Reduction of adhesion formation by postoperative administration of ionically cross-linked hyaluronic acid

Johns, Douglas B.; Rodgers, Kathleen E.; Donahue, William D.; Kiorpes, Timothy C.; diZerega, Gere S.

doi:10.1016/s0015-0282(97)81472-0

Cited by 89 publications

(51 citation statements)

References 5 publications

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“…A number of membranous barrier devices have been developed commercially, with varying degrees of success [1]. Gels that form in situ by simple mixing of two different polymers are appealing for this purpose as they are easy to handle at room temperature and do not require a radiant light source or toxic chemical cross-linkers [2][3][4][5][6][7][8]. They are generally easier to apply over the injured areas, especially if those are difficult to cover with simple sheets, or if the area is very large.…”

Section: Introductionmentioning

confidence: 99%

“…Hyaluronic acid (HA) is a good candidate material for such an application [2][3][4][6][7][8], because HA is well-known to be biocompatible in the peritoneum [1], and chemically cross-linked HA hydrogels (HAX) can prevent peritoneal adhesions in a rabbit model [6]. Hyaluronic acid is degraded by endogenous hyaluronidase [9] and by hydroxyl radicals [10,11].…”

Section: Introductionmentioning

confidence: 99%

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The prevention of peritoneal adhesions by in situ cross-linking hydrogels of hyaluronic acid and cellulose derivatives

et al. 2007

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Postoperative peritoneal adhesions can cause pelvic pain, infertility, and potentially lethal bowel obstruction. We have designed and synthesized injectable hydrogels that are formed by mixing hydrazide-modified hyaluronic acid (HA) with aldehyde-modified versions of cellulose derivatives such as carboxymethylcellulose (CMC), hydroxypropylmethyl cellulose (HPMC), and methyl cellulose (MC). Gelation of these hydrogels occurred in less than 1 min, and had higher shear moduli than that of HA-HA gel (HAX). Hydrogels degraded in the presence of hyaluronidase in vitro, with HA-MC and HA-HPMC degrading more slowly than HAX and HA-CMC. The aldehyde-modified cellulose derivatives showed dose-dependent mild-to-moderate cytotoxicity to mesothelial cells and macrophages in vitro, but all were biocompatible in the murine peritoneum, causing no adhesions for 3 weeks. All the cellulose-derived gels showed efficacy in reducing the area of adhesion formation in a rabbit sidewall defect-bowel abrasion model.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The prevention of peritoneal adhesions by in situ cross-linking hydrogels of hyaluronic acid and cellulose derivatives

et al. 2007

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“…Iron is involved in many complex biological processes, not only in oxidation-reduction catalysis and bioenergetics, but also in many acid-base reactions [12][13][14][15] and when complexed to biopolymers it affects their properties described above.…”

Section: Introductionmentioning

confidence: 99%

Fe (III) - Galactomannan Solid and Aqueous Complexes: Potentiometric, EPR Spectroscopy and Thermal Data

Mercê¹,

Fernandes²,

Mangrich³

et al. 2001

J. Braz. Chem. Soc.

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Galactomananas podem ser empregadas como aditivos na indústria alimentícea para modificar a viscosidade do produto final. Como não são absorvidas pelo organismo humano, sua adição a alimentos dietéticos é muito promissora. Os equilíbrios entre Fe(III) e galactomananas e arabinogalactana de várias leguminosas foram caracterizadas por titulações potenciométricas e espectroscopia de EPR. Os logaritmos das constantes de equilíbrio para a formação dos complexos ML (M = Fe(III) e L = unidade monomérica dos biopolímeros) foram iguais a 15,4, 14,1 e 18,5 para as galactomananas de C. fastuosa, L. leucocephala e S. macranthera, respectivamente. Os valores de log K para a formação das espécies protonadas (MHL) foram 3,1, 3,3 para as galactomananas de C. fastuosa, L. leucocephala e não foi detectado no caso da galactomanana de S. macranthera. Os valores de log de K para a formação de ML 2 foram 14,1, 13,3 e 15,2, respectivamente. Não foi possível obter dados relativos ao equilíbrio entre arabinogalactana e Fe(III) devido à formação de produtos insolúveis logo no início das titulações. Os ensaios no estado sólido mostraram não somente uma grande interação dipolar entre dois íons Fe(III) na estrutura polimérica complexada, tanto maior quanto menos substituída é a galactomanana, mas também a estabilidade térmica resultante desta complexação. Os produtos complexados podem conferir uma abrangência maior na utilização em produtos dietéticos, pois a presença de um metal essencial no complexo, quando de sua descomplexação nos vários processos fisiológicos dos organismos, faculta a absorção desse íon metálico.Galactomannans can be employed in food industries to modify the final rheological properties of the products. Since they are not absorbed by the living organisms they can also be used in dietary foods. The equilibria involving the interactions of Fe(III) and galactomannans and arabinogalactan of several leguminous plants were characterized by potentiometric titrations and EPR spectroscopy. The log of the equilibrium constants for the formation of ML species, where M is the metal ion and L is the monomeric unit of the biopolymers, were 15.4, 14.1 and 18.5, for the galactomannans of C. fastuosa, L. leucocephala and S. macranthera, respectively. Log K values for protonated species (MHL) were 3.1, 3.3, and were not detected for the galactomannan of S. macranthera. The log K values for the formation of ML 2 were 14.1, 13.3 and 15.2, respectively. Early formation of insoluble products in the equilibrium with arabinogalactan and Fe(III) prevented acquisition of reliable data. The solid complexes assays showed a great dipolar interaction between two Fe(III) ions in the inner structure of the biopolymer which increased as the degree of substitution of the galactomannan decreased, and also showed the resulting thermal stability. The complexes impart a new possibility of providing essential metal ions in dietary foods since decomplexation of the complexes can occur at different pH values existing in the human body.

