Neuronal functional connectivity is impaired in a layer dependent manner near chronically implanted intracortical microelectrodes in C57BL6 wildtype mice.

Objective.This study aims to reveal longitudinal changes in functional network connectivity within and across different brain structures near chronically implanted microelectrodes. While it is well established that the foreign-body response (FBR) contributes to the gradual decline of the signals recorded from brain implants over time, how the FBR affects the functional stability of neural circuits near implanted brain-computer interfaces (BCIs) remains unknown. This research aims to illuminate how the chronic FBR can alter local neural circuit function and the implications for BCI decoders.Approach.This study utilized single-shank, 16-channel,100µm site-spacing Michigan-style microelectrodes (3 mm length, 703µm2 site area) that span all cortical layers and the hippocampal CA1 region. Sex balanced C57BL6 wildtype mice (11-13 weeks old) received perpendicularly implanted microelectrode in left primary visual cortex. Electrophysiological recordings were performed during both spontaneous activity and visual sensory stimulation. Alterations in neuronal activity near the microelectrode were tested assessing cross-frequency synchronization of local field potential (LFP) and spike entrainment to LFP oscillatory activity throughout 16 weeks after microelectrode implantation.Main results. The study found that cortical layer 4, the input-receiving layer, maintained activity over the implantation time. However, layers 2/3 rapidly experienced severe impairment, leading to a loss of proper intralaminar connectivity in the downstream output layers 5/6. Furthermore, the impairment of interlaminar connectivity near the microelectrode was unidirectional, showing decreased connectivity from Layers 2/3 to Layers 5/6 but not the reverse direction. In the hippocampus, CA1 neurons gradually became unable to properly entrain to the surrounding LFP oscillations.Significance. This study provides a detailed characterization of network connectivity dysfunction over long-term microelectrode implantation periods. This new knowledge could contribute to the development of targeted therapeutic strategies aimed at improving the health of the tissue surrounding brain implants and potentially inform engineering of adaptive decoders as the FBR progresses. Our study's understanding of the dynamic changes in the functional network over time opens the door to developing interventions for improving the long-term stability and performance of intracortical microelectrodes.

[Silver Ion Decreases Foreign Body Reaction and Venous Neointimal Hyperplasia through the Inhibition of Interleukin-33 Expression].

INTRODUCTION: Vascular prosthetic grafts are widely used in vascular surgery; however, graft infection remains a major concern. Silver-coated vascular grafts have demonstrated anti-infection properties in clinical settings; however, whether the silver irons influence foreign body reaction or neointimal hyperplasia remains unclear. METHODS: Sodium alginate and hyaluronic acid (SA/HA) hydrogel patches loaded with rhodamine, with or without silver, were fabricated. Patches were implanted in the subcutaneous or abdominal cavity and inferior vena cava of rats. Samples were harvested on day 14 and examined via immunohistochemical and immunofluorescence analyses. RESULTS: Silver hydrogel was found to decrease the foreign body reaction; after subcutaneous and abdominal cavity implantation in rats, the capsule was found to be thinner in the silver hydrogel group than in the control hydrogel group. The silver hydrogel group had fewer CD68-positive cells and proliferating cell nuclear antigen and interleukin-33 (IL-33) dual-positive cells than the control hydrogel group. Additionally, the silver hydrogel patch reduced the neointimal thickness after patch venoplasty in rats, and the number of IL-33- and IL-1ß-positive cells was lower than that in the control patch. CONCLUSION: Silver-loaded SA/HA hydrogel patches decreased the foreign body reaction and venous neointimal hyperplasia in rats by the inhibition of IL-33 expression.

Omental coating attenuates implant-induced foreign body reaction in rats.

The objective of this study is to clarify whether the omental coating can effectively attenuate foreign body reaction (FBR) induced by implanted materials. Male Sprague-Dawley rats were injected with polydextran particle slurry intraperitoneally to activate the omentum. 7 days later, polyether polyurethane sponge discs were implanted subcutaneously on each side of the rat's back as the foreign implants to induce FBR. The next day, omental transposition were performed. The disc on the left side of each rat's back was wrapped with omental flap (omental group); the disc on the right side was untreated (control group). All discs were removed 21 days after implantation and assessed by determining the components of the fibrovascular tissue (angiogenesis, inflammation, foreign body giant cells (FBGCs) aggregation and fibrogenesis). In implants in omental group, micro vessel density (MVD), Hemoglobin (Hb) content and VEGF levels (pro-angiogenic cytokine) were increased when compared with implants from control group. Inflammatory parameters (IL-1ß; macrophage accumulation-NAG activity; neutrophil accumulation- MPO levels) were decreased in implants after omental coating. Also, collagen deposition, fibrous capsule thickness, and FBGCs decreased in implants from omental group. However, intra-implant levels of TNF-α and TGF-ß1 were not different after omental coating. Our findings showed for the first time that the omental coating around the implants attenuate the adverse FBR, it may be critical in developing new strategies to control FBR and improve the function and performance of the implanted materials.

