Thick Fibrous Capsule Research Articles

Biomaterial topography alters healing in vivo and monocyte/macrophage activation in vitro

The effect of biomaterial topography on healing in vivo and monocyte/macrophage stimulation in vitro was assessed. A series of expanded polytetrafluoroethylene (ePTFE) materials were characterized by increasing average intranodal distance of 1.2 μm (1.2-ePTFE), 3.0 μm (3.0-ePTFE), and 4.4 μm (4.4-ePTFE), but presented consistent surface chemistry with nonporous PTFE (np-PTFE). Subcutaneous implantation of 4.4-ePTFE into mice resulted in a statistically thinner capsule that appeared less organized and less dense than the np-PTFE response. In vitro, isolated monocytes/macrophages cultured on np-PTFE produced low levels of interleukin 1-beta (IL-1β), 1.2-ePTFE and 3.0-ePTFE stimulated intermediate levels, and 4.4-ePTFE stimulated a 15-fold increase over np-PTFE. Analysis of cDNA microarrays demonstrated that additional proinflammatory cytokines and chemokines, including IL-1β, interleukin 6, tumor necrosis factor alpha, monocyte chemotactic protein 1, and macrophage inflammatory protein 1-beta, were expressed at higher levels by monocytes/macrophages cultured on 4.4-ePTFE at 4 and 24 h, respectively. Expression ratios for several genes were quantified by RT-PCR and were consistent with those from the cDNA array results. These results demonstrate the effect of biomaterial topography on early proinflammatory cytokine production and gene transcription by monocytes/macrophages in vitro and decreased fibrous capsule thickness in vivo.

The effect of liposome‐delivered prednisolone on collagen density, myofibroblasts, and fibrous capsule thickness around silicone breast implants in rats

Capsular contracture is a potential adverse effect of breast implants. An inflammatory reaction is most likely the origin of fibrosis around the implant. It is possible that some substances may act to prevent this inflammatory reaction. Thus, our goal was to evaluate the effectiveness of local depot prednisolone phosphate-liposomes (PPL) on fibrous capsule formation around textured silicone breast implants. Shell prostheses (2 mL) were implanted in the right (plus PPL group) and left (plus saline solution, saline group) subcutaneous dorsum of 18 rats. In another 18 rats, the implants were positioned in the left of the back without any drug instillation (control group). In the PPL group, the capsule thickness (microm) and density (%) of collagen were significantly (p<0.0001) lower compared with the control group on days 35 and 90 postsurgery. Furthermore, in the PPL group, a significant reduction in myofibroblast count was observed on day 90 postsurgery (p<0.0001). In conclusion, a single dose of depot liposome-delivered prednisolone was effective at impairing capsule formation around the silicone implant. The results suggest a strong local and weak systemic effect of PPL on the fibrous tissue around silicone implants. To our knowledge, no study has yet assessed the effect of PPL on silicone breast implants.

Role of immune cells and inflammatory cytokines in regulation of fibrosis around silicone expander implants

This study aimed to investigate the progress of wound healing around silicone expander with particular emphasis on fibroblasts, myofibroblasts and collagen in the repair phase. Semi-quantitative evaluation of inflammatory cells and their cytokines, fibroblasts and myofibroblasts at the tissue-material interface was carried out. Commercially available silicone expander was implanted in gluteus muscle of young female Wistar rats for 3, 7, 14, 30, 90 and 180 days. Ultra high molecular weight polyethylene served as control. The cellular response was studied by immunohistochemistry and Transmission Electron Microscopy. A thick collagenous fibrous capsule was observed around the silicone expander at 180 days, with persistent myofibroblasts, lymphocytes and macrophages as compared to the thin fibrous encapsulation around the UHMWPE implants. The regulatory role of cytokines and immune cells in myofibroblast persistence in tissue-implant interface around silicone expander has been extensively studied. Results of this study indicate the need to elucidate the signaling molecules in the transition of fibroblast to myofibroblast around silicone expander implants.

Can renal oncocytoma be distinguished from chromophobe renal cell carcinoma by the presence of fibrous capsule?

