Peroxide-based oxygen generating topical wound dressing for enhancing healing of dermal wounds.

Oxygen generating biomaterials represent a new trend in regenerative medicine that aims to generate and supply oxygen at the site of requirement, to support tissue healing and regeneration. To enhance the healing of dermal wounds, we have developed a highly portable, in situ oxygen generating wound dressings that uses sodium percarbonate (SPO) and calcium peroxide (CPO) as chemical oxygen sources. The dressing continuously generated oxygen for more than 3 days, after which it was replaced. In the in vivo testing on porcine full-thickness porcine wound model, the SPO/CPO dressing showed enhanced wound healing during the 8 week study period. Quantitative measurements of wound healing related parameters, such as wound closure, reepithelialization, epidermal thickness and collagen content of dermis showed that supplying oxygen topically using the SPO/CPO dressing significantly accelerated the wound healing. An increase in neovascularization, as determined using Von Willebrand factor (vWF) and CD31 staining, was also observed in the presence of SPO/CPO dressing. This novel design for a wound dressing that contains oxygen generating biomaterials (SPO/CPO) for supplying topical oxygen, may find utility in treating various types of acute to chronic wounds.

Gene-environment interaction in molar-incisor hypomineralization.

Molar incisor hypomineralization (MIH) is an enamel condition characterized by lesions ranging in color from white to brown which present rapid caries progression, and mainly affects permanent first molars and incisors. These enamel defects usually occur when there are disturbances during the mineralization or maturation stage of amelogenesis. Both genetic and environmental factors have been suggested to play roles in MIH's development, but no conclusive risk factors have shown the source of the disease. During head and neck development, the interferon regulatory factor 6 (IRF6) gene is involved in the structure formation of the oral and maxillofacial regions, and the transforming growth factor alpha (TGFA) is an essential cell regulator, acting during proliferation, differentiation, migration and apoptosis. In this present study, it was hypothesized that these genes interact and contribute to predisposition of MIH. Environmental factors affecting children that were 3 years of age or older were also hypothesized to play a role in the disease etiology. Those factors included respiratory issues, malnutrition, food intolerance, infection of any sort and medication intake. A total of 1,065 salivary samples from four different cohorts were obtained, and DNA was extracted from each sample and genotyped for nine different single nucleotide polymorphisms. Association tests and logistic regression implemented in PLINK were used for analyses. A potential interaction between TGFA rs930655 with all markers tested in the cohort from Turkey was identified. These interactions were not identified in the remaining cohorts. Associations (p<0.05) between the use of medication after three years of age and MIH were also found, suggesting that conditions acquired at the age children start to socialize might contribute to the development of MIH.

Phenome-Wide Scan Finds Potential Orofacial Risk Markers for Cancer.

Cancer is a disease caused by a process that drives the transformation of normal cells into malignant cells. The late diagnosis of cancer has a negative impact on the health care system due to high treatment cost and decreased chances of favorable prognosis. Here, we aimed to identify orofacial conditions that can serve as potential risk markers for cancers by performing a phenome-wide scan (PheWAS). From a pool of 6,100 individuals, both genetic and epidemiological data of 1,671 individuals were selected: 350 because they were previously diagnosed with cancer and 1,321 to match to those individuals that had cancer, based on age, sex, and ethnicity serving as a comparison group. Results of this study showed that when analyzing the individuals affected by cancer separately, tooth loss/edentulism is associated with SNPs in AXIN2 (rs11867417 p = 0.02 and rs2240308 p = 0.02), and leukoplakia of oral mucosa is associated with both AXIN2 (rs2240308 p = 0.03) and RHEB (rs2374261 p = 0.03). These phenotypes did not show the same trends in patients that were not diagnosed with cancer, allowing for the conclusion that these phenotypes are unique to cases with higher cancer risk.

Carbon nanotube applications for tissue engineering.

As the field of tissue engineering advances, new tools for better monitoring and evaluating of engineered tissues along with new biomaterials to direct tissue growth are needed. Carbon nanotubes may be an important tissue engineering material for improved tracking of cells, sensing of microenvironments, delivering of transfection agents, and scaffolding for incorporating with the host's body. Using carbon nanotubes for optical, magnetic resonance and radiotracer contrast agents would provide better means of evaluating tissue formation. In addition, monitoring and altering intra and intercellular processes would be useful for design of better engineered tissues. Carbon nanotubes can also be incorporated into scaffolds providing structural reinforcement as well as imparting novel properties such as electrical conductivity into the scaffolds may aid in directing cell growth. Potential cytotoxic effects associated with carbon nanotubes may be mitigated by chemically functionalizing the surface. Overall, carbon nanotubes may play an integral role as unique biomaterial for creating and monitoring engineered tissue.

