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1.
Sensors (Basel) ; 23(4)2023 Feb 17.
Article in English | MEDLINE | ID: mdl-36850876

ABSTRACT

With the development of wearable devices such as smartwatches, several studies have been conducted on the recognition of various human activities. Various types of data are used, e.g., acceleration data collected using an inertial measurement unit sensor. Most scholars segmented the entire timeseries data with a fixed window size before performing recognition. However, this approach has limitations in performance because the execution time of the human activity is usually unknown. Therefore, there have been many attempts to solve this problem through the method of activity recognition by sliding the classification window along the time axis. In this study, we propose a method for classifying all frames rather than a window-based recognition method. For implementation, features extracted using multiple convolutional neural networks with different kernel sizes were fused and used. In addition, similar to the convolutional block attention module, an attention layer to each channel and spatial level is applied to improve the model recognition performance. To verify the performance of the proposed model and prove the effectiveness of the proposed method on human activity recognition, evaluation experiments were performed. For comparison, models using various basic deep learning modules and models, in which all frames were classified for recognizing a specific wave in electrocardiography data were applied. As a result, the proposed model reported the best F1-score (over 0.9) for all kinds of target activities compared to other deep learning-based recognition models. Further, for the improvement verification of the proposed CEF method, the proposed method was compared with three types of SW method. As a result, the proposed method reported the 0.154 higher F1-score than SW. In the case of the designed model, the F1-score was higher as much as 0.184.


Subject(s)
Deep Learning , Humans , Semantics , Acceleration , Human Activities , Attention
2.
Sensors (Basel) ; 22(9)2022 Apr 20.
Article in English | MEDLINE | ID: mdl-35590844

ABSTRACT

Skeleton data, which is often used in the HCI field, is a data structure that can efficiently express human poses and gestures because it consists of 3D positions of joints. The advancement of RGB-D sensors, such as Kinect sensors, enabled the easy capture of skeleton data from depth or RGB images. However, when tracking a target with a single sensor, there is an occlusion problem causing the quality of invisible joints to be randomly degraded. As a result, multiple sensors should be used to reliably track a target in all directions over a wide range. In this paper, we proposed a new method for combining multiple inaccurate skeleton data sets obtained from multiple sensors that capture a target from different angles into a single accurate skeleton data. The proposed algorithm uses density-based spatial clustering of applications with noise (DBSCAN) to prevent noise-added inaccurate joint candidates from participating in the merging process. After merging with the inlier candidates, we used Kalman filter to denoise the tremble error of the joint's movement. We evaluated the proposed algorithm's performance using the best view as the ground truth. In addition, the results of different sizes for the DBSCAN searching area were analyzed. By applying the proposed algorithm, the joint position accuracy of the merged skeleton improved as the number of sensors increased. Furthermore, highest performance was shown when the searching area of DBSCAN was 10 cm.


Subject(s)
Algorithms , Musculoskeletal System , Humans , Movement , Skeleton
3.
Mar Drugs ; 17(1)2019 Jan 11.
Article in English | MEDLINE | ID: mdl-30641942

ABSTRACT

Bisphosphonates (BPs) used for treating skeletal diseases can induce bisphosphonate-related osteonecrosis of the jaw (BRONJ). Despite much effort, effective remedies are yet to be established. In the present study, we investigated the feasibility of polydeoxyribonucleotide (PDRN) extracted from salmon sperm for the treatment of BRONJ, in a BRONJ-induced rat model. Compared with BRONJ-induced samples, PDRN-treated samples exhibited lower necrotic bone percentages and increased numbers of blood vessels and attached osteoclast production. Moreover, local administration of PDRN at a high concentration (8 mg/kg) remarkably resolved the osteonecrosis. Findings from this study suggest that local administration of PDRN at a specific concentration may be considered clinically for the management of BRONJ.