The most important differential diagnosis of chromophobe renal cell carcinoma (CRCC) is renal oncocytoma. Due to overlapping morphological characteristics of renal oncocytoma and CRCC, particularly its eosinophilic variant, making a correct diagnosis can be challenging. To date, no data are available on the presence of the tumor fibrous capsule as a diagnostic feature in differentiating these tumors. The main purpose of this study was to establish the presence and compare the thickness of the tumor fibrous capsule between two tumor groups. A total of 37 tumors--18 cases of CRCC (three eosinophilic and 15 classic) and 19 cases of renal oncocytoma--were analyzed. Four slides of each tumor stained with hematoxylin and eosin were first scanned at low-power magnification (x40) to assess the presence of the capsule. If present, the capsule was measured in three different thickest areas at higher magnification (x200). The mean value of capsule thickness was calculated and taken into consideration. The capsule was present in 12 (66.7%) cases of CRCCs and in only two (10.5%) cases of renal oncocytomas. Statistical analysis showed significant difference between the presence of fibrous capsule in these two observed tumor groups (P = 0.001). Average thickness of capsule in CRCCs was 337.7 microm, and 115.4 microm in renal oncocytomas, but the median was not statistically significant (P = 0.198). Studies with a larger number of cases are needed to conclude if this characteristic could be a low-cost, reliable microscopic feature in differentiating between CRCC and renal oncocytoma.

Pectin‐coated titanium implants are well‐tolerated in vivo

Multiform coated titanium implants are widely used in orthopedic and dental surgery. In this study, we have investigated the reactivity of pectin-coated titanium samples implanted under the latissimus dorsi-muscle fascia of rats. Samples were coated with two enzyme treated apple pectins; modified hairy regions (MHR-A and MHR-B) that differed in chemical structure. Aminated (AMI) and uncoated titanium (Ti) served as controls. The thicknesses of the peri-implant fibrous tissue capsules formed 1 or 3 weeks after implantation were measured as indicative of possible inflammatory reactions toward the biomaterials. After 1 week, the MHR-B implant was surrounded by a thicker fibrous capsule (42.9 microm) than any of the other sample types: MHR-A (33.2 microm), AMI (32.5 microm), and Ti (32.3 microm), the last one being the only statistically significant difference. After 3 weeks, however, this difference disappeared; the capsule thicknesses around MHR-B and Ti implants had decreased to the values found for AMI and MHR-A. Additionally, the capsule formation represents merely a stromal rather than an inflammatory reaction, as indicated by the absence of activated macrophages or foreign body giant cells in the capsules. These results indicate for the first time the in vivo tolerability of covalently linked pectins, and suggest the feasibility of pectin-coated bone and dental implants for clinical use.

Calcium Aluminate, RGD-Modified Calcium Aluminate, and β-Tricalcium Phosphate Implants in a Calvarial Defect

Calcium aluminate (CaAl), arginine-glycine-aspartic acid-modified CaAl, and beta-tricalcium phosphate (TCP) implants were studied in a rat calvarial critical-sized defect model. The rates of newly formed bone and osteointegration were measured using 3 different methods: radiography, micro-computed tomography, and histologic examination. After 4 weeks, there was no new bone formed and no signs of osteointegration into the skull bone in the CaAl or arginine-glycine-aspartic acid-modified CaAl groups, and thick fibrous capsules were visible around the whole circumference of the implants in both groups. In the beta-TCP group, neovascularization of the implant was observed, which is consistent with the early phase of new bone formation. In addition, in the beta-TCP group, signs of implant integration into the host tissue were evident at 4 weeks. There was no soft tissue reaction around the beta-TCP implant. These observations suggest that more specific adhesion peptides may be needed to activate the bioinert CaAl implant and promote bone formation in the craniofacial skeleton.

Vascularization of wide pore agarose–gelatin cryogel scaffolds implanted subcutaneously in diabetic and non-diabetic mice

