Showing papers in "Biomaterials Research in 2014"

Nanofibrous scaffolds in biomedical applications.

Abstract: Nanofibrous scaffolds are artificial extracellular matrices which provide natural environment for tissue formation. In comparison to other forms of scaffolds, the nanofibrous scaffolds promote cell adhesion, proliferation and differentiation more efficiently due to having high surface to volume ratio. Although scaffolds for tissue engineering have been fabricated by various techniques but electrospun nanofibrous scaffolds have shown great potential in the fields of tissue engineering and regeneration. This review highlights the applications and importance of electrospun nanofibrous scaffolds in various fields of biomedical applications ranging from drug delivery to wound healing. Attempts have also been made to highlights the advantages and disadvantages of nanofirbous scaffolds fabricated for biomedical applications using technique of electrospinning. The role of various factors controlling drug distribution in electrospun nanofibrous scaffolds is also discussed to increase the therapeutic efficiency of nanofibrous scaffolds in wound healing and drug delivery applications.

Polymeric nanocarrier systems for photodynamic therapy.

Abstract: Photodynamic therapy (PDT) is an emerging treatment modality that involves the combined action of photosensitizers (PSs) and light for treatment of solid tumor and other diseases. Although this therapeutic method has been considered as an alternative to classical cancer treatments, clinical PDT requires further advances in selectivity and therapeutic efficacy to overcome numerous shortages related to conventional PDT. In this regard, great efforts have been devoted to the development of polymeric nanocarrier-encapsulated PSs for targeted PDT, aiming at improvement of water solubility and tumor-specificity of hydrophobic PSs. Here, we discuss the general concepts and considerations of polymeric nanocarriers for efficient delivery of PSs. In recent, the amphiphilic PS-polymer conjugate-based self-quenchable nanoparticles and PS-polymer-conjugate/quencher nanocomplexes have emerged as an attractive delivery platform for efficient and reliable PDT. They can incorporate and deliver the PS in a photodynamically inactive state but demonstrate cytotoxic effects by tumor environment-sensitive activation mechanisms, so that the photodynamic cancer treatment can achieve maximum target specificity. Here, we report the recent achievements on the development of activatable PS formulations based on PS-polymer conjugates.

New approach for the treatment of osteoradionecrosis with pentoxifylline and tocopherol

Abstract: Osteoradionecrosis (ORN) of the jaw is a significant complication of radiotherapy for oral cavity cancer. In addition to antibiotic medication, treatment options such as hyperbaric oxygen therapy, surgical approaches, and combined therapy with pentoxifylline and tocopherol have been recently introduced. In this review article, we will discuss the definition and classifications of osteoradionecrosis, its etiology and pathophysiology, previous treatment options, oral and maxillofacial complications of radiotherapy, basic information on pentoxifylline and tocopherol, recent reports of pentoxifylline and tocopherol combined therapy, and, finally, ORN-induced animal models and future approaches.

Purification and Biocompatibility of Fermented Hyaluronic Acid for Its Applications to Biomaterials

Abstract: Hyaluronic acid (HA) is of importance due to its diverse applications in pharmaceuticals and medical devices such as dermal filler, adhesion barriers, carrier for cells and bioactive molecules as well as scaffold biomaterials for tissue engineering. Evaluations of purification and biocompatibility of HA are required for its applications to biomaterials. After synthesizing HA by fermentation of streptococcus zooepidemicus for 25 hr, extensively purification of the fermented broth was performed to remove impurities using a filtration process for insoluble components and cells, and diverse adsorbents for soluble impurities. Its in vitro biocompatibility has been evaluated by measurement of cell counting and assay of cell live and dead. 60% yield of white HA powder was obtained, having 15–17 dL/g intrinsic viscosity with a molecular weight of approximately 1,000 kDa. While low molecular weight impurities and insoluble impurities were successfully removed using a ultrafiltration membrane with 50 KDa molecular weight cut, endotoxins, high molecular weight proteins and nucleic acids were removed from the broth by employing adsorbents such as alumina and activated carbons. Alumina showed the best results for the removal of endotoxins, all of the activated carbons were very effective in the removal of high molecular weight proteins and nucleic acids. The purified HA solution showed excellent cell compatibility with no cell damages as observed by both measurement of cell proliferation and observation of cell viability. We obtained high molecular weight HA with excellent biocompatibility as judged by both measurement of cell proliferation and viability, indicating high possibility of its applications to biomaterials.

