Decreased Elastin in Fibrous Capsules of ECM-Enveloped Pacemaker Implants Aidan Mathews, Allison Meer, Atara Israel, Michael Moses, Clarence Sams, Jayda Lewis, Dr. Roche de Guzman Fred DeMatteis School of Engineering and Applied Science, Hofstra University, Hempstead, NY 11549 METHODS Samples were fixed, dehydrated, then embedded in paraffin wax within cassettes. Tissues in wax were placed in molds and cut into 5 μm sections on slides. They are stained with colored dyes: Masson’s Trichrome (MT) and elastic stain (ES), and immunostained (immunohistochemistry (IHC)) with an antibody against elastin.
Elastin proteins are crosslinked to form the very flexible elastic fibers that retract back to their original form after release of load during stretching, like rubber bands. These fibers are mainly responsible for the young skin’s elasticity. They are sometimes found in other connective tissues’ extracellular matrix (ECM), together with the usual collagen and proteoglycan complex (with hyaluronic acid) fibers, specifically in fibrous capsules. Fibrous capsules are tough and thick connective tissues mainly composed of collagen fibers and cells that secrete them, the fibroblasts. They are formed in response to non-degradable foreign bodies such as an artificial pulse generator pacemaker implant with a titanium external housing for local and systemic isolation.
The elastin distribution in fibrous capsules from FbP are even throughout the thickness. 45
Elastin Coverage Area (%)
INTRODUCTION
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CONCLUSIONS The hypothesis was conditionally accepted. According to the qualitative observations from comparing the stained images, there appears to be a significant difference in the amount of elastin in the tissue that contained the ECM. The control group (Fb-P) had thicker fibrous capsules compared to the treatment group (Fb-PECM). On going work includes quantitative analysis and evaluation of cellular and ECM structural differences between groups.
Outside the Cell
hyaluronic acid
There are reported incidents of contracture in fibrous capsules that make patients (with pacemaker implants) feel uncomfortable and one of the possible explanations is the presence of elastic fibers. To address the issue, pacemaker implants can be enveloped in a more biocompatible biomaterial pouch derived from a natural ECM. Inside the Cell
Hypothesis: Fibrous capsules formed with ECM-enveloped pacemaker is thinner with less elastin compared to those without. The more the material resembles self, the less likely to develop thick fibrous capsules for walling-off.
REFERENCES
RESULTS Samples in the group Fb-PECM showed less pronounced and thin fibrous capsules (blue signal) compared to those in Fb-P based on MT staining. Additionally, the Fb-PECM group demonstrated less elastin according to ES (black stain) and IHC (brown). Fb-PECM (ES)
Fb-PECM (MT) Fb-P (MT)
To test the study hypothesis, two groups of animals (minipigs) were assigned and implanted with: • pacemaker only (Fb-P) • pacemaker in ECM (Fb-PECM) subcutaneously (under the skin) in the left and right chest area. After 3 months, implants were retrieved, and the fibrous capsules and surrounding tissues were processed for histological analyses: dye and antibody staining.
ACKNOWLEDGMENTS Fb-P (ES)
OBJECTIVES Compare the fibrous capsule response between the two groups: Fb-P and Fb-PECM and evaluate the relative distribution of elastin in tissue samples.
1. Pothineni, N. K., Kumareswaran, R., & Schaller, R. D. Pacemaker Pocket Stabilization Utilizing a Novel Envelope and Three-Point Anchoring Technique. Aziyo Biologics, 2021 Feb 3;13(2):e13108. 2. https://physiotherapymilan.it/wpcontent/uploads/2015/02/elastic-fibre.png 3. https://s3-us-west-2.amazonaws.com/coursesimages/wpcontent/uploads/sites/1223/2017/01/31001814/Figure_ 33_02_06-e1485822088926.jpg 4. https://i.pinimg.com/736x/7a/f5/75/7af5753c27f3ffcba a608ee4be5b2928--skin-elasticity-back-to.jpg
Fb-P (IHC)
Porcine tissue samples were supplied Aziyo Biologics. We also like to thank the Engineering Department for the facility access and use. All experiments were conducted in 208 Weed Hall, Department of Engineering.