Polymeric scaffolds have been reported to promote angiogenesis, facilitating oxygen delivery; however, little is known about the effect of diabetes on the neo-vascularization of implanted polymeric scaffolds at subcutaneous (SC) sites. In this study we compare the effect of diabetes on scaffold vascularization following SC implantation into diabetic and non-diabetic mice. Wide pore agarose cryogel scaffolds with grafted gelatin were prepared by a two-step freezing procedure and subsequent thawing. The scaffolds were implanted subcutaneously into streptozoticin-induced diabetic mice and control, non-diabetic mice. The vascularization process was estimated using histological sections, in which endothelial cells were identified by Von Willebrand factor (vWF) and CD31 antigen staining and the pericyte layer was confirmed by α-smooth muscle actin (α-SMA) visualization. Comparative analysis showed a similar thickness of fibrous capsules around the vascularized scaffolds in both diabetic and non-diabetic animals. Intensive staining for α-SMA indicated the formation of mature blood vessels in the surrounding fibrous capsule and tissue invading the scaffold area. No statistically significant differences in capillary density and area occupied by blood vessels were found between diabetic and non-diabetic mice. In conclusion, the present study shows no adverse effects of diabetes on new blood vessel formation in SC implanted agarose cryogel scaffolds with grafted gelatin.

Evaluation of the effect of the degree of acetylation on the inflammatory response to 3D porous chitosan scaffolds

The effect of the degree of acetylation (DA) of 3D chitosan (Ch) scaffolds on the inflammatory reaction was investigated. Chitosan porous scaffolds with DAs of 4 and 15% were implanted using a subcutaneous air-pouch model of inflammation. The initial acute inflammatory response was evaluated 24 and 48 h after implantation. To characterize the initial response, the recruitment and adhesion of inflammatory cells to the implant site was studied. The fibrous capsule formation and the infiltration of inflammatory cells within the scaffolds were evaluated for longer implantation times (2 and 4 weeks). Chitosan with DA 15% attracted the highest number of leukocytes to the implant site. High numbers of adherent inflammatory cells were also observed in this material. For longer implantation periods Ch scaffolds with a DA of 15% induced the formation of a thick fibrous capsule and a high infiltration of inflammatory cells within the scaffold. Our results indicate that the biological response to implanted Ch scaffolds was influenced by the DA. Chitosan with a DA of 15% induce a more intense inflammatory response when compared with DA 4% Ch. Because inflammation and healing are interrelated, this result may provide clues for the relative importance of acetyl and amine functional groups in tissue repair and regeneration.

Hydrodynamic Parameters Modulate Biochemical, Histological, and Mechanical Properties of Engineered Cartilage

Functional engineered cartilage constructs represent a promising therapeutic approach for the replacement of damaged articular cartilage. The in vitro generation of cartilage tissue suitable for repair requires an understanding of the complex interrelationships between environmental cues, such as hydrodynamic forces, and tissue growth and development. In the present study, engineered cartilage constructs were cultivated in four well-defined hydrodynamic environments within a bioreactor, and correlations were established between construct ultrastructural and mechanical properties and key hydrodynamic parameters. Results suggest that even for similar composition, constructs may exhibit different mechanical properties due to differences in their ultrastructure that can be modulated by hydrodynamic parameters. For example, improved mechanical properties were observed in constructs that exhibited a thick fibrous outer capsule as a result of cultivation under increased hydrodynamic shear. In particular, uniformity in the contribution of the fluid velocity vectors (axial, radial, and tangential) to the total fluid velocity and shear stress were the hydrodynamic parameters that most affected the construct properties under investigation. The correlations identified here may be useful in the development of engineered tissue growth models that inform the design of bioreactor cultivation systems toward the production of clinically relevant engineered cartilage.

Pseudo tumours in haemophilia patients

Pseudo tumours are amongst the rare yet pathognomonic complications of haemophilia. They are old, encapsulated haematomas which due to their sometimes enormous size can cause massive complaints. These haematomas are surrounded by a thick fibrous capsule. They are attributed to persistent bleedings. The pathophysiology of pseudo tumors is not conclusively established yet. Some believe that they originate from bone material or the periosteum, while others suggest their development from soft tissue. They spread aggressively, displace the surrounding tissue, and cause secondary periosteal erosion of the bone. This results in bone resorption and destruction of surrounding muscular and soft tissue. Pseudo tumours develop slowly over many years. They occur primarily in adults and are largely unresponsive to conservative treatment. A 48-year-old man with moderate hemophiliaA (FVIII:C 2%) and no FVIII inhibitor. Due to recurrent bleeding into the muscle of the right thigh diagnosis of two pseudo tumours (psoas, adductor magnus). In 2004 tumour extirpation with subsequent relapse; because of high local bleeding tendency (despite permanent prophylaxis with FVIII concentrate and adjusted lifestyle) surgical revision in 02/2008. Postoperatively, no recurrent bleeding; the patient is fully fit for work three months later. In order to reduce the complication rate when a pseudo tumor is suspected, patients should be treated in a specially equipped interdisciplinary center with adequately trained and experienced surgeons and haemostaseologists.

