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.
J. Funct. Biomater.2014, 5(3), 197-210; doi:10.3390/jfb5030197 - published 18 September 2014 Show/Hide Abstract
Abstract: Osteoarthritis is a painful degenerative joint disease that could be better managed if tissue engineers can develop methods to create long-term engineered articular cartilage tissue substitutes. Many of the tissue engineered cartilage constructs currently available lack the chemical stimuli and cell-friendly environment that promote the matrix accumulation and cell proliferation needed for use in joint cartilage repair. The goal of this research was to test the efficacy of using a fibrin-alginate hydrogel containing hyaluronic acid (HA) and/or chondroitin sulphate (CS) supplements for chondrocyte culture. Neonatal porcine chondrocytes cultured in fibrin-alginate hydrogels retained their phenotype better than chondrocytes cultured in monolayer, as evidenced by analysis of their relative expression of type II versus type I collagen mRNA transcripts. HA or CS supplementation of the hydrogels increased matrix glycosaminoglycan (GAG) production during the first week of culture. However, the effects of these supplements on matrix accumulation were not additive and were no longer observed after two weeks of culture. Supplementation of the hydrogels with CS or a combination of both CS and HA increased the chondrocyte cell population after two weeks of culture. Statistical analysis indicated that the HA and CS treatment effects on chondrocyte numbers may be additive. This research suggests that supplementation with CS and/or HA has positive effects on cartilage matrix production and chondrocyte proliferation in three-dimensional (3D) fibrin-alginate hydrogels.
J. Funct. Biomater.2014, 5(3), 183-196; doi:10.3390/jfb5030183 - published 17 September 2014 Show/Hide Abstract
Abstract: IPNs are unique “alloys” of cross-linked polymers in which at least one network is synthesized and/or cross-linked in the presence of the other. IPNs are also known as entanglements of polymer networks that are ideally held together only by permanent topological interactions. The objectives of this study are to evaluate novel chitosan-based functional drug delivery systems that can be successfully incorporated into “dual action bioactive tooth restorative materials”. These materials should be capable of inducing an improved wound healing prototype. The novel hydrogels will be investigated with respect to the antioxidant capacity of conventional antioxidants, such as resveratrol, b-carotene and propolis, as a designer drug delivery system, with the use of SEM imaging for the characterization of the surfaces, bio-adhesive property, antioxidant capacity, free radical defence, antioxidant, active ingredient stability and reactive features of novel materials. The additional benefit of the site-specific “functional restorative material” for use in dressings to deliver antibiotics to wound sites can provide tissue compatibility and reduced interference with wound healing. The materials were tested using an effective in vitro free radical generation model as functional additive prototypes for further development of “dual function restorative wound healing materials”. We quantified the effects of functional designer biomaterials on the dentin bond strength of a composite and evaluated the bio-adhesive capacity of the materials in the two separate “in vitro” systems. The added benefits of the chitosan/vitamin C/cyclodextrin (CD) host:guest complex-treated hydrogels involved a positive influence on the tetracycline release, increased dentin bond strength, as well as a demonstrated in vitro “built-in” free radical defence mechanism and, therefore, acting as a “proof of concept” for functional multi-dimensional restorative wound healing materials with a built-in free radical defence mechanism.Based on our results, we can conclude that the CD:chitosan-antioxidant-containing hydrogels are a suitable carrier for tetracycline to be slow-released. Within the limitations of the study design, chitosan-based hydrogels are suitable materials for functional restorative and wound healing applications in vitro. Cytotoxicity data are currently being evaluated in our laboratory.
J. Funct. Biomater.2014, 5(3), 167-182; doi:10.3390/jfb5030167 - published 16 September 2014 Show/Hide Abstract
Abstract: Short interfering RNA (siRNA) targeted against anti-apoptotic Bcl-2 protein proved to knockdown its expression and trigger cancer cell death. We used degradable, pH-sensitive, comb-like [P(EAA-co-BMA)-b-PNASI-g-P(HMA-co-TMAEMA)] polymer to condense anti-Bcl-2 siRNA into “smart” particles, which proved to shuttle their cargo past the endosomal membrane and into the cytoplasm of HeLa and UM-SCC-17B cancer cells. HeLa and UM-SCC-17B cancer cells were treated with anti-Bcl-2 particles followed by quantifying Bcl-2 mRNA and protein levels using qRT-PCR and western blotting, respectively. “Smart” anti-Bcl-2 particles selectively suppress Bcl-2 mRNA and protein levels in HeLa cells by 50%–60% and 79%–81%, respectively. Similarly, “smart” anti-Bcl-2 particles inhibited Bcl-2 mRNA levels by 30%, 40%, and 20% upon incubation with UM-SCC-17B cancer cells for 48, 72, and 96 h, respectively. Bcl-2 protein expression in UM-SCC-17B cancer cells was inhibited by 30% after treatment for 72 h. Results show that pH-sensitive comb-like polymer complex anti-Bcl-2 siRNA forming “smart” nanoparticles that deliver their cargo into the cytoplasm of HeLa and UM-SCC-17B cancer cells causing Bcl-2 knockdown at the mRNA and protein levels.