Decoding the "Fingerprint" of Implant Materials: Insights into the Foreign Body Reaction.

Foreign body reaction (FBR) is a prevalent yet often overlooked pathological phenomenon, particularly within the field of biomedical implantation. The presence of FBR poses a heavy burden on both the medical and socioeconomic systems. This review seeks to elucidate the protein "fingerprint" of implant materials, which is generated by the physiochemical properties of the implant materials themselves. In this review, the activity of macrophages, the formation of foreign body giant cells (FBGCs), and the development of fibrosis capsules in the context of FBR are introduced. Additionally, the relationship between various implant materials and FBR is elucidated in detail, as is an overview of the existing approaches and technologies employed to alleviate FBR. Finally, the significance of implant components (metallic materials and non-metallic materials), surface CHEMISTRY (charge and wettability), and physical characteristics (topography, roughness, and stiffness) in establishing the protein "fingerprint" of implant materials is also well documented. In conclusion, this review aims to emphasize the importance of FBR on implant materials and provides the current perspectives and approaches in developing implant materials with anti-FBR properties.

Foreign Body Reaction Mimicking Lymph Node Metastasis is Not Rare After Lung Cancer Resection.

BACKGROUND: Mediastinal lymphadenopathies with high 18-fluorodeoxyglucose uptake in patients previously operated on for lung cancer are alarming for recurrence and necessitate invasive diagnostic procedures. Peroperative placement of oxidized cellulose to control minor bleeding may lead to a metastasis-like image through a foreign body reaction within the dissected mediastinal lymph node field at postoperative examinations. In this study, we investigated clinicopathological features and the frequency of foreign body reaction mimicking mediastinal lymph node metastasis. METHODS: Patients who underwent surgery for lung cancer between January 2016 and August 2021 and who were subsequently evaluated for mediastinal recurrence with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) were included. Patients were grouped according to the results of EBUS-TBNA as metastasis, foreign body, and reactive. Clinicopathological features of these patients were compared and characteristics of patients in the foreign body group were scrutinized. RESULTS: EBUS-TBNA was performed on a total of 34 patients during their postoperative follow-up due to suspicion of mediastinal recurrence. EBUS-TBNA pathological workup revealed metastasis in 18 (52.9%), foreign body reaction in 10 (29.4%) and reactive lymph nodes in 6 (17.6%) patients. Mean maximum standardized uptake value (SUVMax) for metastasis group and foreign body group were 9.39 ± 4.69 and 5.48 ± 2.54, respectively (p = 0.022). Time interval between the operation and EBUS-TBNA for the metastasis group was 23.72 ± 10.48 months, while it was 14.90 ± 12.51 months in the foreign body group (p = 0.015). CONCLUSION: Foreign body reaction mimicking mediastinal lymph node metastasis is not uncommon. Iatrogenic cause of mediastinal lymphadenopathy is related to earlier presentation and lower SUVMax compared with metastatic lymphadenopathy.

Editorial Commentary: A Biphasic (Calcified and Demineralized), Cancellous, Interpositional Allograft Augmenting Rotator Cuff Repair in an Ovine Model Does Not Show Harmful Inflammation or Foreign Body Reaction.

To improve the outcomes of arthroscopic rotator cuff (RC) repair, it is important to achieve tendon-to-bone healing at the repair site. Healed repairs are more likely to restore shoulder strength and lead to higher magnitudes of satisfaction. Patches or grafts that can be either secured to the bursal surface of the RC or interposed between the RC tendon and greater tuberosity at the time of repair have been described as adjuncts to RC repair. A cancellous, biphasic allograft tissue composed of 2 layers (calcified to promote osseointegration and demineralized to support soft-tissue ingrowth) has been shown to be safe in an ovine model, without a harmful inflammatory or foreign body response. Human trials may be a reasonable next step.

Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response.