Castleman′s disease: A rare diagnosis in retroperitoneum

Dear Sir,Castleman™s diseases is a rare benign disorder named after the pathologist who first described this clinical entity. We describe here a case of retroperitoneal peri-renal Castleman™s disease.A 22-year-old woman with no significant past medical history presented with complaints of epigastria discomfort and dull aching pain in right lumbar region for six months. Physical examination revealed a mass in right upper quadrant on deep palpation. Routine hematological profile and blood biochemistry were normal. Patient was HIV 1-2 negative. Chest and Abdominal roentgenograms were normal. Abdominal ultrasonography revealed a well-defined solid hypoechoic mass lesion 5 x 8 x 4.3 cm in size just inferior to level of head of pancreas anterior to inferior vena cava causing pressure effect on inferior vena cava.Vascularity was noted in the lesion on color Doppler study. Computed Tomography showed 5.5 x 4.8 x 4.6 cm well defined isodense mass lesion anterior to inferior vena cava in the region of uncinate process of pancreas causing pressure effect on inferior vena cava and left renal vein, uniformly enhancing on contrast study.Although a definitive pre-operative diagnosis could not be made surgical excision was planned. At laparotomy a 8 x 7.5 cm oval mass with thick fibrous capsule was found which was compressing inferior vena cava medially and renal vessels inferiorly. It was also pushing head of pancreas anteriorly, superiorly it was medial to adrenal gland and its capsule was adherent to the liver. Mass was excised

Expanded Polytetrafluoroethylene Membrane Alters Tissue Response to Implanted Ahmed Glaucoma Valve

Purpose: Long-term intraocular pressure control by glaucoma drainage implants is compromised by the formation of an avascular fibrous capsule that surrounds the glaucoma implant and increases aqueous outflow resistance. It is possible to alter this fibrotic tissue reaction and produce a more vascularized and potentially more permeable capsule around implanted devices by enclosing them in a porous membrane. Methods: Ahmed glaucoma implants modified with an outer 5-μ m pore size membrane (termed porous retrofitted implant with modified enclosure or PRIME-Ahmed) and unmodified glaucoma implants were implanted into paired rabbit eyes. After 6 weeks, the devices were explanted and subject to histological analysis. Results: A tissue response containing minimal vascularization, negligible immune response, and a thick fibrous capsule surrounded the unmodified Ahmed glaucoma implant. In comparison, the tissue response around the PRIME-Ahmed demonstrated a thinner fibrous capsule (46.4 ± 10.8 μ m for PRIME-Ahmed versus 94.9 ± 21.2 μ m for control, p < 0.001) and was highly vascularized near the tissue-material interface. A prominent chronic inflammatory response was noted as well. Conclusions: Encapsulating the aqueous outflow pathway with a porous membrane produces a more vascular tissue response and thinner fibrous capsule compared with a standard glaucoma implant plate. Enhanced vascularity and a thinner fibrous capsule may reduce aqueous outflow resistance and improve long-term glaucoma implant performance.

Interthalamic Hematoma Secondary to Cerebrovascular Atherosclerosis in an Aged Grizzly Bear (Ursus arctos horribilis) with Primary Cardiac Schwannoma

A 38-year-old intact female Grizzly bear (Ursus arctos horribilis) was evaluated for progressive seizure activity, pale mucous membranes, deficient pupillary light and menace responses, and irregular shallow respiration. Because of poor response to treatment, the animal was euthanized. Gross examination revealed abundant hemorrhage in both lateral ventricles; a large, encapsulated mass within the rostral interthalamic region; and a well-demarcated, round white mass in the apex of the right ventricle. Histologic examination of the interthalamic mass revealed a resolving hematoma composed of stratified layers of fibrin and white blood cells that was surrounded by a thick fibrous capsule. Most meningeal and intraparenchymal blood vessels had multifocal degeneration, fragmentation, and fraying of the internal elastic lamina with prominent intimal proliferations and plaques. The plaques were formed by small numbers of lipid-laden macrophages (foam cells) that were intermixed with occasional lymphocytes and plasma cells. The cardiac mass was composed of pallisading and interlacing spindle cells with parallel nuclei and abundant, pale eosinophilic cytoplasm consistent with a schwannoma.