Subject(s)
Biological Products/pharmacology , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Polydeoxyribonucleotides/pharmacology , Salmon , Spermatozoa/chemistry , Administration, Topical , Aminopropionitrile/analogs & derivatives , Aminopropionitrile/toxicity , Animals , Biological Products/isolation & purification , Biological Products/therapeutic use , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Bisphosphonate-Associated Osteonecrosis of the Jaw/pathology , Bone and Bones/blood supply , Bone and Bones/drug effects , Bone and Bones/pathology , Disease Models, Animal , Drug Evaluation, Preclinical , Humans , Male , Osteoclasts/drug effects , Polydeoxyribonucleotides/isolation & purification , Polydeoxyribonucleotides/therapeutic use , Rabbits , Treatment Outcome
4.
Annu Int Conf IEEE Eng Med Biol Soc ; 2019: 542-545, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31945957

ABSTRACT

Gait is an important indicator for specific diseases. Abnormal gait patterns are caused by various factors such as physical, neurological, and sensory problems. If it is possible to recognize abnormal gait patterns in the early stage of the related disease, patients can receive proper treatment early and prevent secondary accidents such as falls caused by unbalanced gait. In this paper, we propose a gait recognition system that can recognize 5 abnormal gait patterns. Our system using 3D joint information obtained by using multiple Kinect v2 sensors and RNN-LSTM. In particular, abnormal gaits caused by physical problems such as injury, weakness of muscle, and joint problems are targeted for recognition. The purpose of this paper is to find optimal condition for gait recognition when using the multiple Kinect v2 sensors. Experiments were conducted by comparing the test accuracies on 14 combinations of human joint. Through this experiment, we selected optimal joints to show outstanding results so that our gait recognition model performs optimally. Results show that Ankles, Wrists, and the Head are the most influential joints on RNN-LSTM model. We applied 25-joint information of the human body to recognize gait patterns and achieved an accuracy over 97%.


Subject(s)
Gait , Ankle , Biomechanical Phenomena , Humans
5.
Maxillofac Plast Reconstr Surg ; 40(1): 38, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30588475

ABSTRACT

BACKGROUND: Fibrous dysplasia (FD) is a benign bone lesion characterized by the progressive replacement of normal bone with fibro-osseous connective tissue. The maxilla is the most commonly affected area of facial bone, resulting in facial asymmetry and functional disorders. Surgery is an effective management option and involves removing the diseased bone via an intraoral approach: conservative bone shaving or radical excision and reconstruction. CASE PRESENTATION: This case report describes a monostotic fibrous dysplasia in which the patient's right midface had a prominent appearance. The asymmetric maxillary area was surgically recontoured via the midfacial degloving approach under general anesthesia. Follow-up photography and radiographic imaging after surgery showed the structures were in a stable state without recurrence of the FD lesion. Furthermore, there were no visible scars or functional disability, and the patient reported no postoperative discomfort. CONCLUSIONS: In conclusion, the midfacial degloving approach for treatment of maxillary fibrous dysplasia is a reliable and successful treatment option. Without visible scars and virtually free of postoperative functional disability, this approach offers good exposure of the middle third of the face for treatment of maxillary fibrous dysplasia with excellent cosmetic outcomes.

6.
J Korean Assoc Oral Maxillofac Surg ; 44(5): 242-247, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30402417

ABSTRACT

Ameloblastoma treatment varies based on the clinical, histopathologic, and radiographic characteristics. Aggressive surgical treatments, such as marginal or segmental resection, have traditionally been implemented, but some conservative surgical methods are also being introduced, including decompression, enucleation, or curettage. The aim of the present study was to evaluate the possibility of applying these conservative surgical treatments to ameloblastoma and to analyze the prognosis of the procedures and their healing aspects. Among all patients who visited our clinic (Department of Oral and Maxillofacial Surgery, Kyung Hee University Dental Hospital at Gangdong) from 2009 to 2017, three who had undergone conservative surgery were recruited. One of these three patients underwent both excision of the lesion and an iliac bone graft during the same procedure. In the other two patients, due to the size of the lesion, decompression was performed to reduce the size of the lesion, and then conservative surgical treatments followed. As shown in the cases of this study, patients were only treated with conservative surgical methods, such as decompression or enucleation. During the follow-up period, there were no recurrences. In conclusion, the use of conservative surgical treatment in ameloblastoma can be a reliable, safe, and successful method.