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“…Protection of cells from apoptosis may have been another factor responsible for faster recovery in cultures containing hyaluronate. Hyaluronate preparations differing in molecular weight and some that have been chemically modified are widely used in the clinic as nonimmunogenic viscoelastic transplants with anti-inflammatory, cell protective, lubricating, and water-storing properties (9,10,(25)(26)(27)(28). Its mechanism of modulating the dynamics of tissue healing is of interest in basic research and has clinical implications.…”

Section: Discussionmentioning

confidence: 99%

In vitro model of “wound healing” analyzed by laser scanning cytometry: Accelerated healing of epithelial cell monolayers in the presence of hyaluronate

et al. 2003

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BackgroundIn vitro models of “wound healing” rely on analysis of confluent cell cultures that are mechanically wounded, e.g., by scratching the cell monolayer. Damage and removal of cells during wounding provides mitogenic signals to the adjacent cells and induces their migration to close the wound. The progress of healing is generally estimated by microscopy or time‐lapse cinematography by assessing cell proliferation and/or migration that leads to the wound closure.MethodsThe aim of the present study was to adapt laser scanning cytometry (LSC) to measure cellular changes related to damage and recovery of a monolayer of primary epithelial cells from rat kidneys growing with and without hyaluronate (∼6 × 106 average molecular weight). Because x–y coordinates of the cell position on the slide were recorded by LSC, the apoptotic and proliferative changes in individual cells induced by wounding and wound closure could be correlated, by multiparameter analysis, with the cell location with respect to the wound.ResultsThe initial change, observed as soon as 4 h after scratching and seen among the cells at the wound edge, was the appearance of apoptotic cells, characterized by cell shrinkage, typically condensed chromatin, and activation of caspases, the latter detected by binding of fluorochrome‐labeled inhibitor of caspases. Their frequency was reduced to up to sixfold in the presence of hyaluronate. Cell proliferation, measured by frequency of cells incorporating bromodeoxyuridine, also reflected by percentage of cells in S, G2, and mitosis, was higher in proximity of the wound but was not significantly affected by hyaluronate. However, the monolayer gap closure was accelerated in the presence of hyaluronate.ConclusionsBy offering the means to measure apoptosis and proliferation in relation to the cell position (distance) with respect to the wound in cell monolayer and to relocate them for visual inspection, LSC is uniquely suited to quantitatively analyze in vitro the process of wound healing. Hyaluronate, the ubiquitous component of intercellular matrix, preparations of which are being used in the clinic to suppress inflammatory reactions in tissues and promote healing, accelerated the healing process by protecting cells from apoptosis and stimulating cell migration to close the gap in the cell monolayer. Cytometry Part A 53A:1–8, 2003. © 2003 Wiley‐Liss, Inc.

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Reduction of adhesion formation by postoperative administration of ionically cross-linked hyaluronic acid

Cited by 89 publications

References 5 publications

The prevention of peritoneal adhesions by in situ cross-linking hydrogels of hyaluronic acid and cellulose derivatives

The prevention of peritoneal adhesions by in situ cross-linking hydrogels of hyaluronic acid and cellulose derivatives

Fe (III) - Galactomannan Solid and Aqueous Complexes: Potentiometric, EPR Spectroscopy and Thermal Data

In vitro model of “wound healing” analyzed by laser scanning cytometry: Accelerated healing of epithelial cell monolayers in the presence of hyaluronate

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