Biomedical devices comprise a major component of modern medicine, however immune-mediated fibrosis and rejection can limit their function over time. Here, we describe a humanized mouse model that recapitulates fibrosis following biomaterial implantation. Cellular and cytokine responses to multiple biomaterials were evaluated across different implant sites. Human innate immune macrophages were verified as essential to biomaterial rejection in this model and were capable of cross-talk with mouse fibroblasts for collagen matrix deposition. Cytokine and cytokine receptor array analysis confirmed core signaling in the fibrotic cascade. Foreign body giant cell formation, often unobserved in mice, was also prominent. Last, high-resolution microscopy coupled with multiplexed antibody capture digital profiling analysis supplied spatial resolution of rejection responses. This model enables the study of human immune cell-mediated fibrosis and interactions with implanted biomaterials and devices.

Breast filler granuloma mistaken for implant rupture: A case report.

RATIONALE: Breast augmentation is usually performed by inserting implants into the breasts. However, injectable fillers are sometimes used for the convenience of both patients and surgeons. If foreign substances, such as biomaterials, are injected into the body, complications such as inflammation, granuloma, and tissue necrosis can occur owing to foreign body reactions. PATIENT CONCERNS: A 39-year-old female patient visited our hospital complaining of tenderness, redness, and swelling in both breasts. The patient had undergone bilateral breast augmentation using implants 4 years prior to current consult. DIAGNOSES: On magnetic resonance imaging (MRI), cystic lesions and fluid collections were observed, with findings suggesting implant rupture; hence, surgery was planned to remove both implants. INTERVENTIONS: Intraoperatively, the implant was malpositioned in the upper lateral portion without rupture. Capsular contracture findings were also not prominent. A large amount of inflammatory granuloma was observed and removed in the prepectoral plane, and the implants were immediately inserted into a new subpectoral plane. OUTCOMES: The volume of the new implant was 175 mL, which was smaller than the previous one, as per the patient preference. Cytology of the fluid from the previous implant pocket showed no evidence of malignancy, and the granuloma was identified as inflammatory tissue caused by a foreign body reaction on biopsy. The excessive protrusion of both breasts was corrected after surgery, and the patient was satisfied with the aesthetic outcomes without any complications up to 3 months after surgery. LESSONS: The use of injectable fillers for breast augmentation carries the risk of misdiagnosis, and, therefore, surgeons should always exercise caution.

Polymethylmethacrylate-induced foreign body reaction presenting as bilateral parotid lesions: A case report of dermal filler adverse reaction diagnosed on fine needle aspiration.

BACKGROUND: Dermal filler injections are being increasingly used as a non-surgical option for facial cosmetic procedures. However, their use has been implicated in multiple adverse events including immediate, early onset, and late onset complications. AIM: We present a case of dermal filler-induced foreign body reaction presenting as bilateral parotid lesions and diagnosed using fine needle aspiration. CONCLUSION: This case elucidate the risk of delayed adverse events in patients with dermal filler injections and stresses the importance of awareness by patients and providers for such events.

Oral formulation of Wnt inhibitor complex reduces inflammation and fibrosis in intraperitoneal implants in vivo.

The use of implantable biomaterials to replace physiological and anatomical functions has been widely investigated in the clinic. However, the selection of biomaterials is crucial for long-term function, and the implantation of certain biomaterials can cause inflammatory and fibrotic processes, triggering a foreign body reaction that leads to loss of function and consequent need for removal. Specifically, the Wnt signaling pathway controls the healing process of the human body, and its dysregulation can result in inflammation and fibrosis, such as in peritoneal fibrosis. Here, we assessed the effects of daily oral administration of a Wnt pathway inhibitor complex (CD:LGK974) to reduce the inflammatory, fibrotic, and angiogenic processes caused by intraperitoneal implants. CD:LGK974 significantly reduced the infiltration of immune cells and release of inflammatory cytokines in the implant region compared to the control groups. Furthermore, CD:LGK974 inhibited collagen deposition and reduced the expression of pro-fibrotic α-SMA and TGF-ß1, confirming fibrosis reduction. Finally, the CD:LGK974 complex decreased VEGF levels and both the number and area of blood vessels formed, suggesting decreased angiogenesis. This work introduces a potential new application of the Wnt inhibitor complex to reduce peritoneal fibrosis and the rejection of implants at the intraperitoneal site, possibly allowing for longer-term functionality of existing clinical biomaterials.

Extensive Foreign Body Reaction to Synthetic Dural Replacement After Decompressive Craniectomy with Radiological and Histopathology Evidence: Observational Case Series.