7.
Mar Drugs ; 16(10)2018 Sep 25.
Article in English | MEDLINE | ID: mdl-30257482

ABSTRACT

Bone tissue engineering scaffolds offer the merits of minimal invasion as well as localized and controlled biomolecule release to targeted sites. In this study, we prepared injectable hydrogel systems based on visible light-cured glycol chitosan (GC) hydrogels containing bone morphogenetic protein-2 (BMP-2) and/or transforming growth factor-beta1 (TGF-ß1) as scaffolds for bone formation in vitro and in vivo. The hydrogels were characterized by storage modulus, scanning electron microscopy (SEM) and swelling ratio analyses. The developed hydrogel systems showed controlled releases of growth factors in a sustained manner for 30 days. In vitro and in vivo studies revealed that growth factor-loaded GC hydrogels have no cytotoxicity against MC3T3-E1 osteoblast cell line, improved mRNA expressions of alkaline phosphatase (ALP), type I collagen (COL 1) and osteocalcin (OCN), and increased bone volume (BV) and bone mineral density (BMD) in tibia defect sites. Moreover, GC hydrogel containing BMP-2 (10 ng) and TGF-ß1 (10 ng) (GC/BMP-2/TGF-ß1-10 ng) showed greater bone formation abilities than that containing BMP-2 (5 ng) and TGF-ß1 (5 ng) (GC/BMP-2/TGF-ß1-5 ng) in vitro and in vivo. Consequently, the injectable GC/BMP-2/TGF-ß1-10 ng hydrogel may have clinical potential for dental or orthopedic applications.


Subject(s)
Bone Morphogenetic Protein 2/pharmacology , Osteogenesis/drug effects , Tissue Scaffolds/chemistry , Transforming Growth Factor beta1/pharmacology , Wounds and Injuries/therapy , Animals , Bone Morphogenetic Protein 2/therapeutic use , Cell Differentiation/drug effects , Cell Line , Chitosan/chemistry , Delayed-Action Preparations , Disease Models, Animal , Drug Liberation , Drug Synergism , Humans , Hydrogels/chemistry , Light , Male , Osteoblasts , Rats , Rats, Wistar , Tibia/diagnostic imaging , Tibia/injuries , Transforming Growth Factor beta1/therapeutic use , Treatment Outcome , Wounds and Injuries/diagnostic imaging , X-Ray Microtomography
8.
Drug Deliv ; 25(1): 1664-1671, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30183420

ABSTRACT

Systemic drug delivery systems (SDDSs) for thyroid cancer treatment are associated with serious side effects including nausea, anorexia, and hair loss as a result of damage to normal tissues. In this study, we investigated the feasibility of a local DDS (LDDS) based on visible light-cured glycol chitosan (GC) hydrogel and doxorubicin⋅hydrochloride (DOX⋅HCl), called GC10/DOX, on thyroid cancer treatment in vivo. Visible light irradiation increased the storage modulus and swelling ratio of the GC10/DOX hydrogel precursor. The release of DOX⋅HCl from GC10/DOX exhibited two unique patterns comprising an initial burst within 18 hours, followed by a controlled and sustained release thereafter. In vitro cell viability testing showed that GC10/DOX had a greater antitumor effect than free DOX⋅HCl and GC10 hydrogel controls. In vivo, local injection of GC10/DOX near tumor tissue led to a superior antitumor effect compared with controls consisting of free DOX⋅HCl intravenously injected to the tail vein of thyroid cancer-bearing mouse and GC10 hydrogel subcutaneously injected near the tumor. Altogether, our results suggest that GC10/DOX may have clinical potential for thyroid cancer treatment.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Chitosan , Doxorubicin/administration & dosage , Drug Delivery Systems , Thyroid Neoplasms/drug therapy , Animals , Cell Line, Tumor , Chitosan/chemistry , Humans , Light , Male , Mice , Mice, Inbred BALB C
9.
Exp Ther Med ; 16(1): 400-405, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29896266

ABSTRACT

Bisphosphonates are generally used as therapeutic agents for bone diseases. However, previous reports on bisphosphonates-related osteonecrosis of the jaw (BRONJ) demonstrated that inflammation triggers and worsens the disease. Recently, polydeoxynucleotide (PDRN), an A2A receptor agonist, has been suggested for the treatment of various diseases and broadly studied for its anti-inflammatory effect. The present study aimed to measure the effect of PDRN on macrophage cells treated with zoledronic acid (ZA) and lipopolysaccharide (LPS). Macrophage cells were cultured with ZA for 24 h, following which they were stimulated with LPS in the presence or absence of varying concentrations of PDRN for 24 h. The cell viability and nitric oxide (NO) production of the cells were analyzed. In addition, protein expression levels were quantified by western blotting. Cell viability was compromised and NO was overexpressed by ZA and LPS stimulation. However, under ZA and LPS stimulation cell viability was enhanced, and NO production, and inducible nitric oxide synthase, interleukin (IL)-1ß, -6, and tumor necrosis factor-α overexpression were suppressed on exposure to PDRN. A2A receptor and vascular endothelial growth factor (VEGF) expression levels increased following PDRN treatment. These results indicate that PDRN treatment of macrophages inhibits the inflammatory cytokines induced by ZA and LPS stimulation. It was hypothesized that the inflammatory cytokines were inhibited through A2A activation by PDRN. In addition, increased VEGF expression may contribute to increased vascularization and subsequently improve the pathological condition in BRONJ. As inflammation and LPS may stimulate the occurrence of BRONJ, the present study postulated that PDRN is possibly a candidate for the therapeutic management of BRONJ by decreasing inflammation and increasing vascularization.

