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Nano/Micro-Assisted Regenerative Medicine 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 42761

Special Issue Editor

Prof. Dr. Soo-Hong Lee

E-Mail Website
Guest Editor
Department of Medical Biotechnology, Dongguk University 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Korea
Interests: functional biomaterials; tissue engineering; cell therapy; nano drug delivery system; stem cells; cellular microenvironment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue "Nano/Micro-Assisted Regenerative Medicine" (https://0-www-mdpi-com.brum.beds.ac.uk/journal/ijms/special_issues/nano_regenerative_medicine).

This Special Issue will focus on recent research developments in regenerative medicine using nanotechnology. We welcome review articles, commentaries, and experimental papers applicable to the Special Issue.

The widespread use of the term regenerative medicine is attributed to William A. Haseltine (founder of Human Genome Sciences). Since then, there have been many research studies related to regenerative medicine. The basic concept of “Nano/Micro-Assisted Regenerative Medicine” is to use engineered nanostructures, alone or in combination with specific cells, such as stem cells, to replace, augment or regenerate human tissues/organs to make them functional. The rise of advanced nanotechnology provided breakthrough in this field, as it opened wide applications in tissue engineering, and imaging areas, addressing various limitations in the field. Thus, concepts and discoveries from the nano/micro- bio research provide exciting opportunities in using cells for regeneration of tissues and organs. The Special Issue will focus on recent advances of stem- and tissue-cell engineering/drug delivery/imaging fields. New nanomaterials, animal models, and clinical trials for various diseases are highly appreciated. In addition, the combination of nano and micro technology for vision restoration, skin and bone regeneration and understanding their clinical outcomes are also welcome.

Prof. Dr. Soo-Hong Lee
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Regenerative medicine
  • Nano/micro technology
  • Stem cells Tissue engineering
  • Bone regeneration
  • Wound healing Skin regeneration
  • Drug delivery
  • Imaging
  • Magnetic nanoparticles Ophthalmology
  • Clinical trials

Related Special Issue

Published Papers (7 papers)

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Research

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15 pages, 5748 KiB  
Article
Enhancing Neurogenesis of Neural Stem Cells Using Homogeneous Nanohole Pattern-Modified Conductive Platform
by Yeon-Woo Cho, Da-Seul Kim, Intan Rosalina Suhito, Dong Keun Han, Taek Lee and Tae-Hyung Kim
Int. J. Mol. Sci. 2020, 21(1), 191; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010191 - 26 Dec 2019
Cited by 16 | Viewed by 4282
Abstract
Biocompatible platforms, wherein cells attach and grow, are important for controlling cytoskeletal dynamics and steering stem cell functions, including differentiation. Among various components, membrane integrins play a key role in focal adhesion of cells (18–20 nm in size) and are, thus, highly sensitive [...] Read more.
Biocompatible platforms, wherein cells attach and grow, are important for controlling cytoskeletal dynamics and steering stem cell functions, including differentiation. Among various components, membrane integrins play a key role in focal adhesion of cells (18–20 nm in size) and are, thus, highly sensitive to the nanotopographical features of underlying substrates. Hence, it is necessary to develop a platform/technique that can provide high flexibility in controlling nanostructure sizes. We report a platform modified with homogeneous nanohole patterns, effective in guiding neurogenesis of mouse neural stem cells (mNSCs). Sizes of nanoholes were easily generated and varied using laser interference lithography (LIL), by changing the incident angles of light interference on substrates. Among three different nanohole patterns fabricated on conductive transparent electrodes, 500 nm-sized nanoholes showed the best performance for cell adhesion and spreading, based on F-actin and lamellipodia/filopodia expression. Enhanced biocompatibility and cell adhesion of these nanohole patterns ultimately resulted in the enhanced neurogenesis of mNSCs, based on the mRNAs expression level of the mNSCs marker and several neuronal markers. Therefore, platforms modified with homogeneous nanohole patterns fabricated by LIL are promising for the precise tuning of nanostructures in tissue culture platforms and useful for controlling various differentiation lineages of stem cells. Full article
(This article belongs to the Special Issue Nano/Micro-Assisted Regenerative Medicine 2.0)
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16 pages, 6945 KiB  
Article
Reduction-Triggered Paclitaxel Release Nano-Hybrid System Based on Core-Crosslinked Polymer Dots with a pH-Responsive Shell-Cleavable Colorimetric Biosensor
by Seul Gi Kim, Benny Ryplida, Pham Thi My Phuong, Hyun Jeong Won, Gibaek Lee, Suk Ho Bhang and Sung Young Park
Int. J. Mol. Sci. 2019, 20(21), 5368; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20215368 - 28 Oct 2019
Cited by 10 | Viewed by 2910
Abstract
Herein, we describe the fabrication and characterization of carbonized disulfide core-crosslinked polymer dots with pH-cleavable colorimetric nanosensors, based on diol dye-conjugated fluorescent polymer dots (L-PD), for reduction-triggered paclitaxel (PTX) release during fluorescence imaging-guided chemotherapy of tumors. L-PD were loaded with PTX (PTX loaded [...] Read more.
Herein, we describe the fabrication and characterization of carbonized disulfide core-crosslinked polymer dots with pH-cleavable colorimetric nanosensors, based on diol dye-conjugated fluorescent polymer dots (L-PD), for reduction-triggered paclitaxel (PTX) release during fluorescence imaging-guided chemotherapy of tumors. L-PD were loaded with PTX (PTX loaded L-PD), via π–π stackings or hydrophobic interactions, for selective theragnosis by enhanced release of PTX after the cleavage of disulfide bonds by high concentration of glutathione (GSH) in a tumor. The nano-hybrid system showed fluorescence quenching behavior with less than 2% of PTX released under physiological conditions. However, in a tumor microenvironment, the fluorescence recovered at an acidic-pH, and PTX (approximately 100% of the drug release) was released efficiently out of the matrix by reduction caused by the GSH level in the tumor cells, which improved the effectiveness of the cancer treatment. Therefore, the colorimetric nanosensor showed promising potential in distinguishing between normal and cancerous tissues depending on the surrounding pH and GSH concentrations so that PTX can be selectively delivered into cancer cells for improved cancer diagnosis and chemotherapy. Full article
(This article belongs to the Special Issue Nano/Micro-Assisted Regenerative Medicine 2.0)
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14 pages, 2329 KiB  
Article
Enhancing the Wound Healing Effect of Conditioned Medium Collected from Mesenchymal Stem Cells with High Passage Number Using Bioreducible Nanoparticles
by Gwang-Bum Im, Yeong Hwan Kim, Yu-Jin Kim, Sung-Won Kim, Euiyoung Jung, Gun-Jae Jeong, Ke Wang, Jinheung Kim, Dong-Ik Kim, Tae-Hyung Kim, Gi-Ra Yi, Taekyung Yu and Suk Ho Bhang
Int. J. Mol. Sci. 2019, 20(19), 4835; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20194835 - 28 Sep 2019
Cited by 17 | Viewed by 5169
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Nano/Micro-Assisted Regenerative Medicine 2.0)
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Review

