Utilization of a highly adaptable murine air pouch model for minimally invasive testing of the inflammatory potential of biomaterials.

Introduction: The biocompatibility of an implanted material strongly determines the subsequent host immune response. After insertion into the body, each medical device causes tissue reactions. How intense and long-lasting these are is defined by the material properties. The so-called foreign body reaction is a reaction leading to the inflammation and wound healing process after implantation. The constantly expanding field of implant technology and the growing areas of application make optimization and adaptation of the materials used inevitable. Methods: In this study, modified liquid silicone rubber (LSR) and two of the most commonly used thermoplastic polyurethanes (TPU) were compared in terms of induced inflammatory response in the body. We evaluated the production of inflammatory cytokines, infiltration of inflammatory cells and encapsulation of foreign bodies in a subcutaneous air-pouch model in mice. In this model, the material is applied in a minimally invasive procedure via a cannula and in one piece, which allows material testing without destroying or crushing the material and thus studying an intact implant surface. The study design includes short-term (6 h) and long-term (10 days) analysis of the host response to the implanted materials. Air-pouch-infiltrating cells were determined by flow cytometry after 6 h and 10 days. Inflammation, fibrosis and angiogenesis markers were analyzed in the capsular tissue by qPCR after 10 days. Results: The foreign body reaction was investigated by macroscopic evaluation and scanning electron microscopy (SEM). Increased leukocyte infiltration was observed in the air-pouch after 6 h, but it markedly diminished after 10 days. After 10 days, capsule formations were observed around the materials without visible inflammatory cells. Discussion: For biocompatibility testing materials are often implanted in muscle tissue. These test methods are not sufficiently conclusive, especially for materials that are intended to come into contact with blood. Our study primarily shows that the presented model is a highly adaptable and minimally invasive test system to test the inflammatory potential of and foreign body reaction to candidate materials and offers more precise analysis options by means of flow cytometry.

Altered Foreign Body Response at the Posterior Surface Compared to the Anterior Surface of Human Silicone Breast Implants.

Soft implantable devices are crucial to optimizing form and function for many patients. However, periprosthetic capsule fibrosis is one of the major challenges limiting the use of implants. Currently, little is understood about how spatial and temporal factors influence capsule physiology and how the local capsule environment affects the implant structure. In this work, we analyzed breast implant capsule specimens with staining, immunohistochemistry, and real-time polymerase chain reaction to investigate spatiotemporal differences in inflammation and fibrosis. We demonstrated that in comparison to the anterior capsule against the convex surface of breast implants, the posterior capsule against the flat surface of the breast implant displays several features of a dysregulated foreign body reaction including increased capsule thickness, abnormal extracellular remodeling, and infiltration of macrophages. Furthermore, the expression of pro-inflammatory cytokines increased in the posterior capsule across the lifespan of the device, but not in the anterior capsule. We also analyzed the surface oxidation of breast explant samples with XPS analysis. No significant differences in surface oxidation were identified either spatially or temporally. Collectively, our results support spatiotemporal heterogeneity in inflammation and fibrosis within the breast implant capsule. These findings presented here provide a more detailed picture of the complexity of the foreign body reaction surrounding implants destined for human use and could lead to key research avenues and clinical applications to treat periprosthetic fibrosis and improve device longevity.

Delayed orbital floor implant complications: Case report and review of the literature.

Purpose: Foreign body reaction to non-absorbable alloplastic orbital implants utilized for bony reconstruction are infrequently documented in the literature. We present the workup and surgical management of a giant cystic mass encapsulating a patient's alloplastic orbital implant, which was ultimately deemed to be a result of foreign body reaction. Observations: A 41-year-old male patient with distant history of a right orbital floor fracture had undergone repair with the placement of a nylon foil implant. The patient presented twenty years later with progressive ipsilateral globe proptosis and was found to have a giant inferior orbital cyst. Surgical exploration and removal of the implant and capsule were performed. Histopathology confirmed a delayed foreign body reaction around the patient's alloplastic implant. Conclusions: Alloplastic implants may result foreign body reaction and cyst encapsulation as a delayed complication.

Histological Evaluation of Alveolar Ridge Preservation Using Different Bone Grafts: Clinical Study Analysis Part II.