10.
Artif Cells Nanomed Biotechnol ; 46(sup2): 874-882, 2018.
Article in English | MEDLINE | ID: mdl-29749265

ABSTRACT

Currently available chemotherapy is associated with serious side effects, and therefore novel drug delivery systems (DDSs) are required to specifically deliver anticancer drugs to targeted sites. In this study, we evaluated the feasibility of visible light-cured glycol chitosan (GC) hydrogels with controlled release of doxorubicin⋅hydrochloride (DOX⋅HCl) as local DDSs for effective cancer therapy in vivo. The storage modulus of the hydrogel precursor solutions was increased as a function of visible light irradiation time. In addition, the swelling ratio of the hydrogel irradiated for 10 s (GC10/DOX) was greater than in 60 s (GC60/DOX). In vitro release test showed that DOX was rapidly released in GC10/DOX compared with GC60/DOX due to the density of cross-linking. In vitro and in vivo tests including cell viability and measurement of tumor volume showed that the local treatment of GC10/DOX yielded substantially greater antitumor effect compared with that of GC60/DOX. Therefore, the visible light-cured GC hydrogel system may exhibit clinical potential as a local DDS of anticancer drugs with controlled release, by modulating cross-linking density.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Chitosan/chemistry , Doxorubicin/chemistry , Doxorubicin/pharmacology , Hydrogels/chemistry , Light , Animals , Cell Survival/drug effects , Delayed-Action Preparations , Feasibility Studies , Humans , Injections , MCF-7 Cells , Mice , Xenograft Model Antitumor Assays
11.
Molecules ; 22(9)2017 Sep 10.
Article in English | MEDLINE | ID: mdl-28891961

ABSTRACT

Scarless wound healing is ideal for patients suffering from soft tissue defects. In this study, we prepared a novel wet dressing (ß-CD-ic-CUR/GC) based on the visible light-cured glycol chitosan (GC) hydrogel and inclusion complex between beta-cyclodextrin (ß-CD) and curcumin (CUR). We also evaluated its efficacy in the acceleration of wound healing as compared to that of CUR-loaded GC (CUR/GC). The conjugation of glycidyl methacrylate (GM) to GC for photo-curing was confirmed by ¹H-NMR measurement, and the photo-cured GC hydrogel was characterized by the analyses of rheology, swelling ratio, SEM and degradation rate. After visible light irradiation, the surface/cross-sectional morphologies and storage (G')/loss (G'') moduli revealed the formation of hydrogel with interconnected porosity. The dressing ß-CD-ic-CUR/GC exhibited a controlled release of 90% CUR in a sustained manner for 30 days. On the other hand, CUR/GC showed CUR release of 16%. ß-CD acted as an excipient in improving the water-solubility of CUR and affected the release behavior of CUR. The in vivo animal tests including measurement of the remaining unhealed wound area and histological analyses showed that ß-CD-ic-CUR/GC may have potential as a wet dressing agent to enhance soft tissue recovery in open fractures.


Subject(s)
Bandages, Hydrocolloid , Curcumin/pharmacology , Delayed-Action Preparations/pharmacology , Hydrogels/pharmacology , Surgical Wound/drug therapy , Wound Healing/drug effects , Animals , Cell Line , Cell Proliferation/drug effects , Chitosan/chemistry , Curcumin/chemistry , Curcumin/pharmacokinetics , Delayed-Action Preparations/chemical synthesis , Delayed-Action Preparations/pharmacokinetics , Delayed-Action Preparations/radiation effects , Drug Liberation , Epoxy Compounds/chemistry , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/metabolism , Hydrogels/chemical synthesis , Hydrogels/pharmacokinetics , Hydrogels/radiation effects , Light , Methacrylates/chemistry , Mice , Mice, Inbred BALB C , Photochemical Processes , Surgical Wound/pathology , Wound Healing/physiology , beta-Cyclodextrins/chemistry
12.
Int J Mol Sci ; 18(8)2017 Aug 03.
Article in English | MEDLINE | ID: mdl-28771196

