In situ forming oxidised hyaluronic acid/adipic acid dihydrazide hydrogel for prevention of epidural fibrosis after laminectomy

Hu, Ming-Hsiao; Yang, Kai Chiang; Sun, Yi‐Kun; Chen, Y C; Yang, Shu Hua; Lin, Feng-Huei

doi:10.22203/ecm.v034a19

Cited by 20 publications

(20 citation statements)

References 27 publications

(37 reference statements)

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“…Despite extensive research on cytotoxicity (effects on cell proliferation/viability) of aldehyde-modified polysaccharides and ADH, genotoxicity studies are still scarce, in particular, on ADHreticulated polyaldehyde-based hydrogels (Bouhadir, Hausman, & Mooney, 1999;Hu et al, 2017;Maia et al, 2009;Schramm et al, 2012;Su, Chen, & Lin, 2010). Genotoxicity is an important endpoint of the safety assessment of regulated products, but no single test is available to detect all types of genotoxicity.…”

Section: Discussionmentioning

confidence: 99%

In vitro genotoxicity assessment of an oxidized dextrin‐based hydrogel for biomedical applications

Pereira

Fraga

Silva

et al. 2018

J of Applied Toxicology

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Hydrogels are three‐dimensional, crosslinked networks of hydrophilic polymers swollen with a large amount of water or biological fluids, without dissolving. Dextrin, a low‐molecular‐weight carbohydrate composed by glucose residues, has been used to develop an injectable hydrogel for biomedical applications. Dextrin was first oxidized to introduce aldehyde groups, which then reticulate with adipic acid dihydrazide, forming the dextrin‐based hydrogel (HG). The HG and its components were tested for cyto‐ and genotoxicity according to the International Standard ISO 10993‐3 on the biological evaluation of medical devices. To assess genotoxicity, a battery of in vitro genotoxicity tests employing both eukaryotic and prokaryotic models was performed: comet assay, cytokinesis‐block micronucleus assay and Ames test. Our data revealed that the HG (IC50 = 2.8 mg/mL) and oxidized dextrin by itself (IC50 = 1.2 mg/mL) caused a concentration‐dependent decrease in cellular viability of human lymphoblastoid TK6 cells after 24 hours of exposure to the test agents. However, these concentrations are unlikely to be reached in vivo. In addition, no significant increase in the DNA and chromosomal damage of TK6 cells exposed to non‐cytotoxic concentrations of the HG and its isolated components was detected. Furthermore, neither the HG nor its metabolites exerted a mutagenic effect in different of Salmonella typhimurium strains and in an Escherichia coli mix. Our data demonstrated the genocompatibility of the HG (up to 3.5 mg/mL) for biomedical applications. To our best acknowledge, this is the first report with a detailed genotoxicity assessment of an aldehyde‐modified polysaccharide/adipic acid dihydrazide hydrogel.

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Section: Discussionmentioning

confidence: 99%

In vitro genotoxicity assessment of an oxidized dextrin‐based hydrogel for biomedical applications

Pereira

Fraga

Silva

et al. 2018

J of Applied Toxicology

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“…It can be expected that medicines discharged out of the facet joint failed to reach properly pain-generating sites and showed a reduced effect on pain relief due to sequelae such as epidural adhesion after back surgery. 20 However, Hwang SY et al revealed that there was no correlation between the degree of spreading to the epidural space and the FJI effect. 5 Furthermore, many studies have also reported that the severity of spinal stenosis or facet arthropathy were not related to ESI or FJI effect.…”

Section: Discussionmentioning

confidence: 99%

The effect of facet joint injection on lumbar spinal stenosis with radiculopathy

et al. 2018

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Objectives:Facet Joint Injection (FJI) is known to be effective in axial back pain, but the purpose of this study was to assess the effects of FJI on patients treated with it among those with Lumbar Spinal Stenosis (LSS).Methods:We conducted a retrospective database analysis and investigated electronic medical records of 125 LSS patients treated with FJI in the pain clinic of Chungbuk National University Hospital from November 2, 2016 to July 31, 2017. Sex, age, histories of low back surgery, complaining of neurogenic claudication, symptomatic sites of patients, FJI sites, number of sites of FJI, triamcinolone dosage, Numeric Rating Scale (NRS) before and after treatment, facet joint capsule rupture during treatment, and improvement of neurogenic claudication after treatment, were examined.Results:Among 125 patients, we investigated 91 patients who met the criteria. There was significant difference in NRS before and after treatment (p<0.000). Forty one patients with reduction of NRS more than 30% after FJI were allocated to effect group. FJI was more effective in patients who did not have the surgery (p=0.044), as well as those who showed an improved neurogenic claudication after treatment (p=0.001). Other measured values did not show statistical significances.Conclusions:FJI has relatively a lower risk and is simpler in terms of techniques than other interventional treatments performed within the spinal canal. Therefore, FJI may be another interventional treatment option in patients with pain by LSS. In the future, studies for FJI indication in LSS patients should be additionally required.

