J. Funct. Biomater.2014, 5(4), 288-295; doi:10.3390/jfb5040288 - published 12 December 2014 Show/Hide Abstract
Abstract: For many decades, Hemoglobin-based oxygen carriers (HBOCs) have been central in the development of resuscitation agents that might provide oxygen delivery in addition to simple volume expansion. Since 80% of the world population lives in areas where fresh blood products are not available, the application of these new solutions may prove to be highly beneficial (Kim and Greenburg 2006). Many improvements have been made to earlier generation HBOCs, but various concerns still remain, including coagulopathy, nitric oxide scavenging, platelet interference and decreased calcium concentration secondary to volume expansion (Jahr et al. 2013). This review will summarize the current challenges faced in developing HBOCs that may be used clinically, in order to guide future research efforts in the field.
J. Funct. Biomater.2014, 5(4), 273-287; doi:10.3390/jfb5040273 - published 28 November 2014 Show/Hide Abstract
Abstract: Greige cotton contains waxes and pectin on the outer surface of the fiber that are removed when bleached, but these components present potential wound dressing functionality. Cotton nonwovens blended with hydrophobic and hydrophilic fibers including viscose, polyester, and polypropylene were assessed for clotting activity with thromboelastography (TEG) and thrombin production. Clotting was evaluated based on TEG measurements: R (time to initiation of clot formation), K (time from end of R to a 20 mm clot), α (rate of clot formation according to the angle tangent to the curve as K is reached), and MA (clot strength). TEG values correlate to material surface polarity as measured with electrokinetic parameters (ζplateau, Δζ and swell ratio). The material surface polarity (ζplateau) varied from −22 to −61 mV. K values and thrombin concentrations were found to be inversely proportional to ζplateauwith an increase in material hydrophobicity. An increase in the swell ratios of the materials correlated with decreased K values suggesting that clotting rates following fibrin formation increase with increasing material surface area due to swelling. Clot strength (MA) also increased with material hydrophobicity. Structure/function implications from the observed clotting physiology induced by the materials are discussed.
J. Funct. Biomater.2014, 5(4), 259-272; doi:10.3390/jfb5040259 - published 28 November 2014 Show/Hide Abstract
Abstract: Healing is a speciﬁc biological process related to the general phenomenon of growth and tissue regeneration and is a process generally affected by several systemic conditions or as detrimental side-effects of chemotherapy- and radiotherapy-induced inflammation of the oral mucosa. The objectives of this study is to evaluate the novel chitosan based functional drug delivery systems, which can be successfully incorporated into “dual action bioactive restorative materials”, capable of inducing in vitro improved wound healing prototype and containing an antibiotic, such as nystatin, krill oil as an antioxidant and hydroxyapatite as a molecular bone scaffold, which is naturally present in bone and is reported to be successfully used in promoting bone integration when implanted as well as promoting healing. The hydrogels were prepared using a protocol as previously reported by us. The physico-chemical features, including surface morphology (SEM), release behaviors, stability of the therapeutic agent-antioxidant-chitosan, were measured and compared to the earlier reported chitosan-antioxidant containing hydrogels. Structural investigations of the reactive surface of the hydrogel are reported. Release of nystatin was investigated for all newly prepared hydrogels. Bio-adhesive studies were performed in order to assess the suitability of these designer materials. Free radical defense capacity of the biomaterials was evaluated using established in vitro model. The bio-adhesive capacity of the materials in the in vitro system was tested and quantified. It was found that the favorable synergistic effect of free radical built-in defense mechanism of the new functional materials increased sustainable bio-adhesion and therefore acted as a functional multi-dimensional restorative material with potential application in wound healing in vitro.