ABSTRACT

The most ideal implant models in the dental and orthopedic fields to minimize the failure rate of implantation involve the improvement of osseointegration with host bone. Therefore, a focus of this study is the preparation of surface-modified titanium (Ti) samples of disc and screw types using dexamethasone (DEX) and/or growth and differentiation factor-5 (GDF-5), as well as the evaluation of their efficacies on bone formation in vitro and in vivo. X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and contact angle measurement were used to evaluate the surface chemical composition, surface morphology and wettability, respectively. The results showed that implant surfaces were successfully modified with DEX and/or GDF-5, and had rough surfaces along with hydrophilicity. DEX, GDF-5 or DEX/GDF-5 on the surface-modified samples were rapidly released within one day and released for 28 days in a sustained manner. The proliferation and bone formation of MC3T3-E1 cells cultured on pristine and surface-modified implants in vitro were examined by cell counting kit-8 (CCK-8) assay, as well as the measurements of alkaline phosphatase (ALP) activity and calcium deposition, respectively. MC3T3-E1 cells cultured on DEX/GDF-5-Ti showed noticeable ALP activity and calcium deposition in vitro. Active bone formation and strong osseointegration occurred at the interface between DEX/GDF-5-Ti and host bone, as evaluated by micro computed-tomography (micro CT) analysis. Surface modification using DEX/GDF-5 could be a good method for advanced implants for orthopaedic and dental applications.


Subject(s)
Coated Materials, Biocompatible , Dexamethasone , Growth Differentiation Factor 5 , Heparin , Osteogenesis/drug effects , Titanium , beta-Cyclodextrins , Animals , Antigens, Differentiation/biosynthesis , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Dexamethasone/chemistry , Dexamethasone/pharmacology , Growth Differentiation Factor 5/chemistry , Growth Differentiation Factor 5/pharmacology , Heparin/chemistry , Heparin/pharmacology , Humans , Mice , Rabbits , Titanium/chemistry , Titanium/pharmacology , beta-Cyclodextrins/chemistry , beta-Cyclodextrins/pharmacology
13.
Int Neurourol J ; 21(Suppl 1): S39-47, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28446017

ABSTRACT

PURPOSE: Dexmedetomidine, an α2-adrenergic agonist, provides sedative and analgesic effects without significant respiratory depression. Dexmedetomidine has been suggested to have an antiapoptotic effect in response to various brain insults. We developed an oral mucosa patch using dexmedetomidine for sedation. The effects of the dexmedetomidine oral mucosa patch on cell proliferation and apoptosis in the hippocampus were evaluated. METHODS: A hydrogel oral mucosa patch was adhered onto the oral cavity of physiologically normal rats, and was attached for 2 hours, 6 hours, 12 hours, or 24 hours. Plasma dexmedetomidine concentrations were determined by liquid chromatography- electrospray ionization-tandem mass spectrometry-multiple-ion reaction monitoring (LC-ESI-MS/MS-MRM). Cell proliferation in the hippocampus was detected by Ki-67 immunohistochemistry. Caspase-3 immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, and Western blotting for Bax and Bcl-2 were performed to detect hippocampal apoptosis. The levels of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) in the hippocampus were also measured by Western blotting. RESULTS: Plasma dexmedetomidine concentration increased according to the attachment time of the dexmedetomidine oral mucosa patch. Hippocampal cell proliferation did not change due to the dexmedetomidine oral mucosa patch, and the dexmedetomidine oral mucosa patch exerted no significant effect on BDNF or TrkB expression. In contrast, the dexmedetomidine oral mucosa patch exerted an antiapoptotic effect depending on the attachment time of the dexmedetomidine oral mucosa patch. CONCLUSIONS: A dexmedetomidine oral mucosa patch can be used as a convenient tool for sedation, and is of therapeutic value due to its antiapoptotic effects under normal conditions.

