Foreign Body Response and Intravital Microscopy on AIW in Mice

Shannen K. Sharpe; Michelle M. Martinez; Kenneth W. Dunn

doi:10.18060/25705

Foreign Body Response and Intravital Microscopy on AIW in Mice

Proceedings of IMPRS ◽

10.18060/25705 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Shannen K. Sharpe ◽

Michelle M. Martinez ◽

Kenneth W. Dunn

Keyword(s):

Foreign Body ◽

Medical Devices ◽

Immune Cells ◽

Intravital Microscopy ◽

Cell Biology ◽

Foreign Body Response ◽

Coating Materials ◽

Local Inflammatory Response ◽

Window System ◽

Body Response

The foreign body response is the body’s response to the insertion of an object. The foreign body response consists of two components, the innate and adaptive immune response, and lasts for the life of the inserted object. Accordingly, the foreign body response represents a significant challenge to the development of implanted medical devices. In addition to triggering the damaging consequences of inflammation, the foreign body response acts to encapsulate and isolate inserted objects, limiting the functional lifetime of medical devices such as glucose monitors. Accordingly, significant efforts have been devoted to understanding the cell biology of the foreign body response to identify approaches for limiting surface “biofouling”. We have developed an indwelling window system that support longitudinal intravital microscopy of mice. In studies of transgenic mice expressing fluorescent immune cells, we found that the window triggers a local inflammatory response. To explore the utility of this window system as an experimental platform for characterizing the foreign body response, we conducted an intravital microscopy study of 8 mice expressing GFP in myeloid immune cells (Lys-EGFP mice) with surgically implanted abdominal imaging windows. To identify differences in the responses to different surface chemistries, the windows were either left uncoated or coated with poly-L-lysine or type V mouse collagen prior to insertion. Intravital multiphoton microscopy studies conducted over a period of up to 3 weeks demonstrated that the window instigated a local recruitment of immune cells, followed by vascularization and giant cell formation that varied depending upon window surface treatment. These studies demonstrate the utility of the abdominal window as a model system for studying the cell biology of the foreign body response and represent the template for subsequent studies designed to compare the foreign body response to different coating materials designed to extend the useful lifetime of implanted devices.

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Allometric tissue-scale forces activate mechanoresponsive immune cells to drive pathological foreign body response to biomedical implants

10.1101/2022.01.14.476395 ◽

2022 ◽

Author(s):

Jagannath Padmanabhan ◽

Kellen Chen ◽

Dharshan Sivaraj ◽

Britta A Kuehlmann ◽

Clark A Bonham ◽

...

Keyword(s):

Mechanical Properties ◽

Foreign Body ◽

Immune Cells ◽

Immune Cell ◽

Implantable Devices ◽

Foreign Body Response ◽

Biomedical Implants ◽

Independent Variable ◽

First Time ◽

Body Response

For decades, it has been assumed that the foreign body response (FBR) to biomedical implants is primarily a reaction to the chemical and mechanical properties of the implant. Here, we show for the first time that a third independent variable, allometric tissue-scale forces (which increase exponentially with body size), can drive the biology of FBR in humans. We first demonstrate that pathological FBR in humans is mediated by immune cell-specific Rac2 mechanotransduction signaling, independent of implant chemistry or mechanical properties. We then show that mice, which are typically poor models of human FBR, can be made to induce a strikingly human-like pathological FBR by altering these extrinsic tissue forces. Altering these extrinsic tissue forces alone activates Rac2 signaling in a unique subpopulation of immune cells and results in a human-like pathological FBR at the molecular, cellular, and local tissue levels. Finally, we demonstrate that blocking Rac2 signaling negates the effect of increased tissue forces, dramatically reducing FBR. These findings highlight a previously unsuspected mechanism for pathological FBR and may have profound implications for the design and safety of all implantable devices in humans.

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Examination of the foreign body response to biomaterials by nonlinear intravital microscopy

Nature Biomedical Engineering ◽

10.1038/s41551-016-0007 ◽

2016 ◽

Vol 1 (1) ◽

Cited By ~ 63

Author(s):

Eleonora Dondossola ◽

Boris M. Holzapfel ◽

Stephanie Alexander ◽

Stefano Filippini ◽

Dietmar W. Hutmacher ◽

...

Keyword(s):

Foreign Body ◽

Intravital Microscopy ◽

Foreign Body Response ◽

Body Response

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Examinations of a new long-term degradable electrospun polycaprolactone scaffold in three rat abdominal wall models

Journal of Biomaterials Applications ◽

10.1177/0885328216687664 ◽

2017 ◽

Vol 31 (7) ◽

pp. 1077-1086 ◽

Cited By ~ 3

Author(s):

Hanna Jangö ◽

Søren Gräs ◽

Lise Christensen ◽

Gunnar Lose

Keyword(s):

