Polymeric elastomers are extensively employed to fabricate implantable medical devices. However, implantation of the elastomers can induce a strong immune rejection known as the foreign body response (FBR), diminishing their efficacy. Herein, we present a group of immunocompatible elastomers, termed easy-to-synthesize vinyl-based anti-FBR dense elastomers (EVADE). EVADE materials effectively suppress the inflammation and capsule formation in subcutaneous models of rodents and non-human primates for at least one year and two months, respectively. Implantation of EVADE materials significantly reduces the expression of inflammation-related proteins S100A8/A9 in adjacent tissues compared to polydimethylsiloxane. We also show that inhibition or knockout of S100A8/A9 leads to substantial attenuation of fibrosis in mice, suggesting a target for fibrosis inhibition. Continuous subcutaneous insulin infusion (CSII) catheters constructed from EVADE elastomers demonstrate significantly improved longevity and performance compared to commercial catheters. The EVADE materials reported here may enhance and extend function in various medical devices by resisting the local immune responses.

Polymeric elastomers are widely utilized in implantable biomedical devices. Nevertheless, the implantation of these elastomers can provoke a robust foreign body response (FBR), leading to the rejection of foreign implants and consequently reducing their effectiveness in vivo. Building effective anti-FBR coatings on those implants remains challenging. Herein, we introduce a coating-free elastomer with superior immunocompatibility. A super-hydrophilic anti-fouling zwitterionic layer can be generated in situ on the surface of the elastomer through a simple chemical trigger. This elastomer can repel the adsorption of proteins, as well as the adhesion of cells, platelets, and diverse microbes. The elastomer elicited negligible inflammatory responses after subcutaneous implantation in rodents for 2 weeks. No apparent fibrotic capsule formation was observed surrounding the elastomer after 6 months in rodents. Continuous subcutaneous insulin infusion (CSII) catheters constructed from the elastomer demonstrated prolonged longevity and performance compared to commercial catheters, indicating its great potential for enhancing and extending the performance of various implantable biomedical devices by effectively attenuating local immune responses. STATEMENT OF SIGNIFICANCE: The foreign body response remains a significant challenge for implants. Complicated coating procedures are usually needed to construct anti-fibrotic coatings on implantable elastomers. Herein, a coating-free elastomer with superior immunocompatibility was achieved using a zwitterionic monomer derivative. A pure zwitterionic layer can be generated on the elastomer surface through a simple chemical trigger. This elastomer significantly reduces protein adsorption, cell and bacterial adhesion, and platelet activation, leading to minimal fibrotic capsule formation even after six months of subcutaneous implantation in rodents. CSII catheters constructed from the PQCBE-H elastomer demonstrated prolonged longevity and performance compared to commercial catheters, highlighting the significant potential of PQCBE-H elastomers for enhancing and extending the performance of various implantable biomedical devices.

The foreign body response (FBR) is an immune-mediated reaction that can occur with most biomaterials and biomedical devices. The FBR initiates a deterioration in the performance of implantable devices, representing a longstanding challenge that consistently hampers their optimal utilization. Over the last decade, significant strides are achieved based on either hydrogel design or surface modifications to mitigate the FBR. This review delves into recent material strategies aimed at mitigating the FBR. Further, the authors look forward to future novel anti-FBR materials from the perspective of clinical translation needs. Such prospective materials hold the potential to attenuate local immune responses, thereby significantly enhancing the overall performance of implantable devices.

The foreign body response (FBR) to implanted biomaterials and biomedical devices can severely impede their functionality and even lead to failure. The discovery of effective anti-FBR materials remains a formidable challenge. Inspire by the enrichment of glutamic acid (E) and lysine (K) residues on human protein surfaces, a class of zwitterionic polypeptide (ZIP) hydrogels with alternating E and K sequences to mitigate the FBR is prepared. When subcutaneously implanted, the ZIP hydrogels caused minimal inflammation after 2 weeks and no obvious collagen capsulation after 6 months in mice. Importantly, these hydrogels effectively resisted the FBR in non-human primate models for at least 2 months. In addition, the enzymatic degradability of the gel can be controlled by adjusting the crosslinking degree or the optical isomerism of amino acid monomers. The long-term FBR resistance and controlled degradability of ZIP hydrogels open up new possibilities for a broad range of biomedical applications.