14.
Int J Mol Sci ; 18(1)2017 Jan 23.
Article in English | MEDLINE | ID: mdl-28124978

ABSTRACT

In this study, we prepared human bone morphogenetic protein-2 (hBMP-2)/human growth and differentiation factor-5 (hGDF-5)-coated titanium (Ti) disc and screw types for controlled release of the growth factors (GFs). The two growth factors were coated onto Ti with a smooth surface using their specific interaction with heparin, because they have heparin binding sites in their molecular structures. Efficacy of the two growth factor-coated Ti for enhancement of bone formation and osseointegration was compared to pristine Ti, and hBMP-2- and hGDF-5-coated Ti in vivo. The surface chemical composition, surface morphology, and wettability characteristics of the metal samples were determined by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and contact angle measurement, respectively. The initial burst of hBMP-2, hGDF-5, and their combination, occurred within one day of the release study, resulting in 12.5%, 4.5%, and 13.5%/3.2%, and then there was a sustained, even release of these two growth factors from the coated metal for 30 days. In vitro tests revealed that MC3T3-E1 cells cultured on the two growth factor-coated Ti had a higher proliferation rate and a higher activity for alkaline phosphatase (ALP), which led to a larger amount of calcium deposition and larger expressions of type I collagen (COL 1), ALP, and osteocalcin (OCN) mRNAs. In vivo animal tests using ten white New Zealand rabbits showed that the two growth factor-coated Ti enhanced bone formation and osseointegration at the interface between the implants and host bone. In addition, histological evaluation showed that bone remodeling, including bone formation by osteoblasts and bone resorption by osteoclasts, actively occurred between the two growth factor-coated Ti and host bone. Consequently, it is suggested that Ti surface modification with the combination of hBMP-2 and hGDF-5 for the two growth factor-coated Ti implants can improve the clinical properties of implants for orthopedic and dental applications.


Subject(s)
Bone Morphogenetic Protein 2/pharmacology , Dental Implants , Growth Differentiation Factor 5/pharmacology , Heparin/chemistry , Titanium/pharmacology , Alkaline Phosphatase/metabolism , Animals , Calcium/metabolism , Cell Line , Cell Proliferation/drug effects , Gene Expression Regulation/drug effects , Humans , Mice , Microscopy, Fluorescence , Photoelectron Spectroscopy , RNA, Messenger/genetics , RNA, Messenger/metabolism , Surface Properties , Titanium/chemistry , Water/chemistry , X-Ray Microtomography
15.
J Nanosci Nanotechnol ; 17(1): 143-52, 2017 Jan.
Article in English | MEDLINE | ID: mdl-29617095

ABSTRACT

In the present study, we evaluated the potential of poly-l-lysine/hyaluronic acid (HA/PLL) hydrogels containing curcumin (CUR) and bone morphogenetic protein-2 (BMP-2) as bone tissue regeneration scaffolds. Hydrogels HP-1˜2 were formed by amide bonds via the condensation reactions between 0.02 µmol HA and 0.06­0.12 µmol poly-l-lysine · hydrobromide (PLL · HBr). Physical, chemical, and thermal analyses revealed that the amount of PLL · HBr significantly influenced hydrogel properties. Based on an In Vitro MG-63 cell proliferation test, HP-1˜2 were cytocompatible, and all hydrogels containing different amounts of CUR and BMP-2, except for HA0.02/PLL0.06/CUR20/BMP-2100 (HPCB-4), resulted in cell proliferation above 80%. An In Vitro release test showed that CUR and BMP-2 were consistently released from HA0.02/PLL0.06/CUR15 (HPC), HA0.02/PLL0.06/BMP-2100 (HPB), HA0.02/PLL0.06/CUR15/BMP-210 , 50 , or 100 (HPCB-1˜3), and HA0.02/PLL0.06/CUR10 or 20/BMP-2100 (HPCB-4˜5) for 7 and 28 days, respectively. In Vitro ALP activity and calcium deposition and In Vivo micro-computed tomography (micro-CT) tests demonstrated the potential application of HPCB-3 as bone tissue regeneration scaffolds, suggesting that bone tissue regeneration can be optimized by controlling the amounts of CUR and BMP-2.