Osteolysis of the radius and ulna induced by a circumferential foreign body in a cat

A 1-year-old neutered male cat was examined because of a 6-month history of recurrent swelling and draining wounds affecting the craniomedial aspect of the distal portion of the left forelimb. No lameness or neurologic deficits were evident. Examination of craniocaudal and lateromedial radiographic views revealed nonprogressive circumferential osteolysis and a mildly radiopaque, ring-shaped foreign body surrounding the radius and ulna. During surgery, a tight elastic band surrounded by a thick fibrous tissue capsule was found encircling the limb. Microbial culture yielded a Staphylococcus sp that was susceptible to clindamycin. Follow-up monitoring via telephone communication with the owners 1.5 years after removal of the foreign body indicated that the cat had healed with no recurrence of drainage. Pressure osteolysis of the bones of the forelimb can be caused by a circumferential foreign body without associated neurologic abnormalities or lameness.

Holostephanus metorchis (Digenea: Cyathocotylidae) from Chicks Experimentally Infected with Metacercariae from a Fish, Pseudorasbora parva, in the Republic of Korea

Holostephanus metorchis (Digenea: Cyathocotylidae) is a parasite of birds, transmitted by freshwater fishes. H. metorchis adults were recovered from chicks experimentally infected with metacercariae collected from freshwater fishes, Pseudorasbora parva. The metacercariae were oval, surrounded with thick fibrous capsules. In adult flukes, the holdfast organ occupied the ventral concavity, and the anterior testis did not reach the level of the ventral sucker. Based on these morphological characteristics, these flukes were identified as H. metorchis.

조직학과 효소활성 방법을 이용한 순 타이타늄과 타이타늄 합금의 상대적인 생체적합성 평가

Titanium or titanium alloy is a widely used implant material according to its certified biocompatibility, sufficient strength and ready availability. The purpose of this study was to evaluate the relative biocompatibility of titanium and titanium alloy specimens (Ti-29Nb-13Ta, TiNb and Ti-6Al-4V, Ti64) using in vivo and in vitro methods. For in vivo experiment, the specimens were implanted in the abdominal subcutaneous region of female mice for 2 and 4 weeks. The reaction of connective tissue to specimens was evaluated histologically. The specimens were encapsulated by fibrous connective tissue consisting of fibroblast, fibrocyte and other cells including neutrophil, macrophage, giant multinucleated cell and unidentified cells. Some newly formed blood vessels were located in the fibrous capsule surrounding the implant. Cell types and the thickness of fibrous capsules were examined quantitatively. Most of cell types located in the fibrous capsule were fibroblasts and fibrocytes. The average thickness of fibrous capsules for the TiNb specimens was much thinner than that of the titanium alloy, Ti64. The thickness of the fibrous capsule around all titanium specimens decreased at 4 weeks compared to 2 weeks post-implantation. The biocompatibility of titanium and titanium alloy specimens were also investigated in in vitro method using alkaline phosphatase from MG-63 cells. Alkaline phosphatase activity of the TiNb specimen showed higher activity than the titanium alloy, Ti64. In conclusion, the TiNb alloy with thin capsule thickness in vivo and high alkaline phosphatase activity in vitro will be of considerable use in biomedical applications.

Cystic endocrine tumor of the pancreas with an atypical multilocular appearance

A 46-year-old woman with epigastric pain was found to have a cystic tumor in the pancreas head on radiological examinations. The tumor was hypervascular, and its multilocular appearance resembled the "honeycomb" pattern of serous cystic tumor (SCT). The patient underwent surgery. The cut surface of the tumor showed a thick fibrous capsule with multiple cystic components, which contained necrotic tissue and brownish serous fluid, indicating an episode of hemorrhage. The cut surface of the tumor resembled solid-pseudopapillary tumor (SPT) on gross appearance. On immunohistochemical staining, the tumor cells showed diffuse and strong staining for synaptophysin (SYN), chromogranin A (CGA), and grimelius, and no staining for alpha 1-antitrypsin or CD10. We finally made a diagnosis of pancreatic endocrine tumor (PET). As PET sometimes shows an atypical multicystic appearance, immunohistochemical staining is mandatory for its correct diagnosis.