Pelvic Organ Prolapse ◽

Foreign Body ◽

Abdominal Wall ◽

Muscle Fiber ◽

Pelvic Organ ◽

Foreign Body Response ◽

Heavy Load ◽

Tissue Construct ◽

Body Response

Alternative approaches to reinforce native tissue in reconstructive surgery for pelvic organ prolapse are warranted. Tissue engineering combines the use of a scaffold with the regenerative potential of stem cells and is a promising new concept in urogynecology. Our objective was to evaluate whether a newly developed long-term degradable polycaprolactone scaffold could provide biomechanical reinforcement and function as a scaffold for autologous muscle fiber fragments. We performed a study with three different rat abdominal wall models where the scaffold with or without muscle fiber fragments was placed (1) subcutaneously (minimal load), (2) in a partial defect (partial load), and (3) in a full-thickness defect (heavy load). After 8 weeks, no animals had developed hernia, and the scaffold provided biomechanical reinforcement, even in the models where it was subjected to heavy load. The scaffold was not yet degraded but showed increased thickness in all groups. Histologically, we found a massive foreign body response with numerous large giant cells intermingled with the fibers of the scaffold. Cells from added muscle fiber fragments could not be traced by PKH26 fluorescence or desmin staining. Taken together, the long-term degradable polycaprolactone scaffold provided biomechanical reinforcement by inducing a marked foreign-body response and attracting numerous inflammatory cells to form a strong neo-tissue construct. However, cells from the muscle fiber fragments did not survive in this milieu. Properties of the new neo-tissue construct must be evaluated at the time of full degradation of the scaffold before its possible clinical value in pelvic organ prolapse surgery can be evaluated.

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Beneficial effects of hydrocortisone or spironolactone coating on foreign body response to mesh biomaterial in a mouse model

Journal of Biomedical Materials Research Part A ◽

10.1002/jbm.a.33136 ◽

2011 ◽

Vol 99A (3) ◽

pp. 335-343 ◽

Cited By ~ 16

Author(s):

Christopher J. Brandt ◽

Daniel Kammer ◽

Anette Fiebeler ◽

Uwe Klinge

Keyword(s):

Foreign Body ◽

Mouse Model ◽

Foreign Body Response ◽

Beneficial Effects ◽

Body Response

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Mitigating the foreign body response through ‘immune-instructive’ biomaterials

Journal of Immunology and Regenerative Medicine ◽

10.1016/j.regen.2021.100040 ◽

2021 ◽

Vol 12 ◽

pp. 100040

Author(s):

Lisa Kämmerling ◽

Leanne E. Fisher ◽

Ezgi Antmen ◽

Gorkem M. Simsek ◽

Hassan M. Rostam ◽

...

Keyword(s):

Foreign Body ◽

Foreign Body Response ◽

Body Response

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A Polymer-Biologic Hybrid Hernia Construct: Review of Data and Early Experiences

Polymers ◽

10.3390/polym13121928 ◽

2021 ◽

Vol 13 (12) ◽

pp. 1928

Author(s):

Michael Sawyer ◽

Stephen Ferzoco ◽

George DeNoto

Keyword(s):

Foreign Body ◽

Hernia Repair ◽

Surgical Mesh ◽

Foreign Body Response ◽

Host Cells ◽

Mesh Reinforcement ◽

Decellularized Extracellular Matrix ◽

Early Experiences ◽

Tissue Matrix ◽

Body Response

Surgical mesh reinforcement of the human abdominal wall has been found to reduce the chance of recurrence in hernia repairs. While traditionally polymer meshes have been used in hernia repair, alternative mesh options have been engineered to prevent the inflammatory foreign body response invoked by polymers. A reinforced tissue matrix (RTM) mesh has been developed by embedding a polymer within a decellularized extracellular matrix. This combination has been attributed to the recruitment of host cells, a pro-healing response, and attenuation of the foreign body response. This has been observed to lead to the regeneration of functional tissue within the repair site that is reinforced by the polymer to offload abdominal pressures over time. This manuscript presents the review of OviTex, an RTM, in several types of hernia repair. The authors have found that the use of RTM in hernia repair is effective in preventing foreign body response, promoting wound healing, and providing reinforcement to lower the risk of hernia recurrence.

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Immunobiology and Application of Aloe vera-Based Scaffolds in Tissue Engineering

International Journal of Molecular Sciences ◽

10.3390/ijms22041708 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1708

Author(s):

Saeedeh Darzi ◽

Kallyanashis Paul ◽

Shanilka Leitan ◽

Jerome A. Werkmeister ◽

Shayanti Mukherjee

Keyword(s):

Tissue Engineering ◽

Foreign Body ◽

Scientific Evidence ◽

Aloe Vera ◽

Material Design ◽

Foreign Body Response ◽

The Body ◽

Design Strategies ◽

Immunomodulatory Effects ◽

Body Response

Aloe vera (AV), a succulent plant belonging to the Liliaceae family, has been widely used for biomedical and pharmaceutical application. Its popularity stems from several of its bioactive components that have anti-oxidant, anti-microbial, anti-inflammatory and even immunomodulatory effects. Given such unique multi-modal biological impact, AV has been considered as a biomaterial for regenerative medicine and tissue engineering applications, where tissue repair and neo-angiogenesis are vital. This review outlines the growing scientific evidence that demonstrates the advantage of AV as tissue engineering scaffolds. We particularly highlight the recent advances in the application of AV-based scaffolds. From a tissue engineering perspective, it is pivotal that the implanted scaffolds strike an appropriate foreign body response to be well-accepted in the body without complications. Herein, we highlight the key cellular processes that regulate the foreign body response to implanted scaffolds and underline the immunomodulatory effects incurred by AV on the innate and adaptive system. Given that AV has several beneficial components, we discuss the importance of delving deeper into uncovering its action mechanism and thereby improving material design strategies for better tissue engineering constructs for biomedical applications.

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