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. 2018 May;24(9-10):695-702.
doi: 10.1089/ten.tea.2017.0299. Epub 2018 Jan 5.

Functional Mechanics of a Pectin-Based Pleural Sealant After Lung Injury

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Free PMC article

Functional Mechanics of a Pectin-Based Pleural Sealant After Lung Injury

Andrew B Servais et al. Tissue Eng Part A. .
Free PMC article

Abstract

Pleural injury and associated air leaks are a major influence on patient morbidity and healthcare costs after lung surgery. Pectin, a plant-derived heteropolysaccharide, has recently demonstrated potential as an adhesive binding to the glycocalyx of visceral mesothelium. Since bioadhesion is a process likely involving the interpenetration of the pectin-based polymer with the glycocalyx, we predicted that the pectin-based polymer may also be an effective sealant for pleural injury. To explore the potential role of an equal (weight%) mixture of high-methoxyl pectin and carboxymethylcellulose as a pleural sealant, we compared the yield strength of the pectin-based polymer to commonly available surgical products. The pectin-based polymer demonstrated significantly greater adhesion to the lung pleura than the comparison products (p < 0.001). In a 25 g needle-induced lung injury model, pleural injury resulted in an air leak and a loss of airway pressures. After application of the pectin-based polymer, there was a restoration of airway pressure and no measurable air leak. Despite the application of large sheets (50 mm2) of the pectin-based polymer, multifrequency lung impedance studies demonstrated no significant increase in tissue damping (G) or hysteresivity (η)(p > 0.05). In 7-day survival experiments, the application of the pectin-based polymer after pleural injury was associated with no observable toxicity, 100% survival (N = 5), and restored lung function. We conclude that this pectin-based polymer is a strong and nontoxic bioadhesive with the potential for clinical application in the treatment of pleural injuries.

Keywords: adhesion; mesothelium; pectin; pleura; pneumothorax.

Conflict of interest statement

No competing financial interests exist.

Figures

<b>FIG. 1.</b>
FIG. 1.
Preparation and application of the pectin-based polymer. Based on previous work, a 50–50 (wt%) mixture of HMP and CMC was used. (A) The HMP and CMC mixture was prepared as a viscous liquid, poured into the desired mold, and allowed to dry overnight into a translucent 50 μm thick sheet (48.3 ± 13 μm). (B) The pectin-based polymer was applied to the lung surface with 1–2 min of gentle pressure. Subsequent SEM demonstrated intimate integration of the polymer with the existing pleura. Arrows highlight the edge of the pectin polymer covering the mesothelial microvilli. CMC, carboxymethylcellulose; HMP, high methoxyl pectin; SEM, scanning electron microscopy. Color images available online at www.liebertpub.com/tea
<b>FIG. 2.</b>
FIG. 2.
Load/displacement measurements. The adhesion of lung pleura to different surgical products was measured by a load/displacement assay (inset). Ninety degree loads were applied at a controlled rate to a suture passed through the tissue near the adhesive interface. Displacement was a measure of the separation at the adherend-substratum interface. (A) Representative load/displacement curves for the pectin-based polymer and five commercially available surgical products are shown. The curves were highly reproducible at displacement distances less than 3 mm; greater variability was noted between 3 and 6 mm (representative estimates shown). (B) Replicates of the initial separation load (yield point) demonstrated significantly greater adhesion of the pectin-based polymer than the surgical products (p < 0.001; N = 5). Color images available online at www.liebertpub.com/tea
<b>FIG. 3.</b>
FIG. 3.
Model of pleural injury. (A) A pleural injury in the left lung was produced with a 25 g needle inserted 1–2 mm into the lung parenchyma. Blood and a bubbling air leak were immediately noted. (B) Scanning electron microscopy of a double puncture of the lung demonstrated the associated pleural injury. Note the absence of a subpleural extracellular matrix to support wound healing. Color images available online at www.liebertpub.com/tea
<b>FIG. 4.</b>
FIG. 4.
Representative respiratory system mechanics after pleural injury. After standardizing volume history, a recruitment maneuver was performed consisting of a 3-s ramp to a 30 cm H2O airway pressure followed by a 3-s plateau. (A) After a single 25 g needle-induced pleural injury, the recruitment maneuver demonstrated a plateau pressure of ∼15 cm H2O. After sealing the injury with the pectin-based polymer, the repeat recruitment maneuver restored the 30 cm H2O airway pressures. (B) After a through-and-through injury of the lung, the pressures similarly dropped to less than half of the 30 cm H2O plateau pressures (Injury × 2). Sealing one of the injuries with the pectin-based polymer increased plateau pressures (Seal × 1). Also sealing the second injury (Seal × 2) resulted in restoration of baseline airway pressures. Note the two phases of the pressure curve: the initial exponential decline in airway pressures followed by a quasi-plateau phase. Summary data of a single pleural injury are shown in Figure 7. Color images available online at www.liebertpub.com/tea
<b>FIG. 5.</b>
FIG. 5.
Effect of sealants on peripheral lung mechanics. Lung impedance measurements were made using a forced oscillation technique (FlexiVent). The no sealant condition (Baseline) was compared to two sizes of the pectin-based polymer (1xPectin, 25 mm2; 2xPectin, 50 mm2) as well as two volumes of a cyanoacrylate (CA, VetBond) sealant (1gtt, 25 μL; 2gtt, 50 μL). (A) Measurement of tissue damping (G) demonstrated a slight increase in the 2xPectin condition (p > 0.05), but a significant increase in both cyanoacrylate conditions (asterisk, p < 0.01). (B) Hysteresivity, reflecting the relationship between energy dissipation and energy conservation (elastance), demonstrated no difference in the pectin-based polymer conditions, but a significant increase in the cyanoacrylate treatment groups (asterisk, p < 0.01). Triplicate measures per mouse; each data point represents N = 3 mice.
<b>FIG. 6.</b>
FIG. 6.
Appearance of pectin-based polymer 7 days after application onto a pleural injury. (A) A left lung injury (25 g needle) was acutely sealed with the pectin-based polymer and the thoracotomy closed. After 7 days, the mice were euthanized. The lungs were flushed to facilitate identification of the polymer (circle). (B) SEM of the pleura demonstrated a similar appearance to the acute application with some discontinuous or “patchy” areas near the edges (arrows) of the applied pectin. Color images available online at www.liebertpub.com/tea
<b>FIG. 7.</b>
FIG. 7.
Respiratory system mechanics 7 days after application of the pectin-based polymer. (A) Acutely after injury with a 25 g needle, significantly decreased plateau pressures (asterisk, p < 0.001) were restored after application of the pectin-based polymer. The plateau pressures remained at baseline levels after 7 days. (B) Similarly, the significant increase in ventilated volume (“leak volume”) after pleural injury (asterisk, p < 0.001) was normalized after application of the pectin-based sealant. The ventilatory efficiency remained unchanged after 7 days. Triplicate measures per mouse; each data point represents, N = 5 mice.

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