Análise comparativa entre esclera tratada com glicerina e esclera tratada com irradiação gama, álcali e glicerina em reconstrução de cavidade anoftálmica: estudo experimental em coelhos

To compare two sclera decontamination methods: treatment with glycerin versus treatment with gamma irradiation, alkali and glycerin, aiming to detect the clinical and histological alterations in rabbit anophthalmic sockets reconstructed with sclera-involved polymethylmethacrylate spheres. Thirty-nine New Zealand-breed rabbits were divided into two groups: group I, whose animals were submitted to enucleation of one eye and reconstruction with a polymethylmethacrylate sphere involved in glycerin-treated sclera; group II, where there was enucleation, and reconstruction performed with a polymethylmethacrylate sphere involved in sclera treated with gamma irradiation, alkali and glycerin. The two groups were observed at four moments, at 7, 21, 42 and 84 days after surgery. Preset times elapsed, the rabbits were euthanized, sockets were exenterated, the material was processed for embedment in paraffin, cut into 5 microm sections thick and stained with hematoxylin-eosin and Masson's trichrome techniques. The scleras were submitted to morphometric and semiquantitative analysis. Results were compared by Mann-Whitney's non-parametric test. Comparative analysis of vascularization of the surgical interface pointed out a significative difference in the evaluation done 21 days after the implant (P<0.001), with group II showing greater neovascularization. Comparison of the fibrous capsule thickness displayed a significative difference at moments corresponding to 21 days (P<0.001) and 42 days (P<0.001). At both moments, group II presented a thicker fibrous capsule than group I. Likewise, there was variation in sclera thickness, being thicker in group II, at the 21-day post-implant (P=0.003) moment, and at the 42-day moment (P=0.024), as well. Along the experimental period, when groups were analyzed we could observe statistically significative diminution of vascularization in the surgical interface, in group I, as well as in group II, at the moment of 7, 21, 42 and 84 days. When used as coating on the polymethylmethacrylate implant for the reconstruction of rabbit anophthalmic socket, the sclera treated with gamma irradiation, alkali and glycerin reacted similarly to the traditionally used glycerin-treated sclera. The two treatments induced a similar inflammatory response. The formation of neovessels, thickness of fibrous capsule and of sclera developed differently in the two groups. Nevertheless, they presented similar results at the end of the 84-day observation period. There was no significant difference between the two groups, with regard to sclera preservation.

Merkel Cell-Poor Trichoblastoma With Basal Cell Carcinoma-Like Foci

We reexamined 11 cases of trichoblastoma, and two cases of trichoblastoma with basal cell carcinoma (BCC)-like foci were found. In these two trichoblastomas with BCC-like foci, the BCC-like foci were often localized in peripheral or deep areas of lesions extending out of the fibrocytic stroma. Immunohistochemistry was performed in five conventional trichoblastomas and in two trichoblastomas with BCC-like foci, using antibodies against CK20 and CK15. No CK20-positive Merkel cells and no expression of CK15 were seen in any neoplastic aggregations of the two trichoblastomas with BCC-like foci. In contrast, increased numbers of Merkel cells and positive staining for CK15 were observed in all five trichoblastomas without BCC-like foci. The five trichoblastomas without BCC-like foci included two trichoblastomas with a popped out or shelled out appearance, which characteristically had a thick fibrous capsule surrounding the fibrotic stroma, demonstrating numerous Merkel cells in the aggregations. Some trichoblastomas may undergo mutations, resulting in the development of foci of BCC and in the loss of the expression of CK15 as well as the disappearance of Merkel cells.

P62: Ultrasound guidance for the difficult lap band adjustment

As experience with the LapBand system increases, it is apparent that many practitioners perform postoperative adjustments in the office setting using simple palpation to access the port. In most cases this is adequate and saves much time and effort in scheduling for radiographic assistance and time, etc.. There are certain instances, however, where the port is difficult to palpate or access due to an inordinately thick abdominal wall, thick fibrous capsule formation, or in cases of suspected port migration or rotation.