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Immunocompatible elastomer with increased resistance to the foreign body response.

ABSTRACT: 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.

SUBMITTER: Zhou X

PROVIDER: S-EPMC11364871 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Immunocompatible elastomer with increased resistance to the foreign body response.

Zhou Xianchi X Lu Zhouyu Z Cao Wenzhong W Zhu Zihao Z Chen Yifeng Y Ni Yanwen Y Liu Zuolong Z Jia Fan F Ye Yang Y Han Haijie H Yao Ke K Liu Weifeng W Wang Youxiang Y Ji Jian J Zhang Peng P

Nature communications 20240830 1

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 ...[more]

PMID: 39214984

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Project description:Implantable glucose biosensors provide real-time information about blood glucose fluctuations, but their utility and accuracy are time-limited due to the foreign body response (FBR) following their insertion beneath the skin. The slow release of nitric oxide (NO), a gasotransmitter with inflammation regulatory properties, from a sensor surface has been shown to dramatically improve sensors' analytical biocompatibility by reducing the overall FBR response. Indeed, work in a porcine model suggests that as long as the implants (sensors) continue to release NO, even at low levels, the inflammatory cell infiltration and resulting collagen density are lessened. While these studies strongly support the benefits of NO release in mitigating the FBR, the mechanisms through which exogenous NO acts on the surrounding tissue, especially under the condition of hyperglycemia, remain vague. Such knowledge would inform strategies to refine appropriate NO dosage and release kinetics for optimal therapeutic activity. In this study, we evaluated mediator, immune cell, and mRNA expression profiles in the local tissue microenvironment surrounding implanted sensors as a function of NO release, diabetes, and implantation duration. A custom porcine wound healing-centric multiplex gene array was developed for nanoString barcoding analysis. Tissues adjacent to sensors with sustained NO release abrogated the implant-induced acute and chronic FBR through modulation of the tissue-specific immune chemokine and cytokine microenvironment, resulting in decreased cellular recruitment, proliferation, and activation at both the acute (7-d) and chronic (14-d) phases of the FBR. Further, we found that sustained NO release abrogated the implant-induced acute and chronic foreign body response through modulation of mRNA encoding for key immunological signaling molecules and pathways, including STAT1 and multiple STAT1 targets including MAPK14, IRAK4, MMP2, and CXCL10. The condition of diabetes promoted a more robust FBR to the implants, which was also controlled by sustained NO release.

Project description:The clinical manifestations of foreign body (FB) aspiration can range from an asymptomatic presentation to a life-threatening emergency. Patients may present with acute onset cough, chest pain, breathlessness or sub-acutely with unexplained hemoptysis, non-resolving pneumonia and at times, as an incidental finding on imaging. Patients with iatrogenic FB such as an aspirated broken tooth during difficult intubation or a broken instrument are more common scenarios in the intensive care unit (ICU). Patients with post-obstructive pneumonia with or without sepsis, or variable degree of hemoptysis often require ICU level of care and bronchoscopic interventions. Rigid bronchoscopy has traditionally been the modality of choice; however, with the innovation in instrumentation and wider availability of flexible bronchoscopes, most of the FB removal is now successfully performed using flexible bronchoscopy. Proceduralists choose instruments in accordance with their training and expertise. We describe the use of most common instruments including forceps, balloon catheters, and baskets. Role of cryoprobe and LASER in FB removal is reviewed as well. In general, larger working channel bronchoscopes are preferred; however, smaller working channel bronchoscopes may be used in situations when the patients are intubated with a smaller diameter endotracheal or tracheostomy tubes. Large size FB are removed en bloc with the grasping tool, bronchoscope, and endotracheal or tracheostomy tube, requiring preparation to safely re-establish the airway. After FB removal, bronchoscopy is re-performed to identify any residual FB, assess any injury to the airway, suction post-obstructive secretions or pus, control any active bleeding and remove granulation tissue that may be obstructing the airway. Additional interventions like balloon dilatation may be required to dislodge an impacted FB or to maintain patency of bronchial lumen. If bronchoscopic methods fail, surgery may be required for retrieval of FB in symptomatic patients or to resect suppurative or necrotizing lung process. Multidisciplinary approach involving intensivists, surgeons, and anesthesiologists is the key to optimal patient outcomes.

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Immunocompatible elastomer with increased resistance to the foreign body response.

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Immunocompatible elastomer with increased resistance to the foreign body response.

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