BACKGROUND: 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-1β-positive cells was lower than that in the control patch.
CONCLUSIONS: Silver-loaded SA/HA hydrogel patches decreased the foreign body reaction and venous neointimal hyperplasia in rats by the inhibition of IL-33 expression.

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.

Implantable bioelectrodes for regulating and monitoring biological behaviors have become indispensable medical devices in modern healthcare, alleviating pathological symptoms such as epilepsy and arrhythmia, and assisting in reversing conditions such as deafness and blindness. In recent years, developments in the fields of materials science and biomedical engineering have contributed to advances in research on implantable bioelectrodes. However, the foreign body reaction (FBR) is still a major constraint for the long-term application of electrodes. In this paper, four types of commonly used implantable bioelectrodes are reviewed, concentrating on their background, development, and a series of complications caused by FBR after long-term implantation. Strategies for resisting FBRs are then devised in terms of physics, chemistry, and nanotechnology. We analyze the major trends in the future development of implantable bioelectrodes and outline some promising research to optimize the long-term operational stability of electrodes. Although current implantable bioelectrodes have been able to achieve good biocompatibility, low impedance, and low mechanical mismatch and trauma, these devices still face the challenge of FBR. Resistance to FBR is still the key for the long-term effectiveness of bioelectrodes, and a better understanding of the mechanisms of FBR, as well as miniaturization, long-term passivation, and coupling with gene therapy may be the way forward for the next generation of implantable bioelectrodes.

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-1β; 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-β1 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.

Foreign body response (FBR) represents an immune-mediated cascade reaction capable of inducing the rejection of foreign implants, thereby compromising their in vivo performance. Pure zwitterionic hydrogels have demonstrated the ability to resist long-term FBR, owing to their outstanding antifouling capabilities. However, achieving such a robust anti-FBR effect necessitates stringent requirements concerning the purity of zwitterionic materials, which constrains their broader functional applications. Herein, we present a biocompatible, controllably degradable, and functionalizable zwitterion-albumin hybrid hydrogel. The zwitterionic hydrogel crosslinked with serum albumin exhibits controllable degradation and excels in preventing the adsorption of various proteins and adhesion of cells and bacteria. Moreover, the hydrogel significantly alleviates the host\'s FBR compared with PEG hydrogels and particularly outperforms PEG-based cross-linker crosslinked zwitterionic hydrogels in reducing collagen encapsulation when subcutaneously implanted into mice. The zwitterion-albumin hybrid hydrogel shows potential as a functionalizable anti-FBR material in the context of implantable materials and biomedical devices.

Development of an inflammation modulating polypropylene (PP) mesh in pelvic floor repair is an urgent clinical need. This is because PP mesh for pelvic floor repair can cause a series of complications related to foreign body reactions (FBR) in postoperative period. Therefore, we successfully prepared PP composite mesh that can scavenge reactive oxygen species (ROS) and inhibit inflammation to moderate FBR by a simple method. First, a pregel layer was formed on PP mesh by dip coating. Among them, polyurethane with polythioketal (PTK) is an excellent ROS scavenger, and dopamine methacrylamide (DMA) improves the stability of the coating and synergistically scavenges ROS. Then, a composite mesh (optimal PU50-PP) was obtained by photopolymerization. The results showed that the polyurethane gel layer was able to scavenge more than 90% of free radicals and about 75% of intracellular ROS. In vitro, PU50-PP mesh significantly scavenged ROS and resisted macrophage adhesion. After implantation in the posterior vaginal wall of rats, PU50-PP eliminated 53% of ROS, inhibited inflammation (decreased IL-6, increased IL-10), and dramatically reduced collagen deposition by about 64%, compared to PP mesh. Thus, the composite PP mesh with ROS scavenging and anti-inflammatory properties provides a promising approach for mitigating FBR.