Subject(s)
Bone Morphogenetic Protein 2/pharmacology , Curcumin/pharmacology , Osteogenesis/drug effects , Tissue Engineering/methods , Animals , Bone Regeneration/drug effects , Hyaluronic Acid/chemistry , Hydrogels/chemistry , Mice , Polylysine/chemistry , Tissue Scaffolds/chemistry , X-Ray Microtomography
16.
J Nanosci Nanotechnol ; 17(1): 217-23, 2017 Jan.
Article in English | MEDLINE | ID: mdl-29617547

ABSTRACT

Simvastatin (SIM) accelerates new bone formation both in vitro and In Vivo by enhancing the expression of recombinant human bone morphogenetic protein-2 (rhBMP-2). In this study, we evaluated the effect of water-solubility of SIM on new bone formation by preparing two types of supramolecular hydrogels: pseudopolyrotaxanes (PPRXs) based on metoxy polyethyleneglycol-grafted hyaluronic acid (MPEG-g-HA) and α-cyclodextrin (α-CD) containing water-soluble hydroxypropyl ß-cyclodextrin/simvastatin inclusion complex (HP-ß-CD-ic-SIM; MPEG-g-HA/α-CD/HP-ß-CD-ic-SIM) or only SIM (MPEG-g-HA/α-CD/SIM). As compared to MPEG-g- HA/α-CD/SIM, SIM was more rapidly released from MPEG-g-HA/α-CD/HP-ß-CD-ic-SIM in a sustained manner owing to increased water-solubility. New bone actively formed at the calvarial defect site in a rabbit model 4 weeks after implantation, as examined by micro computed tomography (micro CT), hematoxylin and eosin (H&E) staining, and Goldner's trichrome staining. The results showed that the water-solubility of SIM plays a significant role in enhancing new bone formation in vivo.


Subject(s)
Cyclodextrins/chemistry , Hyaluronic Acid/chemistry , Hydrogels/chemistry , Osteogenesis/drug effects , Poloxamer/chemistry , Rotaxanes/chemistry , Simvastatin , Animals , Humans , Mice , Simvastatin/chemistry , Simvastatin/pharmacokinetics , Simvastatin/pharmacology , Skull/diagnostic imaging , Skull/drug effects , Solubility
17.
J Nanosci Nanotechnol ; 17(2): 998-1007, 2017 Feb.
Article in English | MEDLINE | ID: mdl-29671974

ABSTRACT

In this study we report on the effectiveness of click chemistry-enhanced zirconium dioxide (ZrO2-3) for the immobilization of biomolecules, and the enhancement of osteoblastic differentiation of MC3T3-E1 cells by bone morphogenetic protein-2 (BMP-2) immobilized on ZrO2-6. The surfaces of ZrO2-1 through 6 were characterized by scanning electron microscopy (SEM), static contact angles, and X-ray photoelectron spectroscopy (XPS) measurements. The results from these tests indicated that ZrO2-1 was successfully surface-modified via click chemistry (ZrO2-3). Through quantitative analysis of heparin immobilized on ZrO2-5, we found that ZrO2-3 was a useful tool for immobilizing biomolecules such as heparin. Release tests of BMP-2 from ZrO2-6 showed well-controlled release kinetics over a period of 28 days. MC3T3-E1 cell proliferation tests indicated that ZrO2-6 was highly biocompatible with these cells. Through In Vitro tests such as alkaline phosphatase (ALP) activity, calcium deposition, and real-time polymerase chain reaction (real-time PCR), we found that ZrO2-6 was a useful tool for enhancing osteoblastic differentiation of MC3T3-E1 cells.


Subject(s)
Bone Morphogenetic Protein 2/pharmacology , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Osteogenesis/drug effects , Zirconium/chemistry , Animals , Bone Morphogenetic Protein 2/chemistry , Bone Morphogenetic Protein 2/pharmacokinetics , Cell Line , Click Chemistry , Heparin , Mice , Nanotechnology
18.
Carbohydr Polym ; 157: 1750-1758, 2017 Feb 10.
Article in English | MEDLINE | ID: mdl-27987891

ABSTRACT

In this study, we designed a hybrid Ti by heparin modifying the Ti surface followed by Growth/differentiation factor-5 (GDF-5) loading. After that, products were characterized by physicochemical analysis. Quantitative analysis of functionalized groups was also confirmed. The release behavior of GDF-5 grafted samples was confirmed for up to 21days. The surface modification process was found to be successful and to effectively immobilize GDF-5 and provide for its sustained release behavior. As an in vitro test, GDF-5 loaded Ti showed significantly enhanced osteogenic differentiation with increased calcium deposition under nontoxic conditions against periodontal ligament stem cells (PDLSc). Furthermore, an in vivo result showed that GDF-5 loaded Ti had a significant influence on new bone formation in a rabbit model. These results clearly confirmed that our strategy may suggest a useful paradigm by inducing osseo-integration as a means to remodeling and healing of bone defects for restorative procedures in dentistry.


