Pro - inflammatory cytokines and metalloproteinase activation in polypropylene mesh implant in rat subcutaneous tissue

ABSTRACT Aims and Objectives: Polypropylene meshes have been increasingly adopted for correction of pelvic organ prolapse due to its lower recurrence rate when compared to surgeries without meshes. The study of the interaction of these materials with the host tissue may contribute to the development of materials with best biocompatibility and, consequently, less complication rates. Materials and Methods: The present study compares the inflammatory reaction of standard-weight (SW) and lightweight (LW) meshes (72 g/m216g/m2 respectively), implanted in the abdomen of 20 adult rats, which were euthanized in four or 30 days. Quantification of pro-inflammatory markers, IL-1 and TNF-α, and of metalloproteinases, MMP2 and MMP3, were carried out through immunohistochemistry with AxioVision® software. Results: There were no significant differences in the quantification of IL-1 and TNF-α in LW versus SW meshes. However, IL-1 quantification increased along time (30 days >4 days, p=0.0269). Also, MMP-2 quantification was similar to SW and LW and both presented a significant increase along time (30 days >4 days, p <0.0001). MMP-3 quantification also showed no difference between the SW and LW groups, but increased along time (30 days >4 days, p=0.02). Conclusions: Mesh's density did not influence the quantification of pro-inflammatory cytokines IL-1 and TNF-α and metalloproteinases 2 and 3. The increased expression of IL-1, MMP-2 and MMP-3 over time could represent a longstanding inflammatory response after PP mesh implantation. Possibly, the occurrence of adverse events following PP prosthetic implants can be influenced by other factors, not solely related to the amount of implanted material.

Idiosyncratic reaction after injection of polyacrylate - polyalcohol copolymer

ABSTRACT Context: Polyacrylate-polyalcohol copolymer is a synthetic product, non-biodegradable, with low rate of therapeutic failure and lower incidence of reactions at the site of injection, when compared to biodegradable agents. We report an unprecedent, exuberant and persistent inflammatory reaction following injection of that substance. Patient: a 17 years-old patient with vesico-ureteral reflux and complete pyelocaliceal right duplication was submitted to treatment with polyacrylate-polyalcohol copolymer (STING technique). In the seventh day of post-operatory, she presented intense dysuria and hypogastric pain, without laboratory exams alterations; a symptomatic treatment was started. After two months, the symptoms persisted and an ultrasound detected thickening of bladder wall close to the uretero-vesical junction. After that exam, a cystostopic biopsy showed epithelial hyperplasia with increased edema of lamina propria, suggesting an adverse reaction to the polymer. After four months, there was complete remission, but the reflux persisted with the same grade. Hypothesis: This is an unprecedent reaction following injection of this copolymer. The presence of characteristics such as absence of infection, temporal relation between treatment and beginning of symptoms, and detection of epithelial hyperplasia at the local of injection reinforce the hypothesis of association of the substance and adverse reaction. In that patient, important complains motivated early investigation of urinary tract, that confirmed those aspects. Maybe if that reaction had occurred in patients with lower capacity of expression (such as in infants) it would be unnoticed.

Host inflammatory response to polypropylene implants: insights from a quantitative immunohistochemical and birefringence analysis in a rat subcutaneous model

