scholarly journals Non-hypertensive tetraPEGylated canine haemoglobin: correlation between PEGylation, O2 affinity and tissue oxygenation

2007 ◽  
Vol 405 (3) ◽  
pp. 503-511 ◽  
Author(s):  
Seetharama A. Acharya ◽  
Vivek N. Acharya ◽  
Nirmala Devi Kanika ◽  
Amy G. Tsai ◽  
Marcos Intaglietta ◽  
...  

TetraPEGylated canine Hb, [SP (succinimidophenyl)-PEG5K]4-canine-Hb, with PEGylation at its four reactive cysteine residues (α111 and β93) has been prepared and characterized. The hydrodynamic volume and the molecular radius of (SP-PEG5K)4-canine-Hb are intermediate to those of di- and hexaPEGylated human Hb as expected. However, the COP (colloidal osmotic pressure) of tetraPEGylated canine Hb is closer to that of hexaPEGylated human Hb than to that of diPEGylated human Hb. The O2 affinity of tetraPEGylated canine Hb is higher than that of canine Hb and comparable with that of hexaPEGylated Hb. The O2 affinity of tetraPEGylated canine Hb is not responsive to the presence of DPG (diphosphoglycerate) or chloride, but it retains almost full response to L-35, an allosteric effector that interacts at the αα-end of the central cavity. The tetraPEGylated canine Hb is vasoinactive in hamster in 10% top load infusion studies. It is also essentially non-hypertensive in an extreme exchange haemodilution protocol in hamster just as di- and hexaPEGylated human Hb. The O2 delivery by tetraPEGylated canine Hb is comparable with that of hexaPEGylated Hb but not as efficient as diPEGylated Hb. These results demonstrate that PEGylation-induced solution properties of PEG [poly(ethylene glycol)]–Hb conjugates are dictated by the level and chemistry of PEGylation and the interplay of these plays a critical role in tissue oxygenation. The studies imply the need to establish the right level (and/or pattern) of PEGylation and O2 affinity of Hb–PEG adducts in designing O2-carrying plasma volume expanders, and this remains the primary challenge in the design of PEGylated Hb as blood substitutes.

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Ming-Hsi Huang ◽  
Yuan-Yi Lu ◽  
Yung-Sheng Lin

In aesthetic medicine, during a course of skin whitening treatment, injections must be frequently administered to achieve a strong curative effect. To develop a method to prevent long-term harm due to injections, this study applied a novel technology for the delivery of whitening agents that achieved long-term slow release of agents, thereby reducing the danger of frequent injections. We utilized biodegradable poly(ethylene glycol)-poly(lactide-co-ε-caprolactone) and Span 85 as surfactants and squalene as the core oil to encapsulate and adsorb tranexamic acid in emulsified particles, respectively. The conductivity test determined that the continuous phase of the obtained emulsified particles was aqueous; tranexamic acid did not play a critical role because of its low content. The controlled release experiment demonstrated that the release rate of tranexamic acid from the emulsified matrix was in the sequence of (1) adsorption, (2) encapsulation plus adsorption, and (3) encapsulation. Encapsulating tranexamic acid can efficiently halt the behavior of sudden release and potentially boost the efficacy of whitening.


2004 ◽  
Vol 382 (1) ◽  
pp. 183-189 ◽  
Author(s):  
Kim D. VANDEGRIFF ◽  
Andrea BELLELLI ◽  
Michele SAMAJA ◽  
Ashok MALAVALLI ◽  
Maurizio BRUNORI ◽  
...  

The hypertensive effect observed with most cell-free haemoglobins has been proposed to result from NO scavenging. However, a newly developed PEG [poly(ethylene glycol)]-conjugated haemoglobin, MalPEG-Hb [maleimide-activated PEG-conjugated haemoglobin], is non-hypertensive with unique physicochemical properties: high O2 affinity, low co-operativity and large molecular radius. It is therefore of interest to compare the ligand-binding properties of MalPEG-Hb with unmodified cell-free HbA (stroma-free human haemoglobin). NO association rates for deoxy and oxyMalPEG-Hb and HbA were found to be identical. These results confirm the lack of correlation between hypertension and NO for a similar modified haemoglobin with high molecular radius and low p50 (pO2 at which haemoglobin is half-saturated with O2) [Rohlfs, Bruner, Chiu, Gonzales, Gonzales, Magde, Magde, Vandegriff and Winslow (1998) J. Biol. Chem. 273, 12128–12134]. The R-state O2 association kinetic constants were also the same for the two haemoglobins. However, even though the p50 of MalPEG-Hb is approx. half of that of HbA, the biphasic O2 dissociation rates measured at relatively high pO2 (150 Torr) were 2-fold higher, giving rise to a 2-fold lower R-state equilibrium association constant for MalPEG-Hb compared with HbA. Thus the O2 affinity of MalPEG-Hb is higher only at pO2 values lower than the intersection point of the O2 equilibrium curves for MalPEG-Hb and HbA. In summary, the present studies found similar rates of NO binding to HbA and MalPEG-Hb, eliminating the possibility that the lack of vasoactivity of MalPEG-Hb is simply the result of reduced molecular reactivity with NO. Alternatively, the unique O2-binding characteristics with low p50 and co-operativity suggest that the ‘R-state’ conformation of MalPEG-Hb is in a more T-state configuration and restricted from conformational change.


