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      Nano/Micro-Assisted Regenerative Medicine

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      International Journal of Molecular Sciences
      MDPI

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          Abstract

          Regenerative medicine is an emerging discipline aimed at repairing and reestablishing the normal functions of tissues and organs damaged by aging, disease, injury, or congenital disorders. Among the advanced technologies currently under investigation, such as cell therapy, tissue and biomaterial engineering, transplantation, nano/microtechnologies, either alone or in combination with specific cells, such as stem cells, have opened the prospect of nano/micro-assisted regenerative medicine, which has the potential to transform regenerative medicine. This special issue, entitled “Nano/Micro-Assisted Regenerative Medicine” presents two reviews and 11 research articles highlighting recent advances in the use of nano/micro-assisted technologies in regenerative medicine. Kang et al. describe the application of nano and microengineering techniques for the fabrication of native tissue topographies as an alternative to silicone implants, which are known to cause capsular contractures via adverse immune reactions [1]. Bellinghen et al. report that temporomandibular joint regeneration can be improved by nano/micro-assisted functionalization [2]. Yun et al. show that labeling mesenchymal stem cells (MSCs) with superparamagnetic iron oxide nanoparticles (SPIONs) via magnetic retention enhances the homing efficiency of MSCs in olfactory-injured mice [3]. Jeong et al. describe the therapeutic effects of simvastatin-loaded porous microspheres (SIM/PMSs) on inflamed tenocytes in vitro and collagenase-induced Achilles tendinitis in vivo [4]. A new platform of three-dimensional (3D) graphene/arginine-glycine-aspartic acid (RGD) peptide nanoisland composites to enhance the osteogenesis of human adipose-derived MSCs is proposed by Kang et al. [5]. Lee et al. show that acid-degradable poly(ethylene glycol)-poly(amino ketal) (PEG-PAK)-based micelles can be used to improve stromal cell-derived factor-1α (SDF-1α) gene transfection efficacy and angiogenesis of human adipose-derived MSCs for the treatment of ischemic diseases [6]. Kim et al. demonstrate that a reduced graphene oxide-coated biphasic calcium phosphate bone graft material is effective for bone regeneration in rat calvarial defects [7]. Müller et al. demonstrate that amorphous polyphosphate nano/microparticles effectively block the neurotoxic effects of toxic amyloid β-protein fragment 25–35 by rebalancing the β-amyloid-induced decrease in adenosine triphosphate (ATP) levels [8]. Park et al. describe the development of in vitro cancer microtissue arrays on a fibroblast-layered nanofibrous membrane by inkjet printing and their applications to cancer drug screening and gradual 3D cancer studies [9]. Nagai et al. demonstrate that cilostazol ophthalmic nanodispersions have therapeutic effects on retinal disorders caused by diabetes mellitus in streptozotocin-induced diabetic rats [10]. Tatiparti et al. report the development of the carbonic anhydrase-IX selective nanocarrier, human serum albumin-paclitaxel-acetazolamide (HSA-PTX-ATZ), by copper-free ‘click’ chemistry-based synthesis for tumor hypoxia-targeted drug delivery that can be adapted to several types of cancers [11]. The cytotoxicity of peptide liposome incorporated citron-extract nanoparticles and turmeric extract incorporated oil-in-water nanoemulsions on various cell types is evaluated by Zhang et al. [12] and Yoon et al. [13], respectively. Regenerative medicine is constantly evolving from advances in the development of new nano/micro-based materials, such as particles, fibers, composites, and surfaces. This evolution is bolstered by the multidisciplinary and interdisciplinary efforts of scientists in areas such as biotechnology, biomaterials science, chemistry, physics, stem cell biology, developmental biology, and clinical medicine, as well as other areas. In this special issue, promising applications of nano/micro-assisted regenerative medicine in tissue engineering or cancer treatment are introduced, and strategies for the further development of this field are described. We are confident that progress in nano/microtechnologies will continue to fertilize the emerging field of nano/micro-assisted regenerative medicine and provide a wide range of new and improved therapies for the degenerative disease.

