Characteristics of Poly-l-Ornithine-coated alginate microcapsules

Darrabie, Marcus D.; Kendall, William F.; Opara, Emmanuel C.

doi:10.1016/j.biomaterials.2005.05.009

Cited by 136 publications

(95 citation statements)

References 28 publications

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“…In comparison, the PLO coated microcapsules gave significantly less TCC. The use of PLO instead of PLL is shown to increase the stability of alginatepolycation microcapsules [23][24][25]. PLO differs from PLL by containing three methyl groups instead of four in the pendant moiety, which is responsible for more stable complexes with a negatively charged biopolymer as DNA [26].…”

Section: Cd11b Cd18 or Cd11c Blockagementioning

confidence: 99%

Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation

Ørning

Hoem

Coron

et al. 2016

Journal of Controlled Release

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The inflammatory potential of 12 types of alginate-based microspheres was assessed in a human whole blood model. The inflammatory potential could be categorized from low to high based on the four main alginate microsphere types; alginate microbeads, liquefied core poly-L-ornithine (PLO)-containing microcapsules, liquefied core poly-L-lysine (PLL)-containing microcapsules, and solid core PLLcontaining microcapsules. No complement or inflammatory cytokine activation was detected for the Ca/Ba alginate microbeads. Liquefied core PLO-and PLL-containing microcapsules induced significant fluid phase complement activation (TCC), but with low complement surface deposition (anti-C3c), and a low proinflammatory cytokine secretion, with exception of an elevated MCP-1(CCL2) secretion. The solid core PLL-containing microcapsules generated lower TCC but a marked complement surface deposition and significant induction of the proinflammatory cytokines interleukin (IL-1)β, TNF, IL-6, the chemokines IL-8 (CXCL8), and MIP-1α (CCL3) and MCP-1(CCL2).Inhibition with compstatin (C3 inhibitor) completely abolished complement surface deposition, leukocyte adhesion and the proinflammatory cytokines. The C5 inhibitions partly lead to a reduction of the proinflammatory cytokines. The leukocyte adhesion was abolished by inhibitory antibodies against CD18 and partly reduced by CD11b, but not by CD11c. Anti-CD18 significantly reduced the (IL-1)β, TNF, IL-6 and MIP-1α and anti-CD11b significantly reduced the IL-6 and VEGF secretion. MCP-1 was strongly activated by anti-CD18 and anti-CD11b. In conclusion the initial proinflammatory cytokine responses are driven by the microspheres potential to trigger complement C3 (C3b/iC3b) deposition, leukocyte activation and binding through complement receptor CR3 (CD11b/CD18).MCP-1 is one exception dependent on the fluid phase complement activation mediated through CR3.

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Section: Cd11b Cd18 or Cd11c Blockagementioning

confidence: 99%

Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation

Ørning

Hoem

Coron

et al. 2016

Journal of Controlled Release

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“…Isolated islets can be encapsulated within permeable hydrogels such as alginate to provide an immunoprotective barrier that may preclude pharmacological immunosuppression. 8,9 However, encapsulation devices introduce a transport barrier between the host and graft tissues and inherently limit oxygen supply, compromising graft function and cell viability, 10 problems that scale with device wall thickness. 11,12 Typically grafts are implanted in subcutaneous 13 or intraperitoneal 14 sites where partial pressures of oxygen (pO 2 ) are approximately 60 and 40 mm Hg, respectively, which is lower than that of arterial blood (>80 mm Hg).…”

Section: Introductionmentioning

confidence: 99%

Method measuring oxygen tension and transport within subcutaneous devices

et al. 2014

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Abstract. Cellular therapies hold promise to replace the implantation of whole organs in the treatment of disease. For most cell types, in vivo viability depends on oxygen delivery to avoid the toxic effects of hypoxia. A promising approach is the in situ vascularization of implantable devices which can mediate hypoxia and improve both the lifetime and utility of implanted cells and tissues. Although mathematical models and bulk measurements of oxygenation in surrounding tissue have been used to estimate oxygenation within devices, such estimates are insufficient in determining if supplied oxygen is sufficient for the entire thickness of the implanted cells and tissues. We have developed a technique in which oxygen-sensitive microparticles (OSMs) are incorporated into the volume of subcutaneously implantable devices. Oxygen partial pressure within these devices can be measured directly in vivo by an optical probe placed on the skin surface. As validation, OSMs have been incorporated into alginate beads, commonly used as immunoisolation devices to encapsulate pancreatic islet cells. Alginate beads were implanted into the subcutaneous space of Sprague-Dawley rats. Oxygen transport through beads was characterized from dynamic OSM signals in response to changes in inhaled oxygen. Changes in oxygen dynamics over days demonstrate the utility of our technology. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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“…Usually this is associated with a slight increase in empty capsules but minimizing protruding islets is of upmost priority. In many cases, the inner alginate bead will be either completely or partially liquefied by the removal of calcium ions with calcium quenching reagents such as sodium citrate, which allows for improved diffusion in the microbeads (Darrabie et al, 2005). Another consideration is the morphology of the microcapsules used for encapsulated islets.…”

Section: Microencapsulationmentioning

confidence: 99%

“…Unlike PLL, PLO has been shown to evoke less of an immune response and has been shown to have improved mechanical properties (Brunetti et al, 1991;Calafiore et al, 1997;Calafiore et al, 2004;Kizilel et al, 2005). When compared to alginate-PLL microcapsules, alginate-PLO microcapsules have been shown to better resist swelling and bursting under osmotic stress (Darrabie et al, 2005). Bead swelling is an important factor to take into consideration because it can lead to increased in pore size, permeability, and shear stress, which leads to decreased islet viability (Thu et al, 1996a).…”

Section: Poly-l-ornithine (Plo)mentioning

confidence: 99%

“…Bead swelling is an important factor to take into consideration because it can lead to increased in pore size, permeability, and shear stress, which leads to decreased islet viability (Thu et al, 1996a). It has been hypothesized that the improved mechanical properties of alginate-PLO microcapsules over alginate-PLL microcapsules is due to the improved bonding of PLO to alginate owing to the shorter monomer structure of PLO (Darrabie et al, 2005;Inaki et al, 1997). Also, while PLL seems to bind to M-G sequences, PLO has been shown to prefer M-M sequences (Calafiore et al, 2006).…”

Section: Poly-l-ornithine (Plo)mentioning

confidence: 99%

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