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“…6 g oxi-HA was dissolved in 100 ml of PBS and then added into 60 ml of ADH solution (oxi-HA-ADH). Finally, an adequate amount of oxi-Clenbuterol was added to complete the synthesis of injectable HAC thermo-sensitive hydrogel (15)(16)(17)(18)20).…”

Section: The Preparation Of Injectable Clenbuterol-modified Hyaluronamentioning

confidence: 99%

“…The release profile in vitro was used to soak HAC in PBS solution for some time and then check the Clenbuterol level in the supernatant by UV-Vis. Those comprehensive data were previously published in the materialrelated journal (15)(16)(17)(18). In the manuscript, we focused more on the results of the following: cell viability, cytotoxicity, lipolysis on a cellular level, chronic toxicity, body weight control, whole-body adipose tissue, gonadal fat tissue, blood analysis, serological analysis, and sectioning examination of internal organs.…”

Section: Introductionmentioning

confidence: 99%

Oxidized Hyaluronic Acid Hydrogels as a Carrier for Constant-Release Clenbuterol Against High-Fat Diet-Induced Obesity in Mice

Chen

Lin

2021

Front. Endocrinol.

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The global obesity population is increasing year-by-year, and the related cost is sharply increasing annually. There are several methods available to combat obesity; however, there is a lack of a single tool that is both safe and efficacious. The use of Clenbuterol in bodybuilding and by professional athletes is controversial owing to its side effects, including hepatotoxicity. This study administered Clenbuterol at a much lower dose than the established safety level, and rather than through oral administration, the treatments were delivered through controlled-release intra-adipose injection. The different dosing and mode of administration will lower the risk of side effects, increase the safety profile, and could facilitate use in the anti-obesity market. A thermo-sensitive hydrogel was used as the carrier uploaded with Clenbuterol to achieve controlled-release. In the in vitro study, the developed new formulae were not cytotoxic to 3T3-L1 cells and could inhibit lipogenesis effectively. In the animal study, the mice were fed a high-fat diet and treated with Clenbuterol by oral administration, or injected with Clenbuterol-modified hyaluronate hydrogel (HAC) regularly. Both groups showed reduction in whole-body, visceral, and gonadal fat contents and body weight. The abdominal fat was analyzed using MRI imaging in adipose mode and water mode. The abdominal fat ratio in the mice treated with normal diet and those given intra-adipose injections with HAC had the lowest value among the test groups. The mice treated with high-fat diet (HFD) showed the highest value of 53.78%. The chronic toxicity in-vivo test proved that controlled-release injections of 2–10 µg Clenbuterol daily were safe, as demonstrated in the blood elements and serological analyses. This study developed a new and promising method for anti-obesity treatment, using a monthly intra-adipose controlled-release injection of HAC. The developed new formulae of Clenbuterol not only effectively decreased body weight and body fat content but also inhibited lipogenesis on the harvested visceral tissue and reduced adipose tissue around the gonadal fat area. The side effects induced by traditional oral administration of Clenbuterol were not observed in this research; this has excellent potential to be a useful tool for future obesity treatment without safety concerns.

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In situ forming oxidised hyaluronic acid/adipic acid dihydrazide hydrogel for prevention of epidural fibrosis after laminectomy

Cited by 20 publications

References 27 publications

In vitro genotoxicity assessment of an oxidized dextrin‐based hydrogel for biomedical applications

In vitro genotoxicity assessment of an oxidized dextrin‐based hydrogel for biomedical applications

The effect of facet joint injection on lumbar spinal stenosis with radiculopathy

Oxidized Hyaluronic Acid Hydrogels as a Carrier for Constant-Release Clenbuterol Against High-Fat Diet-Induced Obesity in Mice

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