BACKGROUND: Though the indications are quite varied, decompressive craniectomy is considered a life-saving procedure. Maximal effectiveness of craniectomy is achieved when, in addition to bone removal, the dura mater is opened properly and is augmented with duraplasty. Different synthetic materials have been used over the decades to replace the dura during decompressive craniectomy. We have used different synthetic dural replacements at our institution, including Neuro-Patch, DuraGen, and Lyoplant. In this case series, we described 4 cases that had excessive granulation tissue formation in response to a newly used synthetic dural substitute (ReDura) after emergent decompressive craniectomy. During follow-up brain imaging at different intervals, these cases were found to have foreign body reaction in the form of excessive granulation tissue formation; additionally, 1 case had a sterile pus-like collection. The granulation tissue diagnosis was affirmed by histopathology in all 4 cases. METHODS: This study was an observational retrograde case series, with data obtained from electronic medical records. RESULTS: The study showed extensive foreign body giant cell reactions on preoperative computed tomography scans, indicating a very high occurrence rate of 72.4%, when ReDura was used as dural replacement. CONCLUSIONS: Our experience showed that patients are prone to develop severe foreign body giant cell reactions with ReDura. Neurosurgical centers using this material should monitor patients for possible abnormal foreign body reaction and report it to establish the safety and efficacy profile of this material.

Infraorbital mass long after dermal filler injection: A report of two cases.

BACKGROUND: Hyaluronic acid fillers have been increasingly used throughout the world in the management of aging skin in the periocular region and other areas. OBJECTIVE: To evaluate very late-term orbital mass formation secondary to Hyaluronic acid filler injection into the inferior eyelid. METHODS: We report two cases that presented with a subcutaneous palpable mass localized at the right medial lower infraorbital area. Following clinical and radiological examination, surgical excision was required for the differential diagnosis of tumor. RESULTS: After pathologic examination and the finding of a foreign-body granulomatous reaction, both patients recalled that hyaluronic acid filler had once been injected into their lower eyelids approximately 10 years prior. This is consistent with the fact that dermal-filler-related granuloma formation may occur even years later in the differential diagnosis of mass lesions. CONCLUSION: It is suggested that patients be informed about the possible but rare mass effect in the infraorbital region. Clinicians should also attend to delayed hypersensitivity reactions, since patients may not recall details due to the length of time since injection.

Exploring the Overlooked Roles and Mechanisms of Fibroblasts in the Foreign Body Response.

Significance: Foreign body response (FBR), wherein a fibrotic capsule forms around an implanted structure, is a common surgical complication that often leads to pain, discomfort, and eventual revision surgeries. Although believed to have some mechanistic overlap with normal wound healing, much remains to be discovered about the specific mechanism by which this occurs. Recent Advances: Current understanding of FBR has focused on the roles of the immune system and the biomaterial, both major contributors to FBR. However, another key player, the fibroblast, is often overlooked. This review summarizes key contributors of FBR, focusing on the roles of fibroblasts. As much remains to be discovered about fibroblasts' specific roles in FBR, we draw on current knowledge of fibroblast subpopulations and functions during wound healing. We also provide an overview on candidate biomaterials and signaling pathways involved in FBR. Critical Issues and Future Directions: While the global implantable medical devices market is considerable and continues to appreciate in value, FBR remains one of the most common surgical implant complications. In parallel with the continued development of candidate biomaterials, further exploration of potential fibroblast subpopulations at a transcriptional level would provide key insights into further understanding the underlying mechanisms by which fibrous encapsulation occurs, and unveil novel directions for antifibrotic and regenerative therapies in the future.

Novel management of granuloma formation secondary to dermal filler: A multi-modality approach.

BACKGROUND: Dermal fillers for soft tissue augmentation have become increasingly popular among patients of all ages and ethnicities. With more widespread use, there has been an increased incidence of adverse reactions, one of which is the granulomatous foreign body reaction (GFBR). MATERIALS & METHODS: We present a three patient case series in which GFBR secondary to dermal filler was successfully treated with a multi-leveled approach. The first modality involves intralesional injection of a mixture containing 1 cc of 5-fluorouracil (5-FU), 0.5 cc of dexamethasone sodium phosphate, and 0.1 cc of triamcinolone 10. The lesion is injected intradermally in small aliquots, similar to scar treatment. The patient then takes colchicine 1.2 mg loading dose on day 1, then 0.6 mg twice per day for 4 days concurrently with naproxen 500 mg orally once daily for 5-7 days. This process may be repeated in 6 weeks if the lesions have not resolved and PDL laser may be employed for residual post-inflammatory erythema. RESULTS: All three patients presented in this case series had significant aesthetic improvement in their dermal filler-derived foreign body granulomatous reactions. CONCLUSION: GFBR provides both a medical and aesthetic issue for these patients including mental distress, pain, and dysfunction, therefore having an effective treatment for GFBR will affect medical management of these patients, improving patient outcomes and satisfaction. Our proposed regimen for GFBR has been shown to be highly efficacious and safe for these patients, providing a significant improvement in both function and cosmesis of the area.