Adult stem cells and tissue engineering strategies for salivary gland regeneration: a review

Abstract: Saliva is an important compound produced by the salivary glands and performs numerous functions. Hyposalivation (dry mouth syndrome) is a deleterious condition often resulting from radiotherapy for patients with head and neck cancer, Sjogren’s Syndrome, or as a side effect of certain medications. Hyposalivation negatively affects speaking, mastication, and swallowing in afflicted patients, greatly reducing their quality of life. Current treatments for this pathology include modifying lifestyle, synthetic saliva supplementation, and the utilization of salivary gland stimulants and sialagogues. However, many of these treatments do not address the underlying issues and others are pervaded by numerous side effects. In order to address the shortcomings related to current treatment modalities, many groups have diverted their attention to utilizing tissue engineering and regenerative medicine approaches. Tissue engineering is defined as the application of life sciences and materials engineering toward the development of tissue substitutes that are capable of mimicking the structure and function of their natural analogues within the body. The general underlying strategy behind the development of tissue engineered organ substitutes is the utilization of a combination of cells, biomaterials, and biochemical cues intended to recreate the natural organ environment. The purpose of this review is to highlight current bioengineering approaches for salivary gland tissue engineering and the adult stem cell sources used for this purpose. Additionally, future considerations in regard to salivary gland tissue engineering strategies are discussed.

Effect of porous polycaprolactone beads on bone regeneration: preliminary in vitro and in vivo studies

Abstract: Background: For the effective bone regeneration with appropriate pathological/physiological properties, a variety of bone fillers have been adapted as a therapeutic treatment. However, the development of ideal bone fillers is still remained as a big challenge in clinical practice. The main aims of this study are i) fabrication of a highly porous PCL beads; and ii) the estimation of the potential use of the porous PCL beads as a bone filler through preliminary animal study. Results: The porous PCL beads with size range of 53 ~ 600 μm (425 ~ 500 μm dominantly) are fabricated by a spray/precipitation method using a double nozzle spray and PCL solution (in tetraglycol). The PCL beads show highly porous inner pore structure and the pores are interconnected with outer surface pores. For the preliminary animal study, we recognize that the porous PCL bead can induce the new bone formation from the outer surface of bone defect toward the bone marrow cavity through the bead matrix. Conclusions: From the preliminary results, we can suggest that the highly porous PCL beads may be a promising candidate as a bone filler (scaffolding matrix) for the effective bone regeneration.

Genetically engineering encapsulin protein cage nanoparticle as a SCC-7 cell targeting optical nanoprobe

Abstract: Protein cage nanoparticles are promising nanoplatform candidates for efficient delivery systems of diagnostics and/or therapeutics because of their uniform size and structure as well as high biocompatibility and biodegradability. Encapsulin protein cage nanoparticle is used to develop a cell-specific targeting optical nanoprobe. FcBPs are genetically inserted and successfully displayed on the surface of encapsulin to form FcBP-encapsulin. Selectively binding of FcBP-encapsulin to SCC-7 is visualized with fluorescent microscopy. Encapsulin protein cage nanoparticle is robust enough to maintain their structure at high temperature and easily acquires multifunctions on demand through the combination of genetic and chemical modifications.

The market trend analysis and prospects of scaffolds for stem cells

Abstract: Scaffolds are one of the three most important elements constituting the basic concept of regenerative medicine, and are included in the core technology of regenerative medicine along with stem cells and tissue engineering. Stem cells are very important technology because they are directly responsible for the regenerative treatment of the disease and the damaged tissue, but with regards to the technology and the products that use stem cells exclusively, there is a technical limitation of limited survival rate and the engraftment rate of the transplanted cell, and rather than recovering the damaged tissue fundamentally, there is a limit that the concept is more of just another medicine treatment using cells. A scaffold is a natural or synthetic biocompatible material transplanted into a human body to be used as the exclusive treatment or as an assisted method of another treatment of a disease and for the recovery of damaged tissue. Therefore, according to the characteristics of the tissue to be applied, scaffolds must have the characteristics such as the excellent biocompatibility, biodegradability, minimum immunity and inflammation, proper mechanical strength and interaction between the material and the cells. The world stem cell market was approximately 2.715 billion dollars in 2010, and with a growth rate of 16.8% annually, a market of 6.877 billion dollars will be formed in 2016. From 2017, the expected annual growth rate is 10.6%, which would expand the market to 11.38 billion dollars by 2021. Meanwhile, the world scaffold element technology market was approximately 4.57 million dollars in 2013, and by increasing 13.4% annually, it is estimated to expand to 10.63 million dollars by 2020. The Korean scaffold element technology market was about 22 million dollars in 2013, and with a steady growth of approximately 13.4% every year, it is prospected to be about 52 million dollars by 2020. In comparison to the medical material and medicine sales growth rate, the future scaffold element technology market is judged to be higher in growth possibility.

