefore, INPs require modification to alleviate the harmful effect toward the cells by controlling the release of metal ions from INPs. Even though many attempts have been made to modify INPs, many things, including the side effects of INPs, still remain as obstacles in the bio-application, which need to be elucidated. In this chapter, we introduce novel INPs in terms of their synthetic method and bio-application in tissue engineering.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-981-15-3258-0_8DOI Listing
December 2020

Endosome-triggered ion-releasing nanoparticles as therapeutics to enhance the angiogenic efficacy of human mesenchymal stem cells.

J Control Release 2020 08 23;324:586-597. Epub 2020 May 23.

School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address:

Here, we report that Fe ions delivered into human mesenchymal stem cells (hMSCs) by bioreducible metal nanoparticles (NPs) enhance their angiogenic and cell-homing efficacy by controlling ion-triggered intracellular reactive oxygen species (ROS) and improve cell migration, while reducing cytotoxicity. Endosome-triggered iron-ion-releasing nanoparticles (ETIN) were designed to be low-pH responsive to take advantage of the low-pH conditions (4-5) of endosomes for in situ iron-ion release. Due to the different redox potentials of Fe and Au, only Fe could be ionized and released from our novel ETIN, while Au remained intact after ETIN endocytosis. Treatment with an optimal amount of ETIN led to a mild increase in intracellular ROS levels in hMSCs, which enhanced the expression of HIF-1α, a key trigger for angiogenic growth factor secretion from hMSCs. Treatmetn of hMSCs with ETIN significantly enhanced the expression of angiogenesis- and lesion-targeting-related genes and proteins. Transplantation of ETIN-treated hMSCs significantly enhanced angiogenesis and tissue regeneration in a wound-closing mouse model compared with those in untreated mice and mice that underwent conventional hMSC transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jconrel.2020.05.038DOI Listing
August 2020

Enhancing the Wound Healing Effect of Conditioned Medium Collected from Mesenchymal Stem Cells with High Passage Number Using Bioreducible Nanoparticles.

Int J Mol Sci 2019 Sep 28;20(19). Epub 2019 Sep 28.

School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea.

Injecting human mesenchymal stem cells (hMSCs) at wound sites is known to have a therapeutic effect; however, hMSCs have several limitations, such as low viability and poor engraftment after injection, as well as a potential risk of oncogenesis. The use of a conditioned medium (CM) was suggested as an alternative method for treating various wounds instead of direct hMSC administration. In addition to not having the adverse effects associated with hMSCs, a CM can be easily mass produced and can be stored for long-term, thereby making it useful for clinical applications. In general, a CM is collected from hMSCs with low passage number; whereas, the hMSCs with high passage number are usually discarded because of their low therapeutic efficacy as a result of reduced angiogenic factor secretion. Herein, we used a CM collected from high passage number (passage 12, P12) hMSCs treated with gold-iron nanoparticles (AuFe NPs). Our AuFe NPs were designed to release the iron ion intracellularly via endocytosis. Endosomes with low pH can dissolve iron from AuFe NPs, and thus, the intracellularly released iron ions up-regulate the hypoxia-inducible factor 1α and vascular endothelial growth factor (VEGF) expression. Through this mechanism, AuFe NPs improve the amount of VEGF expression from P12 hMSCs so that it is comparable to the amount of VEGF expression from low passage number (passage 6, P6), without treatment. Furthermore, we injected the CM retrieved from P12 MSCs treated with AuFe NPs in the mouse skin wound model (AuFe P12 group). AuFe P12 group revealed significantly enhanced angiogenesis in the mouse skin wound model compared to the high passage hMSC CM-injected group. Moreover, the result from the AuFe P12 group was similar to that of the low passage hMSC CM-injected group. Both the AuFe P12 group and low passage hMSC CM-injected group presented significantly enhanced re-epithelization, angiogenesis, and tissue remodeling compared to the high passage hMSC CM-injected group. This study reveals a new strategy for tissue regeneration based on CM injection without considering the high cell passage count.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20194835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801963PMC
September 2019

A Disposable Photovoltaic Patch Controlling Cellular Microenvironment for Wound Healing.

Int J Mol Sci 2018 Oct 4;19(10). Epub 2018 Oct 4.

Department of BioNano Technology, Gachon University, Seongnam 13120, Korea.

Electrical stimulation (ES) is known to affect the wound healing process by modulating skin cell behaviors. However, the conventional clinical devices that can generate ES for promoting wound healing require patient hospitalization due to large-scale of the extracorporeal devices. Herein, we introduce a disposable photovoltaic patch that can be applied to skin wound sites to control cellular microenvironment for promoting wound healing by generating ES. In vitro experiment results show that exogenous ES could enhance cell migration, proliferation, expression of extracellular matrix proteins, and myoblast differentiation of fibroblasts which are critical for wound healing. Our disposable photovoltaic patches were attached to the back of skin wound induced mice. Our patch successfully provided ES, generated by photovoltaic energy harvested from the organic solar cell under visible light illumination. In vivo experiment results show that the patch promoted cutaneous wound healing via enhanced host-inductive cell proliferation, cytokine secretion, and protein synthesis which is critical for wound healing process. Unlike the current treatments for wound healing that engage passive healing processes and often are unsuccessful, our wearable photovoltaic patch can stimulate regenerative activities of endogenous cells and actively contribute to the wound healing processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms19103025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213857PMC
October 2018
-->