MRS Advances ◽  
2016 ◽  
Vol 1 (29) ◽  
pp. 2161-2166
Author(s):  
Mayra Elizabeth García-Sánchez ◽  
Jorge A. Perez-Naitoh ◽  
Daniel E. Ramirez-Arreola ◽  
Jorge R. Robledo-Ortíz ◽  
Pedro Ortega-Gudiño ◽  
...  

ABSTRACTOverall, autologous bone grafting continues to be the gold standard for the restoration of bone defects while other practices include metallic meshes and plates. These practices are not always suitable particularly when performing reconstructive surgery in the maxillofacial region as the defects tend to be complex in terms of size and shape. These bone defect usually occur due to trauma, infection or a result of oncologic surgeries and therefore the patient requires large amount of bone grafting material [1].There is a need for alternative methods such as is artificial bone scaffolds with regenerative medicine approaches in order to enable original tissue regeneration. In order to stimulate tissue regeneration scaffolding materials are required to have certain properties such as biocompatibility, adequate mechanical properties and internal and surface topographical features in order to provide specific biological signals to promote cell attachment and proliferation. Ideally, it would also need to be biodegradable and provide sufficient support for both the particular defect area and cellular ingrowth to degrade over time as new bone tissue is formed [2]. This work analyses the mechanical and chemical properties of Hydroxyapatite (HA) - poly(ethylene glycol) dimethacrylate (PEGDMA) and Hydroxyapatite (HA) - poly(ethylene glycol) diacrylate (PEGDA) based composites used as artificial bone scaffold material with internal structures optimized using finite element analysis (FEA) using Hyperworks OptiStruct (Altair, USA) Topological Optimization and manufactured using commercially available additive manufacturing techniques in order to develop a product that can be introduced directly into the patient. The technique allows implants to be custom made, having the right dimensions and the right mechanical properties.Testing of the ceramic-hydrogel composite include mechanical testing in compression, tension, bending, impact and hardness while chemical analysis include Fourier Transform Infrared spectroscopy (ATR-FTIR) and Differential Scanning Calorimetry (DSC). Morphology was analyzed using Scanning Electron Microscopy (SEM) and Laser Scanning Confocal Microscopy.


2021 ◽  
Vol 12 ◽  
pp. 204173142110212
Author(s):  
Julie E Speer ◽  
Marcos N Barcellona ◽  
Michael Y Lu ◽  
Zizhen Zha ◽  
Liufang Jing ◽  
...  

The nucleus pulposus (NP) of the intervertebral disc plays a critical role in distributing mechanical loads to the axial skeleton. Alterations in NP cells and, consequently, NP matrix are some of the earliest changes in the development of disc degeneration. Previous studies demonstrated a role for laminin-presenting biomaterials in promoting a healthy phenotype for human NP cells from degenerated tissue. Here we investigate the use of laminin-mimetic peptides presented individually or in combination on a poly(ethylene) glycol hydrogel as a platform to modulate the behaviors of degenerative human NP cells. Data confirm that NP cells attach to select laminin-mimetic peptides that results in cell signaling downstream of integrin and syndecan binding. Furthermore, the peptide-functionalized hydrogels demonstrate an ability to promote cell behaviors that mimic that of full-length laminins. These results identify a set of peptides that can be used to regulate NP cell behaviors toward a regenerative engineering strategy.


2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Anton Bonartsev ◽  
Vera Voinova ◽  
Elizaveta Akoulina ◽  
Andrey Dudun ◽  
Irina Zharkova ◽  
...  

2007 ◽  
Vol 32 (5) ◽  
pp. 431-446 ◽  
Author(s):  
Tahar Bartil ◽  
Mahmoud Bounekhel ◽  
Cedric Calberg ◽  
Robert Jerome

2019 ◽  
Author(s):  
Alex Khang ◽  
Andrea Gonzalez Rodriguez ◽  
Megan E. Schroeder ◽  
Jacob Sansom ◽  
Emma Lejeune ◽  
...  

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