Effect of osteoconductive hyaluronate hydrogels on calvarial bone regeneration

Abstract: Without exploitation of possibly immunogenic and carcinogenic bone morphogenetic protein, we developed simple but clinically feasible artificial bone graft using osteoconductive hyaluronate (HA) hydrogels and bioactive MegaGen synthetic bone (MGSB). HA hydrogels were synthesized by the crosslinking reaction between carboxyl groups of HA and amine groups of gelatin (GEL). Then, artificial bone grafts were prepared by mixing MGSB with HA-GEL hydrogels. The bone regeneration by the MGSB/HA-GEL hydrogel complex was assessed in the skull of New Zealand white male rabbits in 4 and 8 weeks. HA hydrogels were synthesized by the crosslinking reaction between carboxyl groups of HA and amine groups of gelatin (GEL). Then, artificial bone grafts were prepared by mixing MGSB with HA-GEL hydrogels. In vitro proliferation of preosteogenic cells was enhanced with increasing molecular weight of HA. In addition, histological analysis of dissected tissues with hematoxylin and eosin staining confirmed the effective in vivo bone regeneration by the MGSB/HA-GEL hydrogel complex. The MGSB/HA-GEL hydrogels were well resorbed and partially substituted to the lamellar bone after implantation for 8 weeks. The novel artificial bone graft of MGSB/HA-GEL hydrogel complex for effective bone regeneration might be clinically feasible for further development.

Polyurethane membrane with porous surface for controlled drug release in drug eluting stent

Abstract: Background: Membrane covered drug eluting stents (DES) were prepared to prevent tumor ingrowth and to control drug release. Polyurethane (PU) is commonly used for DES coating material because of high tensile strength. The release of paclitaxel (PTX) may increase from porous PU membrane. Results: Polyethylene glycol (PEG) was incorporated into PU membranes to form porous structure and control the release of hydrophobic anti-cancer drug such as PTX. The bare metal stents were coated with PEG incorporated PU and then, PEG was washed out to form porous structure. The crystallization of PTX was inhibited in porous PU membranes and the release of PTX from porous PU membranes was approximately 8.6% more extended over 19 days. Conclusions: The enhanced release of PTX from porous PU membranes may increase the patency for the DES covering materials.

Cell-adhesive RGD peptide-displaying M13 bacteriophage/PLGA nanofiber matrices for growth of fibroblasts.

Abstract: M13 bacteriophages can be readily fabricated as nanofibers due to non-toxic bacterial virus with a nanofiber-like shape. In the present study, we prepared hybrid nanofiber matrices composed of poly(lactic-co-glycolic acid, PLGA) and M13 bacteriophages which were genetically modified to display the RGD peptide on their surface (RGD-M13 phage). The surface morphology and chemical composition of hybrid nanofiber matrices were characterized by scanning electron microscopy (SEM) and Raman spectroscopy, respectively. Immunofluorescence staining was conducted to investigate the existence of M13 bacteriophages in RGD-M13 phage/PLGA hybrid nanofibers. In addition, the attachment and proliferation of three different types of fibroblasts on RGD-M13 phage/PLGA nanofiber matrices were evaluated to explore how fibroblasts interact with these matrices. SEM images showed that RGD-M13 phage/PLGA hybrid matrices had the non-woven porous structure, quite similar to that of natural extracellular matrices, having an average fiber diameter of about 190 nm. Immunofluorescence images and Raman spectra revealed that RGD-M13 phages were homogeneously distributed in entire matrices. Moreover, the attachment and proliferation of fibroblasts cultured on RGD-M13 phage/PLGA matrices were significantly enhanced due to enriched RGD moieties on hybrid matrices. These results suggest that RGD-M13 phage/PLGA matrices can be efficiently used as biomimetic scaffolds for tissue engineering applications.

Stimulated migration and penetration of vascular endothelial cells into poly (L-lactic acid) scaffolds under flow conditions

Abstract: The initial procedure of the development of engineered tissues is cell seeding into three-dimensional polymer scaffolds. However, it is hard to make the cells invade into scaffold due to the characteristic of pore and material. Electrospun poly (L-lactic acid) scaffold and flow perfusion system were used to overcome these seeding problems. Before starting the experiment, we set up the parallel plate chamber system to observe endothelial cell migration under flow condition. In individual cell migration model, human umbilical endothelial cells started to migrate in the direction of flow at 8 dyne/cm2 and we observed the cytoskeleton alignment at 8 dyne/cm2. This study has demonstrated the possibility to evaluate and analyze cell migration using the parallel plate chamber system and we may predict in vivo cell migration under flow condition based on these results. Also the flow perfusion system was established for the effective cell seeding into at three dimensional scaffolds. Moreover, shear stress induced by flow can enhance cell migration into PLLA scaffold that is in the form of cotton. Result indicated that cell penetration was achieved under flow condition better and more than under static condition throughout the matrix.