Subject(s)
Dental Implants , Growth Differentiation Factor 5/pharmacology , Heparin/chemistry , Osteogenesis/drug effects , Animals , Cell Differentiation , Cells, Cultured , Humans , Periodontal Ligament/cytology , Rabbits , Stem Cells/drug effects , Surface Properties , Titanium
19.
Dent Mater ; 32(11): 1301-1311, 2016 11.
Article in English | MEDLINE | ID: mdl-27634479

ABSTRACT

OBJECTIVE: Magnetic biomaterials have recently gained great attention due to their some intriguing cell and tissue responses. However, little attention has been given to the fields of dental tissue regeneration. In this sense, we aim to investigate the effects of magnetic nanofiber scaffolds on the human dental pulp cell (HDPC) behaviors and to elucidate the underlying signaling mechanisms in the events. METHODS: Magnetic nanofiber scaffolds incorporating magnetic nanoparticles at varying contents were prepared into nanofibrous matrices to cultivate cells. Cell growth by MTS assay, odontoblastic differentiation by alkaline phosphatase (ALP) activity, mineralization, and the mRNA expression of differentiation-related genes of HDPCs, in vitro angiogenesis by migration and capillary tube formation in endothelial cells on the conditioned medium obtained from HDPSCs in the presence or absence of scaffolds. Western blot analysis and confocal immunofluorescene were used to asses signaling pathways. RESULTS: The growth of HDPCs was significantly enhanced on the magnetic scaffolds with respect to the non-magnetic counterpart. The odontogenic differentiation of cells was significantly up-regulated by the culture with magnetic scaffolds. Furthermore, the magnetic scaffolds promoted the HDPC-induced angiogenesis of endothelial cells. The expression of signaling molecules, Wnt3a, phosphorylated GSK-3ß and nuclear ß-catenin, was substantially stimulated by the magnetic scaffolds; in parallel, the MAPK and NF-κB were highly activated when cultured on the magnetic nanofiber scaffolds. SIGNIFICANCE: This study is the first to demonstrate that magnetic nanofiber scaffolds stimulate HDPCs in the events of growth, odontogenic differentiation, and pro-angiogenesis, and the findings imply the novel scaffolds can be potentially useful as dentin-pulp regenerative matrices.


Subject(s)
Dental Pulp/metabolism , NF-kappa B/metabolism , Nanofibers , Neovascularization, Physiologic , Odontogenesis , Cell Differentiation , Humans , Mitogen-Activated Protein Kinase Kinases/metabolism , Wnt Proteins/metabolism
20.
J Nanosci Nanotechnol ; 16(1): 280-6, 2016 Jan.
Article in English | MEDLINE | ID: mdl-27398455

ABSTRACT

Zirconia (Zr) is also known as a biocompatible material with favorable mechanical properties as well as low plaque adhesion. In this study, we examined the efficacy of Zr coated with growth and differentiation factor-5 (GDF-5) bonded via click reaction as a substrate to support osteogenic differentiation of MC3T3-E1 cells. Pristine and surface-modified Zr surfaces were characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), resulting that GDF-5 was successfully coated to the pristine Zr surface. GDF-5 coated to Zr surfaces was released for 28 days in a sustained manner. New bone formation onto GDF-5 coated Zr (Zr/GDF-5) surface was confirmed by in vitro test including cell proliferation, alkaline phosphatase activity and calcium deposition assays, and in vivo test including real-time polymerase chain reaction (qPCR) assay including osterix (OSX), runt-related transcription factor 2 (Runx 2), COL 1 (type I collagen) and osteocalcin (OC). Cell proliferation, alkaline phosphatase activity, and calcium deposition of MC3T3- E1 cells were significantly enhanced when the cells were cultured on Zr/GDF-5. Additionally, the results of qPCR revealed that genes related with osteogenic differentiation were up regulated when the cells were cultured on Zr/GDF-5. Our findings demonstrate that Zr/GDF-5 could be used as a material for enhancing the efficacy of osteogenic differentiation.


Subject(s)
Cell Differentiation/drug effects , Coated Materials, Biocompatible , Growth Differentiation Factor 5 , Nanoparticles/chemistry , Osteogenesis/drug effects , Zirconium , Animals , Cell Line , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Growth Differentiation Factor 5/chemistry , Growth Differentiation Factor 5/pharmacology , Mice , Zirconium/chemistry , Zirconium/pharmacology
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