ABSTRACT Objectives To describe acute and sub acute aspects of histological and immunohistochemical response to PP implant in a rat subcutaneous model based on objective methods. Materials and Methods Thirty rats had a PP mesh subcutaneously implanted and the same dissection on the other side of abdomen but without mesh (sham). The animals were euthanized after 4 and 30 days. Six slides were prepared using the tissue removed: one stained with hematoxylin-eosin (inflammation assessment); one unstained (birefringence evaluation) and four slides for immunohistochemical processing: IL-1 and TNF-α (pro-inflammatory cytokines), MMP-2 (collagen metabolism) and CD-31 (angiogenesis). The area of inflammation, the birefringence index, the area of immunoreactivity and the number of vessels were objectively measured. Results A larger area of inflammatory reaction was observed in PP compared to sham on the 4th and on the 30th day (p=0.0002). After 4 days, PP presented higher TNF (p=0.0001) immunoreactivity than sham and no differences were observed in MMP-2 (p=0.06) and IL-1 (p=0.08). After 30 days, a reduction of IL-1 (p=0.010) and TNF (p=0.016) for PP and of IL-1 (p=0.010) for sham were observed. Moreover, area of MMP-2 immunoreactivity decreased over time for PP group (p=0.018). Birefringence index and vessel counting showed no differences between PP and sham (p=0.27 and p=0.58, respectively). Conclusions The implantation of monofilament and macroporous polypropylene in the subcutaneous of rats resulted in increased inflammatory activity and higher TNF production in the early post implant phase. After 30 days, PP has similar cytokines immunoreactivity, vessel density and extracellular matrix organization.

Rat subcutaneous tissue response to modified Portland Cement, a new mineral trioxide aggregate

The purpose of this study was compare the biocompatibility of modified Portland cement (CPM) and mineral trioxide aggregate (MTA) in a subcutaneous rat model. Twenty-four male Wistar rats were used. Three silicon tubes were placed on the dorsal subcutaneous tissue of each animal: one tube contained MTA, one tube contained CPM and the other was an empty tube. The rats were sacrificed in 3 groups of 8 animals at 7, 14 and 30 postoperative days, respectively. Tissue samples were fixed in 10 percent buffered formalin, embedded in paraffin, and serial sections were cut and stained with hematoxylin and eosin, Masson Trichrome and Luna's stain. At day 7, the empty tubes displayed a mild inflammatory infiltrate. In the CPM group, an inflammatory infiltrate was observed with some eosinophils and immature connective tissue. The MTA group showed a similar infiltrate without eosinophils and presence of abundant necrotic tissue and numerous multinucleate foreign body giant cells. At day 14, the chronic infiltrate with eosinophils persisted when in contact with CPM. In the MTA group, necrosis and distant giant cells could still be seen. At day 30, all 3 groups showed mature fibrous collagenous tissue. These findings indicate a different response to the materials evaluated in this study. Although, MTA and CPM induced a chronic inflammatory infiltrate, necrosis and multinucleated foreign body giant cells predominated in the MTA group, while in the CPM group numerous eosinophils were seen at all the observational periods.

O propósito deste estudo foi comparar a biocompatibilidade do cimento Portland modificado (CPM) com agregado de trióxido mineral (MTA) no subcutâneo de um modelo murino. Foram usados 24 ratos Wistar macho. No tecido subcutâneo dorsal de cada animal se colocaram 3 tubos de silicone. Um contendo MTA, outro CPM e o último vazio. Os animais foram sacrificados em 3 grupos de 8 aos 7, 14 e 30 dias. As amostras se fixaram em formol e se coloriram com hematoxilina - eosina, Masson e Luna. No dia 7 os tubos vazios mostraram uma leve infiltração de células inflamatórias. No grupo CPM, se observou um infiltrado inflamatório com alguns eosinófilos e tecido conectivo imaturo. O grupo MTA mostrou um infiltrado similar sem eosinófilos e abundante necrose de tecido e numerosas células gigantes multinucleadas do tipo corpo estranho. Ao dia 14, o infiltrado crônico com eosinófilos persistiu em contato com CPM. No grupo MTA, a necrose e células multinucleadas afastadas ainda se podiam observar. Ao dia 30, os 3 grupos mostraram tecido fibroso maduro. Estes resultados mostram uma resposta diferente aos materiais avaliados no presente estudo. Apesar do que MTA e CPM causaram um infiltrado crônico, no grupo MTA predominou a necrose e as células gigantes, enquanto isso, no grupo CPM se observaram grandes quantidades de eosinófilos.