Biomaterial Design Inspired by Regenerative Research Organisms.

The efficacy of implanted biomaterials is largely dependent on the response of the host's immune and stromal cells. Severe foreign body response (FBR) can impede the integration of the implant into the host tissue and compromise the intended mechanical and biochemical function. Many features of FBR, including late-stage fibrotic encapsulation of implants, parallel the formation of fibrotic scar tissue after tissue injury. Regenerative organisms like zebrafish and salamanders can avoid fibrosis after injury entirely, but FBR in these research organisms is rarely investigated because their immune competence is much lower than humans. The recent characterization of a regenerative mammal, the spiny mouse (Acomys), has inspired us to take a closer look at cellular regulation in regenerative organisms across the animal kingdom for insights into avoiding FBR in humans. Here, we highlight how major features of regeneration, such as blastema formation, macrophage polarization, and matrix composition, can be modulated across a range of regenerative research organisms to elucidate common features that may be harnessed to minimize FBR. Leveraging a deeper understanding of regenerative biology for biomaterial design may help to reduce FBR and improve device integration and performance.

Massive foreign body reaction and osteolysis following primary anterior cruciate ligament reconstruction with the ligament augmentation and reconstruction system (LARS): a case report with histopathological and physicochemical analysis.

BACKGROUND: Autologous hamstrings and patellar tendon have historically been considered the gold standard grafts for anterior cruciate ligament reconstruction (ACLR). In the last decades, the utilization of synthetic grafts has re-emerged due to advantageous lack of donor site morbidity and more rapid return to sport. The Ligament Augmentation and Reconstruction System (LARS) has demonstrated to be a valid and safe option for ACLR in the short term. However, recent studies have pointed out the notable frequency of associated complications, including synovitis, mechanical failure, and even chondrolysis requiring joint replacement. CASE PRESENTATION: We report the case of a 23-year-old male who developed a serious foreign body reaction with wide osteolysis of both femoral and tibial tunnels following ACLR with LARS. During first-stage arthroscopy, we performed a debridement of the pseudocystic mass incorporating the anterior cruciate ligament (ACL) and extending towards the tunnels, which were filled with autologous anterior iliac crest bone graft chips. Histological analysis revealed the presence of chronic inflammation, fibrosis, and foreign body giant cells with synthetic fiber inclusions. Furthermore, physicochemical analysis showed signs of fiber depolymerization, increased crystallinity and formation of lipid peroxidation-derived aldehydes, which indicate mechanical aging and instability of the graft. After 8 months, revision surgery was performed and ACL revision surgery with autologous hamstrings was successfully carried out. CONCLUSIONS: The use of the LARS grafts for ACLR should be cautiously contemplated considering the high risk of complications and early failure.

Clinical Features and Treatment of Intra-Tendinous Suture Reaction Following Achilles Tendon Repair Using Nonabsorbable Suture Material: A Retrospective Case Series Study.

We aimed to investigate the clinical manifestations, radiological findings, and therapeutic outcome of treatment for patients with surgically confirmed foreign body reaction following an Achilles tendon repair using non-absorbable suture material. Eight consecutive patients who were confirmed as having an intra-tendinous suture foreign body reaction in the histopathological report were enrolled in this study. Medical records of all patients in terms of clinical and radiological features were retrieved. Also, the outcome of treatment was evaluated at a follow-up of at least 12 months. All the patients complained of pain and a palpable mass around a previous surgical site at mean 25.1 months (range, 4-72 months) after the initial surgery. Magnetic resonance imaging (MRI) or ultrasound were used to detect the lesion. All the patients underwent surgical excision of foreign body reaction tissue and primary repair using absorbable suture material. After the treatment, the wounds were healed completely in all, and the average FAOS (foot and ankle outcome score) was 91.32 at mean follow-up for 22.4 months. In conclusion, intra-tendinous suture reaction is a rare complication following an Achilles tendon repair using nonabsorbable suture material, but it can be treated adequately with only surgical excision of foreign body reaction tissue and primary repair using absorbable suture material.