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          The Effect of Reduced Graphene Oxide-Coated Biphasic Calcium Phosphate Bone Graft Material on Osteogenesis

          This study was conducted to evaluate the effect of biphasic calcium phosphate (BCP) coated with reduced graphene oxide (rGO) as bone graft materials on bone regeneration. The rGO-coated BCP bone graft material was fabricatied by mixing rGO and BCP at various concentrations. The surface charge of rGO-coated BCP was measured to be −14.43 mV, which formed a static electrostatic interaction. Cell viabilities were significantly diminished at higher concentrations of ≥100 μg/mL. The calvarial defects of 48 rats were implanted rGO-coated BCPs at a weight ratio of 2:1000 (rGO2), 4:1000 (rGO4), and 10:1000 (rGO10), repectively. BCP was used as a control group. The micro-CT and histological analysis were performed to evaluate new bone formation at 2 and 8 weeks after surgery. The results showed that the new bone volume (mm3) was significantly higher in the experimental groups than in the control group. Histological analysis showed that new bone areas (%) were significantly higher in the rGO2 and rGO10 than in the control, and significantly higher in rGO4 than in the rGO2 and rGO10. Conclusively, the rGO-coated BCP was found to be effective on osteogenesis and the concentration of the composite was an important factor.
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            Temporomandibular Joint Regenerative Medicine

            The temporomandibular joint (TMJ) is an articulation formed between the temporal bone and the mandibular condyle which is commonly affected. These affections are often so painful during fundamental oral activities that patients have lower quality of life. Limitations of therapeutics for severe TMJ diseases have led to increased interest in regenerative strategies combining stem cells, implantable scaffolds and well-targeting bioactive molecules. To succeed in functional and structural regeneration of TMJ is very challenging. Innovative strategies and biomaterials are absolutely crucial because TMJ can be considered as one of the most difficult tissues to regenerate due to its limited healing capacity, its unique histological and structural properties and the necessity for long-term prevention of its ossified or fibrous adhesions. The ideal approach for TMJ regeneration is a unique scaffold functionalized with an osteochondral molecular gradient containing a single stem cell population able to undergo osteogenic and chondrogenic differentiation such as BMSCs, ADSCs or DPSCs. The key for this complex regeneration is the functionalization with active molecules such as IGF-1, TGF-β1 or bFGF. This regeneration can be optimized by nano/micro-assisted functionalization and by spatiotemporal drug delivery systems orchestrating the 3D formation of TMJ tissues.
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              Enhanced Homing Technique of Mesenchymal Stem Cells Using Iron Oxide Nanoparticles by Magnetic Attraction in Olfactory-Injured Mouse Models

              Intranasal delivery of mesenchymal stem cells (MSCs) to the olfactory bulb is a promising approach for treating olfactory injury. Additionally, using the homing phenomenon of MSCs may be clinically applicable for developing therapeutic cell carriers. Herein, using superparamagnetic iron oxide nanoparticles (SPIONs) and a permanent magnet, we demonstrated an enhanced homing effect in an olfactory model. Superparamagnetic iron oxide nanoparticles with rhodamine B (IRBs) had a diameter of 5.22 ± 0.9 nm and ζ-potential of +15.2 ± 0.3 mV. IRB concentration of 15 µg/mL was injected with SPIONs into MSCs, as cell viability significantly decreased when 20 μg/mL was used (p ≤ 0.005) compared to in controls. The cells exhibited magnetic attraction in vitro. SPIONs also stimulated CXCR4 (C-X-C chemokine receptor type 4) expression and CXCR4-SDF-1 (Stromal cell-derived factor 1) signaling in MSCs. After injecting magnetized MSCs, these cells were detected in the damaged olfactory bulb one week after injury on one side, and there was a significant increase compared to when non-magnetized MSCs were injected. Our results suggest that SPIONs-labeled MSCs migrated to injured olfactory tissue through guidance with a permanent magnet, resulting in better homing effects of MSCs in vivo, and that iron oxide nanoparticles can be used for internalization, various biological applications, and regenerative studies.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                26 July 2018
                August 2018
                : 19
                : 8
                : 2187
                Affiliations
                Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Korea; bgchoi@ 123456cha.ac.kr
                Author notes
                [* ]Correspondence: soohong@ 123456cha.ac.kr ; Tel.: +82-31-881-7143
                Article
                ijms-19-02187
                10.3390/ijms19082187
                6121569
                30049973
                b5265d8c-295c-41b5-a495-c4d64f5da294
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 23 July 2018
                : 25 July 2018
                Categories
                Editorial

                Molecular biology
                Molecular biology

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