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44 pages, 13500 KiB  
Review
Stimulus-Responsive Nanomedicines for Disease Diagnosis and Treatment
by Gengqi Liu, Jonathan F. Lovell, Lei Zhang and Yumiao Zhang
Int. J. Mol. Sci. 2020, 21(17), 6380; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176380 - 02 Sep 2020
Cited by 43 | Viewed by 5502
Abstract
Stimulus-responsive drug delivery systems generally aim to release the active pharmaceutical ingredient (API) in response to specific conditions and have recently been explored for disease treatments. These approaches can also be extended to molecular imaging to report on disease diagnosis and management. The [...] Read more.
Stimulus-responsive drug delivery systems generally aim to release the active pharmaceutical ingredient (API) in response to specific conditions and have recently been explored for disease treatments. These approaches can also be extended to molecular imaging to report on disease diagnosis and management. The stimuli used for activation are based on differences between the environment of the diseased or targeted sites, and normal tissues. Endogenous stimuli include pH, redox reactions, enzymatic activity, temperature and others. Exogenous site-specific stimuli include the use of magnetic fields, light, ultrasound and others. These endogenous or exogenous stimuli lead to structural changes or cleavage of the cargo carrier, leading to release of the API. A wide variety of stimulus-responsive systems have been developed—responsive to both a single stimulus or multiple stimuli—and represent a theranostic tool for disease treatment. In this review, stimuli commonly used in the development of theranostic nanoplatforms are enumerated. An emphasis on chemical structure and property relationships is provided, aiming to focus on insights for the design of stimulus-responsive delivery systems. Several examples of theranostic applications of these stimulus-responsive nanomedicines are discussed. Full article
(This article belongs to the Special Issue Nano/Micro-Assisted Regenerative Medicine 2.0)
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21 pages, 3105 KiB  
Review
Emerging Potential of Exosomes in Regenerative Medicine for Temporomandibular Joint Osteoarthritis
by Yeon-Hee Lee, Hee-Kyung Park, Q-Schick Auh, Haram Nah, Jae Seo Lee, Ho-Jin Moon, Dong Nyoung Heo, In San Kim and Il Keun Kwon
Int. J. Mol. Sci. 2020, 21(4), 1541; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041541 - 24 Feb 2020
Cited by 55 | Viewed by 12646
Abstract
Exosomes are nanosized vesicles (30–140 nm) of endocytic origin that play important roles in regenerative medicine. They are derived from cell membranes during endocytic internalization and stabilize in biological fluids such as blood and synovia. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative [...] Read more.
Exosomes are nanosized vesicles (30–140 nm) of endocytic origin that play important roles in regenerative medicine. They are derived from cell membranes during endocytic internalization and stabilize in biological fluids such as blood and synovia. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, which, in addition to chronic pain, is characterized by progressive cartilage breakdown, condylar bone remodeling, and synovitis. However, traditional clinical treatments have limited symptom- and structure-modifying effects to restore damaged cartilage and other TMJ tissues. This is due to the limited self-healing capacity of condylar cartilage. Recently, stem-cell-derived exosomes have been studied as an alternative therapeutic approach to tissue repair and regeneration. It is known that trophic regulation of mesenchymal stem cells (MSCs) has anti-inflammatory and immunomodulatory effects under pathological conditions, and research on MSC-derived exosomes is rapidly accumulating. MSC-derived exosomes mimic the major therapeutic effects of MSCs. They affect the activity of immune effector cells and possess multilineage differentiation potential, including chondrogenic and osteogenic differentiation. Furthermore, exosomes are capable of regenerating cartilage or osseous compartments and restoring injured tissues and can treat dysfunction and pain caused by TMJ OA. In this review, we looked at the uniqueness of TMJ, the pathogenesis of TMJ OA, and the potential role of MSC-derived exosomes for TMJ cartilage and bone regeneration. Full article