Recent trends on the stent research for blood arteries by bibliometric analysis

Abstract: The research trends on stent for blood arteries are reviewed by bibliometric analysis using 7,790 journal articles published from 1986 to 2013 of the Web of Science database. The bibliometric indicators are applied to analyze the journal article data, which are simple number of publications for selecting key players, citation indicators for measuring qualitative research performance, collaboration indicators for figuring out the degree of international collaboration and keyword mapping for identifying the research trends. The studies of stent for blood arteries are investigated on the basis of the analysis by countries, institutions and topic changing. The leading countries and institutions published many high-quality journal articles with strong international collaboration. In this report, the current status and future of research trends are clearly revealed from the periodic topic changing analysis. The keywords such as ‘drug eluting stent’, ‘stent coated with new polymers’ and ‘drug delivery systems’ have come into the recent stent-related research, which means lots of efforts are under way to overcome the present limitations of the research.

Biocompatibility and resorption pattern of newly developed hyaluronic acid hydrogel reinforced three-layer poly (lactide-co-glycolide) membrane: histologic observation in rabbit calvarial defect model.

Abstract: The aim of this study was to evaluate the biocompatibility and resorption pattern in three-layer poly (lactide-co-glycolide) (PLGA) membrane according to the concentrations of hyaluronic acid (HA) hydrogel in rabbit calvarial defect model. Four standardized circular defects with 8 mm diameter were created on the four rabbit calvarium. Three-layer PLGA membranes (5% and 10% HA gel) were used as the test groups, both collagen membrane and monolayer PLGA membrane as the control groups. After sacrificing the animals after 4 and 8 weeks, block sections were harvested and histological observation was performed. Pus formation was observed in a site on the three-layer PLGA membranes (with 10% HA gel) of 4 weeks group and initial inflammatory responses were observed on the three-layer PLGA membrane group. However, when compared to both the monolayer PLGA membrane group and collagen membrane group, the HA gel-reinforced three-layer PLGA membrane showed improved cell occlusion and retention period, showing the formation of the capsule-like structure. There was no definite difference between the results of the membranes fabricated with either 5% or 10% HA hydrogel. The HA reinforced three-layer PGLA membrane was retained longer than control group and showed good property in cell occlusion. Future study is under process to improve the inflammatory response of the three layer PLGA membranes, which were observed in this study.

Effects of direct current electric-field using ITO plate on breast cancer cell migration.

Abstract: Cell migration is an essential activity of the cells in various biological phenomena. The evidence that electrotaxis plays important roles in many physiological phenomena is accumulating. In electrotaxis, cells move with a directional tendency toward the anode or cathode under direct-current electric fields. Indium tin oxide, commonly referred to as ITO has high luminous transmittance, high infrared reflectance, good electrical conductivity, excellent substrate adherence, hardness and chemical inertness and hence, have been widely and intensively studied for many years. Because of these properties of ITO films, the electrotaxis using ITO plate was evaluated. Under the 0 V/cm condition, MDA-MB-231 migrated randomly in all directions. When 1 V/cm of dc EF was applied, cells moved toward anode. The y forward migration index was -0.046 ± 0.357 under the 0 V/cm and was 0.273 ± 0.231 under direct-current electric field of 1 V/cm. However, the migration speed of breast cancer cell was not affected by direct-current electric field using ITO plate. In this study, we designed a new electrotaxis system using an ITO coated glass and observed the migration of MDA-MB-231 on direct current electric-field of the ITO glass.

Immobilizing hydroxycholesterol with apatite on titanium surfaces to induce ossification

Abstract: Background: Immobilizing bioactive molecules and osteoconductive apatite on titanium implants have investigated direct ossification. In this study, hydroxycholesterol (HC) was immobilized with apatite on titanium through simply adsorption or sandwich-like coating. Three kinds of hydroxycholesterol were chosen to induce ossification: 20α-hydroxycholesterol (20α- HC), 22(S)-hydroxycholesterol (22(S)-HC) and 25-hydroxycholesterol (25-HC).The effects of HC/apatite coating on ossification abilities were evaluated in vitro and in vivo. Results: At 6 d, adsorbed apatite/25-HC and apatite/22(S)-HC coating exhibited some cytotoxicity, while the cell viability of apatite/20α-HC coating was similar as apatite coating. Immobilizing HC with apatite significantly enhanced the ALP activities compared with apatite coating. There was no significant difference in ALP value between adsorbed apatite/HC coating and sandwich-like apatite/HC/apatite coating. When compared with apatite coating, the mineral deposition improved by adsorbed HC with apatite at higher concentration in vivo. Conclusions: When compared with apatite coating, immobilizing HC with apatite coating induced the ossification in vitro and in vivo.