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Foreign body response to subcutaneous implants in diabetic rats.

Socarrás TO, Vasconcelos AC, Campos PP, Pereira NB, Souza JP, Andrade SP - PLoS ONE (2014)

Bottom Line: Implantation of synthetic matrices and biomedical devices in diabetic individuals has become a common procedure to repair and/or replace biological tissues.Intra-implant levels of hemoglobin and vascular endothelial growth factor were not different after diabetes when compared with normoglycemic counterparts.All fibrogenic markers (transforming growth factor beta 1 levels, collagen deposition, fibrous capsule thickness, and foreign body giant cells) decreased after diabetes, whereas apoptosis (TUNEL) increased.

View Article: PubMed Central - PubMed

Affiliation: Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Department of Livestock Sciences, University of Córdoba, Montería, Córdoba, Colombia.

ABSTRACT
Implantation of synthetic matrices and biomedical devices in diabetic individuals has become a common procedure to repair and/or replace biological tissues. However, an adverse foreign body reaction that invariably occurs adjacent to implant devices impairing their function is poorly characterized in the diabetic environment. We investigated the influence of this condition on the abnormal tissue healing response in implants placed subcutaneously in normoglycemic and streptozotocin-induced diabetes in rats. In polyether-polyurethane sponge discs removed 10 days after implantation, the components of the fibrovascular tissue (angiogenesis, inflammation, fibrogenesis, and apoptosis) were assessed. Intra-implant levels of hemoglobin and vascular endothelial growth factor were not different after diabetes when compared with normoglycemic counterparts. However, there were a lower number of vessels in the fibrovascular tissue from diabetic rats when compared with vessel numbers in implants from non-diabetic animals. Overall, the inflammatory parameters (neutrophil accumulation--myeloperoxidase activity, tumor necrosis factor alpha, and monocyte chemotactic protein-1 levels and mast cell counting) increased in subcutaneous implants after diabetes induction. However, macrophage activation (N-acetyl-β-D-glucosaminidase activity) was lower in implants from diabetic rats when compared with those from normoglycemic animals. All fibrogenic markers (transforming growth factor beta 1 levels, collagen deposition, fibrous capsule thickness, and foreign body giant cells) decreased after diabetes, whereas apoptosis (TUNEL) increased. Our results showing that hyperglycemia down regulates the main features of the foreign body reaction induced by subcutaneous implants in rats may be relevant in understanding biomaterial integration and performance in diabetes.

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Histological analysis of 10-day old implants from non-diabetic and diabetic rats.Representative histological sections stained with H&E of fibrovascular tissue from diabetic (A) and non diabetic (B) rats. The pores of the sponge matrix, seen as triangular shapes, is composed of microvessels (C), spindle-shaped fibroblasts (D) and inflammatory infiltrate consisting of neutrophils (E), macrophages (F), and foreign body giant cells (G). Dilated microvessels and low cellularity were characteristics of implants from diabetic rats (H). Data are expressed as means ± SEM. *Significant difference between non-diabetic and diabetic; p<0.05; Mann-Whitney test. NSC, non-diabetic implant; DSC, diabetic implant; scale bar, 50 µm.
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pone-0110945-g001: Histological analysis of 10-day old implants from non-diabetic and diabetic rats.Representative histological sections stained with H&E of fibrovascular tissue from diabetic (A) and non diabetic (B) rats. The pores of the sponge matrix, seen as triangular shapes, is composed of microvessels (C), spindle-shaped fibroblasts (D) and inflammatory infiltrate consisting of neutrophils (E), macrophages (F), and foreign body giant cells (G). Dilated microvessels and low cellularity were characteristics of implants from diabetic rats (H). Data are expressed as means ± SEM. *Significant difference between non-diabetic and diabetic; p<0.05; Mann-Whitney test. NSC, non-diabetic implant; DSC, diabetic implant; scale bar, 50 µm.

Mentions: In histological sections of the implants (H&E), the synthetic matrix induced the formation of a fibrovascular tissue that differed in important ways between implants from diabetic and non-diabetic rats. In normoglycemic rats, the granulation tissue that filled the subcutaneous matrix was composed of spindle-shaped fibroblasts, microvessels, and a dense inflammatory infiltrate containing macrophages, neutrophils, and foreign body giant cells embedded in an extracellular matrix. However, in implants from diabetic rats, the connective tissue was immature with little matrix deposition. A lower number of blood vessels and cellularity was observed when compared with implants from non-diabetic animals. One striking difference between both implants was the vasodilation observed in the microvasculature in the hyperglycemic environment when compared with that in normoglycemic rats (Fig. 1A–H).