(This article belongs to the Special Issue Nano/Micro-Assisted Regenerative Medicine 2.0)
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16 pages, 1200 KiB  
Review
Recent Developments in Nanofiber Fabrication and Modification for Bone Tissue Engineering
by Nopphadol Udomluck, Won-Gun Koh, Dong-Jin Lim and Hansoo Park
Int. J. Mol. Sci. 2020, 21(1), 99; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010099 - 21 Dec 2019
Cited by 68 | Viewed by 5418
Abstract
Bone tissue engineering is an alternative therapeutic intervention to repair or regenerate lost bone. This technique requires three essential components: stem cells that can differentiate into bone cells, growth factors that stimulate cell behavior for bone formation, and scaffolds that mimic the extracellular [...] Read more.
Bone tissue engineering is an alternative therapeutic intervention to repair or regenerate lost bone. This technique requires three essential components: stem cells that can differentiate into bone cells, growth factors that stimulate cell behavior for bone formation, and scaffolds that mimic the extracellular matrix. Among the various kinds of scaffolds, highly porous nanofibrous scaffolds are a potential candidate for supporting cell functions, such as adhesion, delivering growth factors, and forming new tissue. Various fabricating techniques for nanofibrous scaffolds have been investigated, including electrospinning, multi-axial electrospinning, and melt writing electrospinning. Although electrospun fiber fabrication has been possible for a decade, these fibers have gained attention in tissue regeneration owing to the possibility of further modifications of their chemical, biological, and mechanical properties. Recent reports suggest that post-modification after spinning make it possible to modify a nanofiber’s chemical and physical characteristics for regenerating specific target tissues. The objectives of this review are to describe the details of recently developed fabrication and post-modification techniques and discuss the advanced applications and impact of the integrated system of nanofiber-based scaffolds in the field of bone tissue engineering. This review highlights the importance of nanofibrous scaffolds for bone tissue engineering. Full article
(This article belongs to the Special Issue Nano/Micro-Assisted Regenerative Medicine 2.0)
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14 pages, 3322 KiB  
Review
Cell-Electrospinning and Its Application for Tissue Engineering
by Jiyoung Hong, Miji Yeo, Gi Hoon Yang and GeunHyung Kim
Int. J. Mol. Sci. 2019, 20(24), 6208; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20246208 - 09 Dec 2019
Cited by 108 | Viewed by 6260
Abstract
Electrospinning has gained great interest in the field of regenerative medicine, due to its fabrication of a native extracellular matrix-mimicking environment. The micro/nanofibers generated through this process provide cell-friendly surroundings which promote cellular activities. Despite these benefits of electrospinning, a process was introduced [...] Read more.
Electrospinning has gained great interest in the field of regenerative medicine, due to its fabrication of a native extracellular matrix-mimicking environment. The micro/nanofibers generated through this process provide cell-friendly surroundings which promote cellular activities. Despite these benefits of electrospinning, a process was introduced to overcome the limitations of electrospinning. Cell-electrospinning is based on the basic process of electrospinning for producing viable cells encapsulated in the micro/nanofibers. In this review, the process of cell-electrospinning and the materials used in this process will be discussed. This review will also discuss the applications of cell-electrospun structures in tissue engineering. Finally, the advantages, limitations, and future perspectives will be discussed. Full article
(This article belongs to the Special Issue Nano/Micro-Assisted Regenerative Medicine 2.0)
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