J. Funct. Biomater.2014, 5(4), 246-258; doi:10.3390/jfb5040246 - published 18 November 2014 Show/Hide Abstract
Abstract: The use of hemoglobin-based oxygen carriers (HBOC) as oxygen delivering therapies during hypoxic states has been hindered by vasoconstrictive side effects caused by depletion of nitric oxide (NO). OxyVita C is a promising oxygen-carrying solution that consists of a zero-linked hemoglobin polymer with a high molecular weight (~17 MDa). The large molecular weight is believed to prevent extravasation and limit NO scavenging and vasoconstriction. The aim of this study was to assess vasoactive effects of OxyVita C on systemic blood pressures and cerebral pial arteriole diameters. Anesthetized healthy rats received four intravenous (IV) infusions of an increasing dose of OxyVita C (2, 25, 50, 100 mg/kg) and hemodynamic parameters and pial arteriolar diameters were measured pre- and post-infusion. Normal saline was used as a volume-matched control. Systemic blood pressures increased (P ≤ 0.05) with increasing doses of OxyVita C, but not with saline. There was no vasoconstriction in small (<50 µm) and medium-sized (50–100 µm) pial arterioles in the OxyVita C group. In contrast, small and medium-sized pial arterioles vasoconstricted in the control group. Compared to saline, OxyVita C showed no cerebral vasoconstriction after any of the four doses evaluated in this rat model despite increases in blood pressure.
J. Funct. Biomater.2014, 5(4), 232-245; doi:10.3390/jfb5040232 - published 27 October 2014 Show/Hide Abstract
Abstract: At least a third of the blood supply in the world is used to transfuse 1–2 units of packed red blood cells for each intervention and most clinical trials of blood substitutes have been carried out at this level of oxygen carrying capacity (OCC) restoration. However, the increase of oxygenation achieved is marginal or none at all for molecular hemoglobin (Hb) products, due to their lingering vasoactivity. This has provided the impetus for the development of “oxygen therapeutics” using Hb-based molecules that have high oxygen affinity and target delivery of oxygen to anoxic areas. However it is still unclear how these oxygen carriers counteract or mitigate the functional effects of anemia due to obstruction, vasoconstriction and under-perfusion. Indeed, they are administered as a low dosage/low volume therapeutic Hb (subsequently further diluted in the circulatory pool) and hence induce extremely small OCC changes. Hyperviscous plasma expanders provide an alternative to oxygen therapeutics by increasing the oxygen delivery capacity (ODC); in anemia they induce supra-perfusion and increase tissue perfusion (flow) by as much as 50%. Polyethylene glycol conjugate albumin (PEG-Alb) accomplishes this by enhancing the shear thinning behavior of diluted blood, which increases microvascular endothelial shear stress, causes vasodilation and lowering peripheral vascular resistance thus facilitating cardiac function. Induction of supra-perfusion takes advantage of the fact that ODC is the product of OCC and blood flow and hence can be maintained by increasing either or both. Animal studies suggest that this approach may save a considerable fraction of the blood supply. It has an additional benefit of enhancing tissue clearance of toxic metabolites.
J. Funct. Biomater.2014, 5(4), 211-231; doi:10.3390/jfb5040211 - published 24 October 2014 Show/Hide Abstract
Abstract: In this paper, we discuss the synthesis and self-assembling behavior of new copolymers derived from fatty acid/amino acid components, namely dimers of linoleic acid (DLA) and tyrosine derived diphenols containing alkyl ester pendent chains, designated as “R” (DTR). Specific pendent chains were ethyl (E) and hexyl (H). These poly(aliphatic/aromatic-ester-amide)s were further reacted with poly(ethylene glycol) (PEG) and poly(ethylene glycol methyl ether) of different molecular masses, thus resulting in ABA type (hydrophilic-hydrophobic-hydrophilic) triblock copolymers. We used Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopies to evaluate the chemical structure of the final materials. The molecular masses were estimated by gel permeation chromatography (GPC) measurements. The self-organization of these new polymeric systems into micellar/nanospheric structures in aqueous environment was evaluated using ultraviolet/visible (UV-VIS) spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM). The polymers were found to spontaneously self-assemble into nanoparticles with sizes in the range 196–239 nm and critical micelle concentration (CMC) of 0.125–0.250 mg/mL. The results are quite promising and these materials are capable of self-organizing into well-defined micelles/nanospheres encapsulating bioactive molecules, e.g., vitamins or antibacterial peptides for antibacterial coatings on medical devices.