OBJECTIVE: To compare histologically the percentage of bone formation 12-20 weeks post-ridge augmentation using two different techniques. BACKGROUND: Tooth loss is associated with three-dimensional bone remodeling and ridge atrophy. Ridge preservation procedures can prevent alveolar bone volume loss. Different techniques and materials are used to preserve the alveolar ridge. MATERIALS & METHODS: Computer-generated randomization software was used to assign two ridge preservation techniques for 11 extraction sites. In group I (type I bovine Achilles tendon collagen plugs with bioactive resorbable calcium apatite crystals (CPCAC) and ingroup II, cortico-cancellous bone chips (CCBC) mix, and an expanded polytetrafluoroethylene (ePTFE) barrier membrane were placed. The histomorphometric studies were performed using a computer-based image analysis system (IMAGE-J 1.4, National Institute of Health, Bethesda, MD, USA) to calculate the pixel area of bone tissue and the remaining bone graft material. The histomorphometric data were analyzed using a Student's t-test to compare the measurements between the two experimental groups. This parametric statistical test was employed to determine if there were any statistically significant differences in the quantitative histological parameters between the groups. Results: The sockets that received CPCAC showed a lower (31.89%) percentage of native bone surface area compared to the CCBC group (43.87%). However, the difference was not statistically significant (P< 0.05). In addition, group CPCAC showed evidence of foreign body reaction. CONCLUSION: The CCBC graft covered with an ePTFE barrier may induce more bone formation with minimal inflammation in an extraction socket compared to a collagen plug with calcium apatite crystals. In addition, histological analysis of the CPCAC graft showed evidence of foreign body reaction, which indicates a negative clinical impact.

Inflammatory tissue response in human soft tissue is caused by a higher particle load near carbon fiber-reinforced PEEK compared to titanium plates.

Titanium as the leading implant material in locked plating is challenged by polymers such as carbon fiber-reinforced polyetheretherketone (CFR-PEEK), which became the focus of interest of researchers and manufacturers in recent years. However, data on human tissue response to these new implant materials are rare. Osteosynthesis plates and peri­implant soft tissue samples of 16 healed proximal humerus fractures were examined (n = 8 CFR-PEEK, n = 8 titanium). Soft tissue was analyzed by immunohistochemistry and µCT. The entrapped foreign bodies were further examined for their material composition by FTIR. To gain insight into their origin and formation mechanism, explanted and new plates were evaluated by SEM, EDX, profilometry and HR-CT. In the peri­implant soft tissue of the CFR-PEEK plates, an inflammatory tissue reaction was detected. Tissues contained foreign bodies, which could be identified as tantalum wires, carbon fiber fragments and PEEK particles. Titanium particles were also found in the peri­implant soft tissue of the titanium plates but showed a less intense surrounding tissue inflammation in immunohistochemistry. The surface of explanted CFR-PEEK plates was rougher and showed exposed and broken carbon fibers as well as protruding and deformed tantalum wires, especially in used screw holes, whereas scratches were identified on the titanium plate surfaces. Particles were present in the peri­implant soft tissue neighboring both implant materials and could be clearly assigned to the plate material. Particles from both plate materials caused detectable tissue inflammation, with more inflammatory cells found in soft tissue over CFR-PEEK plates than over titanium plates. STATEMENT OF SIGNIFICANCE: Osteosynthesis plates are ubiquitously used in various medical specialties for the reconstruction of bone fractures and defects and are therefore indispensable for trauma surgeons, ENT specialists and many others. The leading implant material are metals such as titanium, but recently implants made of polymers such as carbon fiber-reinforced polyetheretherketone (CFR-PEEK) have become increasingly popular. However, little is known about human tissue reaction and particle generation related to these new implant types. To clarify this question, 16 osteosynthesis plates (n = 8 titanium and n = 8 CFR-PEEK) and the overlying soft tissue were analyzed regarding particle occurrence and tissue inflammation. Tissue inflammation is clinically relevant for the development of scar tissue, which is discussed to cause movement restrictions and thus contributes significantly to patient outcome.

Diamond-Like Carbon Depositing on the Surface of Polylactide Membrane for Prevention of Adhesion Formation During Tendon Repair.

Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine. This study proposes the use of diamond-like carbon (DLC) deposited on polylactic acid (PLA) membranes as a biophysical mechanism for anti-adhesion barrier to encase ruptured tendons in tendon-injured rats. The results indicate that PLA/DLC composite membrane exhibits more efficient anti-adhesion effect than PLA membrane, with histological score decreasing from 3.12 ± 0.27 to 2.20 ± 0.22 and anti-adhesion effectiveness increasing from 21.61% to 44.72%. Mechanistically, the abundant C=O bond functional groups on the surface of DLC can reduce reactive oxygen species level effectively; thus, the phosphorylation of NF-κB and M1 polarization of macrophages are inhibited. Consequently, excessive inflammatory response augmented by M1 macrophage-originated cytokines including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) is largely reduced. For biocompatibility evaluation, PLA/DLC membrane is slowly absorbed within tissue and displays prolonged barrier effects compared to traditional PLA membranes. Further studies show the DLC depositing decelerates the release of degradation product lactic acid and its induction of macrophage M2 polarization by interfering esterase and PLA ester bonds, which further delays the fibrosis process. It was found that the PLA/DLC membrane possess an efficient biophysical mechanism for treatment of peritendinous adhesion.