Foreign body response to subcutaneous implants in diabetic rats.

Socarrás TO, Vasconcelos AC, Campos PP, Pereira NB, Souza JP, Andrade SP - PLoS ONE (2014)

Histological analysis of 10-day old implants from non-diabetic and diabetic rats.Representative histological sections stained with H&E of fibrovascular tissue from diabetic (A) and non diabetic (B) rats. The pores of the sponge matrix, seen as triangular shapes, is composed of microvessels (C), spindle-shaped fibroblasts (D) and inflammatory infiltrate consisting of neutrophils (E), macrophages (F), and foreign body giant cells (G). Dilated microvessels and low cellularity were characteristics of implants from diabetic rats (H). Data are expressed as means ± SEM. *Significant difference between non-diabetic and diabetic; p<0.05; Mann-Whitney test. NSC, non-diabetic implant; DSC, diabetic implant; scale bar, 50 µm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4220951&req=5

pone-0110945-g001: Histological analysis of 10-day old implants from non-diabetic and diabetic rats.Representative histological sections stained with H&E of fibrovascular tissue from diabetic (A) and non diabetic (B) rats. The pores of the sponge matrix, seen as triangular shapes, is composed of microvessels (C), spindle-shaped fibroblasts (D) and inflammatory infiltrate consisting of neutrophils (E), macrophages (F), and foreign body giant cells (G). Dilated microvessels and low cellularity were characteristics of implants from diabetic rats (H). Data are expressed as means ± SEM. *Significant difference between non-diabetic and diabetic; p<0.05; Mann-Whitney test. NSC, non-diabetic implant; DSC, diabetic implant; scale bar, 50 µm.
Mentions: In histological sections of the implants (H&E), the synthetic matrix induced the formation of a fibrovascular tissue that differed in important ways between implants from diabetic and non-diabetic rats. In normoglycemic rats, the granulation tissue that filled the subcutaneous matrix was composed of spindle-shaped fibroblasts, microvessels, and a dense inflammatory infiltrate containing macrophages, neutrophils, and foreign body giant cells embedded in an extracellular matrix. However, in implants from diabetic rats, the connective tissue was immature with little matrix deposition. A lower number of blood vessels and cellularity was observed when compared with implants from non-diabetic animals. One striking difference between both implants was the vasodilation observed in the microvasculature in the hyperglycemic environment when compared with that in normoglycemic rats (Fig. 1A–H).

Bottom Line: Implantation of synthetic matrices and biomedical devices in diabetic individuals has become a common procedure to repair and/or replace biological tissues.Intra-implant levels of hemoglobin and vascular endothelial growth factor were not different after diabetes when compared with normoglycemic counterparts.All fibrogenic markers (transforming growth factor beta 1 levels, collagen deposition, fibrous capsule thickness, and foreign body giant cells) decreased after diabetes, whereas apoptosis (TUNEL) increased.

View Article: PubMed Central - PubMed

Affiliation: Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Department of Livestock Sciences, University of Córdoba, Montería, Córdoba, Colombia.

ABSTRACT
Implantation of synthetic matrices and biomedical devices in diabetic individuals has become a common procedure to repair and/or replace biological tissues. However, an adverse foreign body reaction that invariably occurs adjacent to implant devices impairing their function is poorly characterized in the diabetic environment. We investigated the influence of this condition on the abnormal tissue healing response in implants placed subcutaneously in normoglycemic and streptozotocin-induced diabetes in rats. In polyether-polyurethane sponge discs removed 10 days after implantation, the components of the fibrovascular tissue (angiogenesis, inflammation, fibrogenesis, and apoptosis) were assessed. Intra-implant levels of hemoglobin and vascular endothelial growth factor were not different after diabetes when compared with normoglycemic counterparts. However, there were a lower number of vessels in the fibrovascular tissue from diabetic rats when compared with vessel numbers in implants from non-diabetic animals. Overall, the inflammatory parameters (neutrophil accumulation--myeloperoxidase activity, tumor necrosis factor alpha, and monocyte chemotactic protein-1 levels and mast cell counting) increased in subcutaneous implants after diabetes induction. However, macrophage activation (N-acetyl-β-D-glucosaminidase activity) was lower in implants from diabetic rats when compared with those from normoglycemic animals. All fibrogenic markers (transforming growth factor beta 1 levels, collagen deposition, fibrous capsule thickness, and foreign body giant cells) decreased after diabetes, whereas apoptosis (TUNEL) increased. Our results showing that hyperglycemia down regulates the main features of the foreign body reaction induced by subcutaneous implants in rats may be relevant in understanding biomaterial integration and performance in diabetes.

Show MeSH
Related in: MedlinePlus