Silicone Implants Immobilized with Interleukin-4 Promote the M2 Polarization of Macrophages and Inhibit the Formation of Fibrous Capsules

Breast augmentations with silicone implants can have adverse effects on tissues that, in turn, lead to capsular contracture (CC). One of the potential ways of overcoming CC is to control the implant/host interaction using immunomodulatory agents. Recently, a high ratio of anti-inflammatory (M2) macrophages to pro-inflammatory (M1) macrophages has been reported to be an effective tissue regeneration approach at the implant site. In this study, a biofunctionalized implant was coated with interleukin (IL)-4 to inhibit an adverse immune reaction and promoted tissue regeneration by promoting polarization of macrophages into the M2 pro-healing phenotype in the long term. Surface wettability, nitrogen content, and atomic force microscopy data clearly showed the successful immobilization of IL-4 on the silicone implant. Furthermore, in vitro results revealed that IL-4-coated implants were able to decrease the secretion of inflammatory cytokines (IL-6 and tumor necrosis factor-α) and induced the production of IL-10 and the upregulation of arginase-1 (mannose receptor expressed by M2 macrophage). The efficacy of this immunomodulatory implant was further demonstrated in an in vivo rat model. The animal study showed that the presence of IL-4 diminished the capsule thickness, the amount of collagen, tissue inflammation, and the infiltration of fibroblasts and myofibroblasts. These results suggest that macrophage phenotype modulation can effectively reduce inflammation and fibrous CC on a silicone implant conjugated with IL-4.

Hyperactivation of RAP1 and JAK/STAT Signaling Pathways Contributes to Fibrosis during the Formation of Nasal Capsular Contraction

Silicone implant-based augmentation rhinoplasty or mammoplasty induces capsular contracture, which has been acknowledged as a process that develops an abnormal fibrotic capsule associated with the immune response to allogeneic materials. However, the signaling pathways leading to the nasal fibrosis remain poorly investigated. We aimed to explore the molecular mechanism underlying the pathogenesis of nasal capsular contracture, with a specific research interest in the signaling pathways involved in fibrotic development at the advanced stage of contracture. By examining our recently obtained RNA sequencing data and global gene expression profiling between grade II and grade IV nasal capsular tissues, we found that both the RAP1 and JAK/STAT signaling pathways were hyperactive in the contracted capsules. This was verified on quantitative real-time PCR which demonstrated upregulation of most of the representative component signatures in these pathways. Loss-of-function assays through siRNA-mediated Rap1 silencing and/or small molecule-directed inhibition of JAK/STAT pathway in ex vivo primary nasal fibroblasts caused a series of dramatic behavioral and functional changes, including decreased cell viability, increased apoptosis, reduced secretion of proinflammatory cytokines, and synthesis of type I collagen, compared to control cells, and indicating the essential role of the RAP1 and JAK/STAT signaling pathways in nasal capsular fibrosis. Our results sheds light on targeting downstream signaling pathways for the prevention and therapy of silicone implant-induced nasal capsular contracture.

INFECTED SILICONE CHIN IMPLANT AFTER IMPLANT-SUPPORTED JAW REHABILITATION: CASE REPORT AND LITERATURE REVIEW

To report the infected silicone chin implant due to the non-ideal placement of dental implants, in female patient, 67 years old. A patient unsatisfied with her facial profile had installed a silicone chin implant 25 years ago. Recently underwent surgery for the placement of dental implants in a region close to the silicone implant. The non-ideal positioning of the dental implants and close contact with the silicone implant led to the absence of osseointegration, with consequent mobility and infection of both. The silicone implant was removed with dental implant that shows mobility. In the imaging exams could be noted others complications of silicone implant like bone resorption and the formation of a narrow bone layer around the inferior border of implant. Alloplastic implants are an option for the esthetic correction of chin deformities. Solid silicone is biocompatible and highly resistant to degradation, with a minimal allergic reaction and risk of toxicity. However, a number of postoperative complications may arise, such as migration or displacement, extrusion, foreign body reaction, bone resorption, heterotopic bone formation and infection. The precise imaging exams are critical to arrive at a diagnosis and the best treatment plan.

In vivo assessment of the biocompatible properties of resorbable porous materials for pleural implantation

Correcting the pleural cavity space or filling large residual cavities (up to 500-700 cm3), arising as a result of extensive combined resections of the lung or extrapleural pneumolysis in tuberculosis and other lung diseases, still remains a challenging issue. The surgical methods used to correct the pleural cavity space are traumatic in nature. Moreover, various biological and synthetic materials used are not effective enough. Objective: to conduct an in vivo study of the biocompatible properties of laboratory samples of porous materials based on polylactide (PLA) and polycaprolactone (PCL) as potential materials for pleural implants development, as part of the general problem of developing a resorbable porous implant for intra- and extrapleural implantation and in situ formation of a «biological filling» to correct the volume of the pleural cavity. Materials and methods. In vivo subcutaneous implantation was performed in Wistar rats. The experiment involved the following samples: No. 1 - 3.0%; No. 2 - 4.0%; No. 3 - 1.7%. The ratio of the polymers in the solution was, respectively: 3/1, 1/3 and 1/1 PLA/PCL. Highly porous implants were obtained by lyophilization. The porosity of the samples ranged from 96.0% to 98.3%. The Young's modulus was from 100 to 1800 kPa. In the control group, a Mentor silicone implant shell was used. The explantation time was 1, 2, 3, 4, 5, 8, 12, 14 weeks. Histological, histochemical and immunohistochemical studies of explants and surrounding local tissues were conducted. Results. Reaction of local tissues to the implantation of three types of samples of different composition from PLA/PCL, accompanied by material resorption processes, replacement by fibrous tissue, vascularization and encapsulation, without perifocal inflammation and reactive changes, indicates the biocompatibility of the materials studied. In control samples with silicone implant, a long-lasting perifocal reaction from eosinophilic leukocytes was revealed, which prevents us from excluding the possibility of an allergic reaction to the implant material in the surrounding tissues. Conclusion. In vivo experiments on the small animals show the biosafety and high biocompatibility of laboratory samples of bioresorbable highly porous matrices based on polylactide and polycaprolatcon as potential materials for development of pleural implants. Further studies with scaling of laboratory samples and a detailed study of the dynamics of biodegradation of porous matrices in vivo in large animals are required. The need for further improvement in laboratory samples of bioresorbable pleural implants is associated with giving the porous matrices antibacterial, bioactive and X-ray contrast properties.