The Potential for Foreign Body Reaction of Implanted Poly-L-Lactic Acid: A Systematic Review.

Poly-L-lactic acid (PLLA) implants have been used for bone fixation for decades. However, upon insertion, they can cause a foreign body reaction (FBR) that may lead to complications. On 15 December 2023, a systematic review was conducted to search for articles on the PubMed, MeSH term, and Scopus databases using the keywords 'PLLA' and 'foreign body reaction'. The articles were reviewed not only for the question of FBR, its severity, and the manifestation of symptoms but also for the type of implant and its location in the body, the species, and the number of individuals included. A total of 71 original articles were identified. Of these, two-thirds reported on in vivo trials, and one-third reported on clinical applications. The overall majority of the reactions were mild in more than half of the investigations. Symptoms of extreme and extensive FBR mainly include osteolysis, ganglion cysts, and swelling. The localization of PLLA implants in bone can often result in osteolysis due to local acidosis. This issue can be mitigated by adding hydroxyapatite. There should be no strong FBR when PLLA is fragmented to 0.5-4 µm by extracorporeal shock wave.

Medical textile implants: hybrid fibrous constructions towards improved performances.

OBJECTIVES: One main challenge for textile implants is to limit the foreign body reaction (FBR) and in particular the fibrosis development once the device is implanted. Fibrotic tissue in-growth depends on the fiber size, the pore size, and the organization of the fibrous construction. Basically, non-woven fibrous assemblies present a more favorable interface to biological tissues than do woven structures. However, they are mechanically less strong. In order to combine both strength and appropriate topography properties, the design of a hybrid fibrous construct was considered and discussed in this work. METHODS: Two polyethylene terephthalate (PET) weaves (satin and plain) were assembled with a non-woven PET mat, using an ultrasound welding process. RESULTS: The physical and mechanical properties of the construction as well as its ability to interact with the biological environment were then evaluated. In particular, the wettability of the obtained substrate as well as its ability to interact with mesenchymal stem cells (MSC) at 24 h (adhesion) and 72 h (proliferation) in vitro were studied. CONCLUSIONS: The results show that the non-woven layer helps limiting cell proliferation in the plain weave construction and promotes conversely proliferation in the satin construction.

Complicaciones perianales causadas por agentes modeladores inyectados en glúteos / Perianal complications caused by gluteal injection of modeling agents

En este reporte presentamos tres pacientes en quienes ocurrieron condiciones inflamatorias perianales tardías, luego de la administración de sustancias modeladoras no identificadas en los glúteos. El diagnóstico inicial y supuesto no fue correcto, ya que no se investigó durante la evaluación preliminar el antecedente de la administración de elementos modeladores. Recomendamos que los pacientes con patologías inflamatorias del ano, sobre todo aquellos cuyo curso es extraño, se les pregunte acerca de la administración de agentes modeladores en los glúteos. Esta práctica puede contribuir a la eficacia del diagnóstico de manifestaciones perianales caracterizadas por flogosis, que se presentan de forma inusual. (AU)

In this report we present three patients in which late perianal inflammatory conditions occurred after administration of unidentified modeling agents to the buttocks. The initial diagnosis was not correct because of the administration of modeling agents was not investigated during the initial eval-uation. We recommend inquiring patients with inflammatory pathologies of the anus, especially those whose course is unusual, about the adminis-tration of modeling agents to the buttocks. This approach can contribute to the efficiency of the diagnosis of perianal complaints characterized by inflammation, but rare in its appearance. (AU)

M2 macrophage-derived exosome-functionalized topological scaffolds regulate the foreign body response and the coupling of angio/osteoclasto/osteogenesis.

