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Meningeal inflammatory response and fibrous tissue remodeling around intracortical implants: An in vivo two-photon imaging study.

ABSTRACT: Meningeal inflammation and encapsulation of neural electrode arrays is a leading cause of device failure, yet little is known about how it develops over time or what triggers it. This work characterizes the dynamic changes of meningeal inflammatory cells and collagen-I in order to understand the meningeal tissue response to neural electrode implantation. We use in vivo two-photon microscopy of CX3CR1-GFP mice over the first month after electrode implantation to quantify changes in inflammatory cell behavior as well as meningeal collagen-I remodeling. We define a migratory window during the first day after electrode implantation hallmarked by robust inflammatory cell migration along electrodes in the meninges as well as cell trafficking through meningeal venules. This migratory window attenuates by 2 days post-implant, but over the next month, the meningeal collagen-I remodels to conform to the surface of the electrode and thickens. This work shows that there are distinct time courses for initial meningeal inflammatory cell infiltration and meningeal collagen-I remodeling. This may indicate a therapeutic window early after implantation for modulation and mitigation of meningeal inflammation.

SUBMITTER: Eles JR

PROVIDER: S-EPMC6350934 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Meningeal inflammatory response and fibrous tissue remodeling around intracortical implants: An in vivo two-photon imaging study.

Eles J R JR Vazquez A L AL Kozai T D Y TDY Cui X T XT

Biomaterials 20181231

Meningeal inflammation and encapsulation of neural electrode arrays is a leading cause of device failure, yet little is known about how it develops over time or what triggers it. This work characterizes the dynamic changes of meningeal inflammatory cells and collagen-I in order to understand the meningeal tissue response to neural electrode implantation. We use in vivo two-photon microscopy of CX3CR1-GFP mice over the first month after electrode implantation to quantify changes in inflammatory c ...[more]

PMID: 30634095

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Project description:Our understanding of biomaterials in the brain have been greatly enhanced by advancements in in vivo imaging technologies such as two-photon microscopy. However, when applied to chronic studies, two-photon microscopy enables high-resolution imaging only in superficial regions due to inflammatory responses introduced by the craniotomy and insertion of foreign biomaterials. Microprisms provide a unique vertical view from brain surface to ~1 mm deep or more (depending on the size of the microprisms) which may break through this limitation on imaging depth. Although microprism has been used in the field of neuroscience, the in vivo foreign body responses to the microprism implant have yet to be fully elucidated. This is of important concern in broader applications of this approach, especially for neuroinflammation-sensitive studies. In this work, we first assessed the activation of microglia/macrophages for 16 weeks after microprism implantation using two-photon microscopy in awake CX3CR1-GFP mice. The imaging window became clear from bleedings after ~2 weeks and the maximum imaging distance (in the horizontal direction) stabilized at around 500 μm after ~5 weeks. We also quantified the microglial morphology from week 3 to week 16 post-implantation. Compared to non-implant controls, microglia near the microprism showed higher cell density, smaller soma, and shorter and less branched processes in the early-chronic phase. After week 5, microglial morphology further than 100 μm from the microprism was generally similar to microglia in the control group. In addition, time-lapse imaging confirmed that microglial processes were surveying normally from week 3, even for microglia as close as 50 μm away. These morphological analyses and dynamic imaging results suggest that microglia around chronically implanted microprism eventually exhibit inactive phenotypes. Next, we examined microglial/macrophage responses following laser induced micro-vessel disruptions as an example application of microprism implantation for neuroinflammation related studies. Through the microprism, we captured microglial/macrophage polarization and migration, as well as blood flow changes after the insult for additional 16 weeks. To our surprise, microglia/macrophage aggregation around the insult site was sustained over the 16-week observation period. This work demonstrates the feasibility of using microprisms for long-term characterizations of inflammatory responses to other injuries including implantable devices at deeper depths than that achievable by conventional two-photon microscopy.

Project description:PURPOSE:To present a case series of zygomatic implants combined with bone regeneration and soft tissue enhancement techniques to reduce the risk of biological delayed complications such as maxillary sinusitis and soft tissue recession. MATERIALS AND METHODS:Zygomatic implants placed simultaneously with different bone regeneration techniques (buccal, palatal and buccal-palatal bone regeneration) and soft tissue enhancement techniques (pediculate and free connective tissue graft) were followed for at least 12 months. The following information was collected: patient age and sex, number of zygomatic implants, zygomatic implant success rate, zygomatic implant position according to classification of the Zygomatic Anatomy Guide Approach (ZAGA), sinus membrane perforation, type and outcome of the bone regeneration or the soft tissue enhancement technique, bone gain (width and length along the zygomatic implant) and keratinized buccal mucosa width, duration of follow-up, loading protocol (immediate or delayed) and biological complications (maxillary sinusitis and soft tissue recession). RESULTS:Thirty-one zygomatic implants placed in 19 patients were included. All implants were successful and none of the implants presented biological complications. The bone regeneration technique was successful in 30 of 31 cases with a mean palatal bone width of 3 mm, buccal bone width of 2.65 mm, palatal bone length of 6.5 mm and buccal bone length of 8.3 mm. The success rate of soft tissue enhancement was 100% and it established at least 2 mm of keratinized buccal mucosa width in all implants. CONCLUSIONS:Within the limitations of the present study, bone regeneration and soft tissue enhancement techniques were useful to establish more favorable conditions of the peri-implant tissues around zygomatic implants. This could prevent biological complications such as maxillary sinusitis and soft tissue recessions. Prospective and randomized controlled clinical trials with longer follow-up periods are advisable.

Dataset Information

Meningeal inflammatory response and fibrous tissue remodeling around intracortical implants: An in vivo two-photon imaging study.

Publications

Meningeal inflammatory response and fibrous tissue remodeling around intracortical implants: An in vivo two-photon imaging study.

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