Oxygen producing biomaterials for tissue regeneration.

A limiting factor in regenerating large organs and healing large wounds completely is the inability to provide oxygen to the affected areas for vascularization and healing to occur. An oxygen rich compound of sodium percarbonate was incorporated into films of Poly(D,L-lactide-co-glycolide) (PLGA) and used for in situ production of oxygen. Oxygen release could be observed from the film over a period of 24 h. When the oxygen producing biomaterials were placed in contact with ischemic tissue in a mouse model, decreased tissue necrosis and cellular apoptosis was observed. This indicates that improved tissue viability could be maintained for several days using oxygen producing biomaterials.

Carbon nanotube--poly(3-octylthiophene) composite photovoltaic cells.

The effects of varying nanotube loading/concentration in carbon nanotube-poly(3-octylthiophene) blends used as thin film photovoltaic cells, have been studied. The network of single walled nanotubes clearly aids in exciton separation and modifies carrier mobility within the active layer as suggested by a bulk heterojunction model. Further, modifications to the metal-polymer interface occur with the addition of nanotubes leading to variations in the observed VOC of the photovoltaic cells. Finally, the "nanocomposite" devices exhibit significant enhancements to external power conversion efficiencies, with the overall efficiency strongly dependent on device design parameters such as the addition of buffer layers.

Oxygen-Generating Biomaterials: A New, Viable Paradigm for Tissue Engineering?

There have been many attempts to provide sufficient nutrients, especially oxygen, to engineered large tissues to overcome the effects of hypoxia or poor vascularization. Delivering sufficient oxygen to the transplanted cells is one of the most critical issues that affects cell survival and correct maturation of engineered tissues. An emerging approach is using 3D scaffolds made from oxygen-generating biomaterials to tackle transport limitations deep within the engineered tissues. This class of biomaterials has opened a new window for overcoming the challenges associated with ischemia occurring within large tissue constructs. This review critically assesses oxygen-generating reagents, the main approaches for developing oxygen-generating biomaterials, and their potential as 3D scaffolds for regenerative medicine in a clinical setting.

Morphology impact on oxygen sensing ability of Ru(dpp)3Cl2 containing biocompatible polymers.

Especially for tissue engineering applications, the diffusion of oxygen is a critical factor affecting spatial distribution and migration of cells. The cellular oxygen demand also fluctuates depending on tissue type and growth phase. Sensors that determine dissolved oxygen levels under biological conditions provide critical metabolic information about the growing cells as well as the state of the tissue culture within the tissue scaffold. This work focused on the effect of the scaffold morphology on the oxygen sensing response time. It was found that electrospun scaffolds had a faster oxygen-sensing response time than their bulk film counterparts. Tris-(4,7-diphenyl-1,10-phenanthroline) ruthenium (II) dichloride doped electrospun fiber mats of polycaprolactone (PCL) were found to be the most responsive to the presence of oxygen, followed by polyethylene (PEO) glycol mats. Systems containing poly vinyl alcohol were found to be the least responsive. This would suggest that, out of all the polymers tested, PCL and PEO are the most suitable biomaterials for oxygen-sensing applications.

Magnetically stimulated ciprofloxacin release from polymeric microspheres entrapping iron oxide nanoparticles.

To extend the external control capability of drug release, iron oxide nanoparticles (NPs) encapsulated into polymeric microspheres were used as magnetic media to stimulate drug release using an alternating magnetic field. Chemically synthesized iron oxide NPs, maghemite or hematite, and the antibiotic ciprofloxacin were encapsulated together within polycaprolactone microspheres. The polycaprolactone microspheres entrapping ciprofloxacin and magnetic NPs could be triggered for immediate drug release by magnetic stimulation at a maximum value of 40%. Moreover, the microspheres were cytocompatible with fibroblasts in vitro with a cell viability percentage of more than 100% relative to a nontreated control after 24 hours of culture. Macrophage cell cultures showed no signs of increased inflammatory responses after in vitro incubation for 56 hours. Treatment of Staphylococcus aureus with the magnetic microspheres under an alternating (isolating) magnetic field increased bacterial inhibition further after 2 days and 5 days in a broth inhibition assay. The findings of the present study indicate that iron oxide NPs, maghemite and hematite, can be used as media for stimulation by an external magnetic energy to activate immediate drug release.

Skeletal myotube formation enhanced by electrospun polyurethane carbon nanotube scaffolds.