Designing scaffolds that can regulate the innate immune response and promote vascularized bone regeneration holds promise for bone tissue engineering. Herein, electrospun scaffolds that combined physical and biological cues were fabricated by anchoring reparative M2 macrophage-derived exosomes onto topological pore structured nanofibrous scaffolds. The topological pore structure of the fiber and the immobilization of exosomes increased the nanoscale roughness and hydrophilicity of the fibrous scaffold. In vitro cell experiments showed that exosomes could be internalized by target cells to promote cell migration, tube formation, osteogenic differentiation, and anti-inflammatory macrophage polarization. The activation of fibrosis, angiogenesis, and macrophage was elucidated during the exosome-functionalized fibrous scaffold-mediated foreign body response (FBR) in subcutaneous implantation in mice. The exosome-functionalized nanofibrous scaffolds also enhanced vascularized bone formation in a critical-sized rat cranial bone defect model. Importantly, histological analysis revealed that the biofunctional scaffolds regulated the coupling effect of angiogenesis, osteoclastogenesis, and osteogenesis by stimulating type H vessel formation. This study elaborated on the complex processes within the cell microenvironment niche during fibrous scaffold-mediated FBR and vascularized bone regeneration to guide the design of implants or devices used in orthopedics and maxillofacial surgery. STATEMENT OF SIGNIFICANCE: How to design scaffold materials that can regulate the local immune niche and truly achieve functional vascularized bone regeneration still remain an open question. Here, combining physical and biological cues, we proposed new insight to cell-free and growth factor-free therapy, anchoring reparative M2 macrophage-derived exosomes onto topological pore structured nanofibrous scaffolds. The exosomes functionalized-scaffold system mitigated foreign body response, including excessive fibrosis, tumor-like vascularization, and macrophage activation. Importantly, the biofunctional scaffolds regulated the coupling effect of angiogenesis, osteoclastogenesis, and osteogenesis by stimulating type H vessel formation.

[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.

Resveratrol Alleviates the Early Challenges of Implant-Based Drug Delivery in a Human Glial Cell Model.

Brain diseases are oftentimes life-threatening and difficult to treat. The local administration of drug substances using brain implants can increase on-site concentrations and decrease systemic side effects. However, the biocompatibility of potential brain implant materials needs to be evaluated carefully as implants can trigger foreign body reactions, particularly by increasing the microglia and astrocyte reactivity. To date, these tests have been frequently conducted in very simple in vitro models, in particular not respecting the key players in glial cell reactions and the challenges of surgical implantation characterized by the disruption of oxygen and nutrient supply. Thus, we established an in vitro model in which we treated human glial cell lines with reduced oxygen and glucose levels. The model displayed cytokine and reactive oxygen species release from reactive microglia and an increase in a marker of reactive astrocytes, galectin-3. Moreover, the treatment caused changes in the cell survival and triggered the production of hypoxia-inducible factor 1α. In this comprehensive platform, we demonstrated the protective effect of the natural polyphenol resveratrol as a model substance, which might be included in brain implants to ease the undesired glial cell response. Overall, a glial-cell-based in vitro model of the initial challenges of local brain disease treatment may prove useful for investigating new therapy options.

Inflammasomes as regulators of mechano-immunity.

Mechano-immunity, the intersection between cellular or tissue mechanics and immune cell function, is emerging as an important factor in many inflammatory diseases. Mechano-sensing defines how cells detect mechanical changes in their environment. Mechano-response defines how cells adapt to such changes, e.g. form synapses, signal or migrate. Inflammasomes are intracellular immune sensors that detect changes in tissue and cell homoeostasis during infection or injury. We and others recently found that mechano-sensing of tissue topology (swollen tissue), topography (presence and distribution of foreign solid implant) or biomechanics (stiffness), alters inflammasome activity. Once activated, inflammasomes induce the secretion of inflammatory cytokines, but also change cellular mechanical properties, which influence how cells move, change their shape, and interact with other cells. When overactive, inflammasomes lead to chronic inflammation. This clearly places inflammasomes as important players in mechano-immunity. Here, we discuss a model whereby inflammasomes integrate pathogen- and tissue-injury signals, with changes in tissue mechanics, to shape the downstream inflammatory responses and allow cell and tissue mechano-adaptation. We will review the emerging evidence that supports this model.

Zwitterion mediated anti-protein adsorption on polypropylene mesh to reduce inflammation for efficient hernia repair.

