Dataset Information

Preparation of a Cross-Linked Cartilage Acellular-Matrix Film and Its In Vivo Evaluation as an Antiadhesive Barrier.

ABSTRACT: In this paper, a cartilage acellular-matrix (CAM) is chosen as a biomaterial for an effective antiadhesive barrier to apply between injured tissue and healthy tissues or organs. CAM is cross-linked using glutaraldehyde to create a cross-linked CAM (Cx-CAM) film. Cx-CAM has higher elastic modulus and toughness and more hydrophobic surface properties than CAM before cross-linking. Small intestinal submucosa (SIS), cross-linked SIS (Cx-SIS) as a negative control, and Seprafilm as a positive control are used in an experiment as adhesion barriers. Human umbilical vein endothelial cells (HUVECs) on SIS, Cx-SIS, or in a culture plate get attached and effectively proliferate for 7 days, but Cx-CAM and Seprafilm allow for little or no attachment and proliferation of HUVECs, thus manifesting antiadhesive and antiproliferative effects. In animals with surgical damage to the peritoneal wall and cecum, Cx-CAM and Seprafilm afford little adhesion and negligible inflammation after seven days, as confirmed by hematoxylin and eosin staining and macrophage staining, in contrast to an untreated-injury model, SIS, or Cx-SIS film. Cx-CAM significantly suppresses the formation of blood vessels between the peritoneal wall and cecum, as confirmed by CD31 staining. Overall, the newly designed Cx-CAM film works well as an antiadhesion barrier and has better anti-tissue adhesion efficiency.

SUBMITTER: Park JY

PROVIDER: S-EPMC6419041 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Preparation of a Cross-Linked Cartilage Acellular-Matrix Film and Its In Vivo Evaluation as an Antiadhesive Barrier.

Park Joon Yeong JY Song Bo Ram BR Lee Jin Woo JW Park Seung Hun SH Kang Tae Woong TW Yun Hee-Woong HW Park Sang-Hyug SH Min Byoung Hyun BH Kim Moon Suk MS

Polymers 20190202 2

In this paper, a cartilage acellular-matrix (CAM) is chosen as a biomaterial for an effective antiadhesive barrier to apply between injured tissue and healthy tissues or organs. CAM is cross-linked using glutaraldehyde to create a cross-linked CAM (Cx-CAM) film. Cx-CAM has higher elastic modulus and toughness and more hydrophobic surface properties than CAM before cross-linking. Small intestinal submucosa (SIS), cross-linked SIS (Cx-SIS) as a negative control, and Seprafilm as a positive control ...[more]

PMID: 30960232

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Project description:BackgroundSprifermin (recombinant human fibroblast growth factor 18) is in clinical development as a potential disease-modifying osteoarthritis drug (DMOAD). In vitro studies have shown that cartilage regenerative properties of sprifermin involve chondrocyte proliferation and extracellular matrix (ECM) production. To gain further insight into the process of sprifermin in the cartilage tissue, this study aimed at investigating the ECM turnover of articular cartilage explants in a longitudinal manner.MethodsBovine full-depth articular cartilage explants were stimulated with sprifermin or placebo at weekly intervals, similar to the dosing regimen used in clinical trials. Pre-culturing with oncostatin M and tumour necrosis factor-α, was also used to induce an inflammatory state before treatment. Metabolic activity was measured using AlamarBlue, and chondrocyte proliferation was visualized by immuno-histochemical detection of proliferating cell nuclear antigen. ECM turnover was quantified by biomarker ELISAs; ProC2 reflecting type II collagen formation, CS846 reflecting aggrecan formation, active MMP9, C2M and AGNx2 reflecting matrix metalloproteinase activity, and AGNx1 reflecting aggrecanase activity.ResultsSprifermin was able to reach the chondrocytes through the extracellular matrix, as it increased cell proliferation and metabolic activity of explants. ProC2 and CS846 was dose-dependently increased (P < 0.05) by sprifermin compared to placebo, while C2M and AGNx2 were unaffected, active MMP9 was slightly decreased, and AGNx1 was slightly increased. Over the course of treatment, the temporal order of ECM turnover responses was AGNx1, then ProC2, followed by CS846 and MMP9. Pro-inflammatory activation of the explants diminished the ECM turnover responses otherwise observed under non-inflammatory conditions.ConclusionsThe data suggest that sprifermin has chondrogenic effects on articular cartilage ex vivo, exerted through a sequential process of ECM turnover; aggrecan degradation seems to occur first, while type II collagen and aggrecan production increased at a later time point. In addition, it was observed that these chondrogenic effects are dependent on the inflammatory status of the cartilage prior to treatment.

Dataset Information

Preparation of a Cross-Linked Cartilage Acellular-Matrix Film and Its In Vivo Evaluation as an Antiadhesive Barrier.

Publications

Preparation of a Cross-Linked Cartilage Acellular-Matrix Film and Its In Vivo Evaluation as an Antiadhesive Barrier.

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