BACKGROUND: This study examined the effects of electrically conductive materials made from electrospun single- or multiwalled carbon nanotubes with polyurethane to promote myoblast differentiation into myotubes in the presence and absence of electrical stimulation. METHODS AND RESULTS: After electrical stimulation, the number of multinucleated myotubes on the electrospun polyurethane carbon nanotube scaffolds was significantly larger than that on nonconductive electrospun polyurethane scaffolds (5% and 10% w/v polyurethane). In the absence of electrical stimulation, myoblasts also differentiated on the electrospun polyurethane carbon nanotube scaffolds, as evidenced by expression of Myf-5 and myosin heavy chains. The myotube number and length were significantly greater on the electrospun carbon nanotubes with 10% w/v polyurethane than on those with 5% w/v polyurethane. The results suggest that, in the absence of electrical stimulation, skeletal myotube formation is dependent on the morphology of the electrospun scaffolds, while with electrical stimulation it is dependent on the electrical conductivity of the scaffolds. CONCLUSION: This study indicates that electrospun polyurethane carbon nanotubes can be used to modulate skeletal myotube formation with or without application of electrical stimulation.

A chemically polymerized electrically conducting composite of polypyrrole nanoparticles and polyurethane for tissue engineering.

A variety of cell types respond to electrical stimuli; accordingly, many conducting polymers (CPs) have been used as tissue engineering (TE) scaffolds, and one such CP is polypyrrole (PPy). PPy is a well-studied biomaterial with potential TE applications because of its electrical conductivity and many other beneficial properties. Combining its characteristics with an elastomeric material, such as polyurethane (PU), may yield a hybrid scaffold with electrical activity and significant mechanical resilience. Pyrrole was in situ polymerized within a PU emulsion mixture in weight ratios of 1:100, 1:20, 1:10, and 1:5, respectively. Morphology, electrical conductivity, mechanical properties, and cytocompatibility with C2C12 myoblast cells were characterized. The polymerization resulted in a composite with a principle base of PU interspersed with an electrically percolating network of PPy nanoparticles. As the mass ratio of PPy to PU increased so did electrical conductivity of the composites. In addition, as the mass ratio of PPy to PU increased, stiffness of the composite increased while maximum elongation length decreased. Ultimate tensile strength was reduced by ~47% across all samples with the addition of PPy to the PU base. Cytocompatibility assay data indicated no significant cytotoxic effect from the composites. Static cellular seeding of C2C12 cells and subsequent differentiation showed myotube formation on the composite materials.

Oxygen generating scaffolds for enhancing engineered tissue survival.

One of the continued challenges in engineering clinically applicable tissues is the establishment of vascularization upon implantation in vivo. Although the effectiveness of an enhanced angiogenic response using various growth factors has been demonstrated in many tissue systems, the rate of angiogenesis could not be accelerated. In this study we investigated whether incorporating oxygen generating biomaterials into tissue engineered constructs would provide a sustained oxygen release over an extended period of time. We examined whether oxygen generating biomaterials are able to maintain cell viability while also maintaining structural integrity of a 3-D construct. Calcium peroxide-based oxygen generating particles were incorporated into 3-D scaffolds of Poly(d,l-lactide-co-glycolide) (PLGA). The scaffolds were designed to generate oxygen over the course of 10 days and simultaneously maintain sufficient mechanical integrity. Scaffolds containing oxygen generating materials maintained elevated levels of oxygen when incubated under hypoxic conditions. Further, these biomaterials were able to extend cell viability growth under hypoxic conditions. These findings indicate that the use of oxygen generating biomaterials may allow for increased cell survivability while neovascularization is being established after implantation. Such scaffolds may play an important role in tissue engineering where currently oxygen diffusion limits the engineering of large tissue implants.

In vitro and in vivo characterization of a novel liposomal butorphanol formulation for treatment of pruritus.

As yet no transdermal topical formulations have been developed for the treatment of chronic itch. We developed a formulation containing 2 mg butorphanol tartrate in 100 microl purified water encapsulated into multilamellar phospholipid vesicles. Drug permeation experiments were studied with Franz diffusion chambers using human skin in vitro and on rat skin in vivo. Histological analysis of rat skins was performed to evaluate skin irritation of the formulation in vivo. Physical properties showed stable formulation with desirable viscosity. In vitro dermal penetration rate data suggest that there was significant permeation at time-points 2 h and 4 h, and a steady state was achieved afterwards to 24 h. Maximal plasma butorphanol concentration was noted at 2 h and steady state was achieved at 8 h. Visual skin assessment as well as histological analysis of excised rat skin did not demonstrate any evidence of inflammation and irritation. In vitro and in vivo analysis demonstrated release of a consistent amount of butorphanol in a sustained manner for 24 h. This liposomal transdermal delivery formulation could serve as a method to deliver butorphanol for patients with chronic pruritus.