The effectiveness of polypropylene (PP) mesh is often compromised by severe inflammation. Engineering anti-inflammatory coatings has significant implications for PP mesh to repair unwanted hernias. Here, we presented a facile strategy to develop an anti-fouling coating consisting of zwitterionic poly(carboxybetaine methacrylate) (PCBMA), which could prohibit protein adsorption to endow PP mesh with anti-inflammatory efficacy. The incorporation of PCBMA coating had little impact on the raw features of PP mesh. While the modified mesh PCBMA-PP possessed noticeable hydrophilicity increase and surface charge reduction. The excellent lubricity and surface stability enabled PCBMA-PP to exhibit superior anti-fouling capacity, thus efficiently inhibiting the adsorption of proteins. In vivo experiments showed that incorporating the PCBMA layer could provide PP meshes with outstanding anti-inflammatory effects and tissue compatibility for repairing hernias.

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.

Releasable, Immune-Instructive, Bioinspired Multilayer Coating Resists Implant-Induced Fibrosis while Accelerating Tissue Repair.

Implantable biomaterials trigger foreign body reactions (FBRs), which reduces the functional life of medical devices and prevents effective tissue regeneration. Although existing therapeutic approaches can circumvent collagen-rich fibrotic encapsulation secondary to FBRs, they disrupt native tissue repair. Herein, a new surface engineering strategy in which an apoptotic-mimetic, immunomodulatory, phosphatidylserine liposome (PSL) is released from an implant coating to induce the formation of a macrophage phenotype that mitigates FBRs and improves tissue healing is described. PSL-multilayers constructed on implant surfaces via the layer-by-layer method release PSLs over a 1-month period. In rat muscles, poly(etheretherketone) (PEEK), a nondegradable polymer implant model, induces FBRs with dense fibrotic scarring under an aberrant cellular profile that recruits high levels of inflammatory infiltrates, foreign body giant cells (FBGCs), scar-forming myofibroblasts, and inflammatory M1-like macrophages but negligible amounts of anti-inflammatory M2-like phenotypes. However, the PSL-multilayer coating markedly diminishes these detrimental signatures by shifting the macrophage phenotype. Unlike other therapeutics, PSL-multilayered coatings also stimulate muscle regeneration. This study demonstrates that PSL-multilayered coatings are effective in eliminating FBRs and promoting regeneration, hence offering potent and broad applications for implantable biomaterials.

Calming the Nerves via the Immune Instructive Physiochemical Properties of Self-Assembling Peptide Hydrogels.

Current therapies for the devastating damage caused by traumatic brain injuries (TBI) are limited. This is in part due to poor drug efficacy to modulate neuroinflammation, angiogenesis and/or promoting neuroprotection and is the combined result of challenges in getting drugs across the blood brain barrier, in a targeted approach. The negative impact of the injured extracellular matrix (ECM) has been identified as a factor in restricting post-injury plasticity of residual neurons and is shown to reduce the functional integration of grafted cells. Therefore, new strategies are needed to manipulate the extracellular environment at the subacute phase to enhance brain regeneration. In this review, potential strategies are to be discussed for the treatment of TBI by using self-assembling peptide (SAP) hydrogels, fabricated via the rational design of supramolecular peptide scaffolds, as an artificial ECM which under the appropriate conditions yields a supramolecular hydrogel. Sequence selection of the peptides allows the tuning of these hydrogels' physical and biochemical properties such as charge, hydrophobicity, cell adhesiveness, stiffness, factor presentation, degradation profile and responsiveness to (external) stimuli. This review aims to facilitate the development of more intelligent biomaterials in the future to satisfy the parameters, requirements, and opportunities for the effective treatment of TBI.

Foreign Body Reaction Requiring Re-Exploration After Tympanoplasty With Porcine Small Intestinal Submucosa Reconstruction.

OBJECTIVE: We present the first published case of large foreign body reaction to Biodesign (Cook Medical, Bloomington, IN), an acellular otologic graft matrix derived from porcine small intestinal submucosa, after use in tympanoplasty surgery in a patient without previous exposure to meat products. METHODS: A single case report of a 39-year-old female who developed tinnitus, ear drainage, and large fibrotic mass in external auditory canal and extending into middle ear after Type I medial graft tympanoplasty with Biodesign Graft. Left endoscopic microdissection and resection of the tympanic membrane and middle ear fibrotic mass were performed. MAIN FINDINGS: Surgical excision of the fibrous mass required extensive microdissection to ensure preservation of the ossicles and chorda tympani. Postoperatively, hearing improved and otalgia and otorrhea resolved. CONCLUSIONS: We report the first case of post-tympanoplasty reaction with the use of Biodesign acellular porcine graft in a patient with no previous known exposure to meat products. Although this presentation appears to be rare, it reinforces the need for careful patient selection and counseling around the use of porcine or other foreign grafts.