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Foreign body response to subcutaneous implants in diabetic rats.

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-?-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.

SUBMITTER: Socarras TO

PROVIDER: S-EPMC4220951 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Foreign body response to subcutaneous implants in diabetic rats.

Socarrás Teresa Oviedo TO Vasconcelos Anilton C AC Campos Paula P PP Pereira Nubia B NB Souza Jessica P C JP Andrade Silvia P SP

PloS one 20141105 11

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 diabet ...[more]

PMID: 25372281

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Project description:The foreign body response (FBR) to nitric oxide (NO)-releasing subcutaneous implants was compared between healthy and streptozotocin-induced diabetic swine by evaluating inflammation, collagen capsule formation, and angiogenesis. Steel wire substrates were first modified with polyurethane membranes capable of diverse NO-release kinetics (NO fluxes and release durations of 0.8-630.0 pmol cm-2 s-1 and 2-13 d, respectively). The NO-releasing materials were implanted in the subcutis for 3, 10, or 25 d for histological and immunohistochemical evaluation of the FBR. A delayed, more severe inflammatory response to control (i.e., non-NO-releasing) implants was observed in diabetic pigs relative to healthy swine. Regardless of the animal disease state, each NO-releasing implant tested elicited reduced inflammation compared to controls at both 3 and 10 d. However, only the NO-release materials capable of releasing low NO fluxes (0.8-3.3 pmol cm-2 s-1) for 7-13 d durations mitigated the inflammatory response at 25 d. Using immunohistochemical staining for the endothelial cell surface marker CD-31, we also observed poor blood vessel development at non-NO-releasing implants in diabetic swine. Relative to controls, NO-releasing implants with the longest NO-release duration (13 d) increased blood vessel densities by 47.1 and 70.4% in the healthy and diabetic pigs, respectively. In the healthy model, tissues surrounding the long NO-release materials contained sparse amounts of collagen, whereas implants with shorter NO-release durations (2, 3, and 7 d) were characterized with a dense collagen encapsulation layer, similar to controls. Collagen deposition in diabetic swine was inhibited, and unaffected by NO. These results emphasize several key differences in the FBR in the setting of acute onset diabetes. The observation that NO release counteracts the more severe FBR in diabetic swine while simultaneously promoting tissue integration may help guide the design of medical implants (e.g., glucose sensors) with improved performance for diabetes management.

Project description:Biodegradable plates have been used extensively in fracture fixation since the 1960s. They rarely cause stress-protection atrophy or problems requiring secondary plate removal, common complications seen with metallic plates. However, aseptic foreign-body reactions have been reported, sometimes years after the original implantation. Both inadequate polymer degradation and debris accumulation have been implicated as causes. The current generation of commercial biodegradable plates is formulated to minimize this complication by altering the ratio of polylactic and polyglycolic acids. This in vivo study compares the degree of local foreign-body reaction of two commercially available resorbable plates in rabbits. Two types of biodegradable plates were examined: poly(D/L)lactide acid (PDLLA) and polylactide-co-glycolide acid (PLGA). Each plate was placed into a periosteal pericalvarial pocket created beneath the anterior or posterior scalp of a rabbit. Humane killing occurred at 3, 6, and 12 months postoperatively. Foreign-body reaction was evaluated histologically. The PDLLA plates demonstrated marked local foreign-body reactions within the implant capsule as early as 3 months after implantation, with presence of inflammatory cells and granulomatous giant cells in close association with the implant material. All local foreign-body reactions were subclinical with no corresponding tissue swelling requiring drainage. PLGA plates did not demonstrate any signs of inflammatory reactions. In addition, the PLGA plates did not appear to resorb or integrate at 12 months. Neither PDLLA nor PLGA plates demonstrated inflammation of the soft tissue or adjacent bone outside the implant capsule. In our study, the PDLLA plates demonstrated histological evidence of foreign-body reaction that is confined within the implant capsule, which was not seen with the PLGA plates. This finding may be attributable to the lack of significant resorption seen in the PLGA plates. Both PDLLA and PLGA plates were biocompatible with the rabbit tissue environment and should be considered for continued use in craniofacial, maxillofacial, and orthopedic reconstruction.

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Foreign body response to subcutaneous implants in diabetic rats.

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Foreign body response to subcutaneous implants in diabetic rats.

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