TAPE: A Biodegradable Hemostatic Glue Inspired by a Ubiquitous Compound in Plants for Surgical Application (2025)

Summary

We describe the simplest protocol to prepare biodegradable medical glue that has an effective hemostatic ability. TAPE is a water-immiscible supramolecular aggregate prepared by mixing of tannic acid, a ubiquitous compound found in plants, and poly(ethylene) glycol, yielding a 2.5 times greater water-resistant adhesion compared with commercial fibrin glue.

Abstract

This video describes the simplest protocol for preparing biodegradable surgical glue that has an effective hemostatic ability and greater water-resistant adhesion strength than commercial tissue adhesives. Medical adhesives have attracted great attention as potential alternative tools to sutures and staples due to their convenience in usage with minimal invasiveness. Although there are several protocols for developing tissue adhesives including those commercially available such as fibrin glues and cyanoacrylate-based materials, mostly they require a series of chemical syntheses of organic molecules, or complicated protein-purification methods, in the case of bio-driven materials (i.e., fibrin glue). Also, the development of surgical glues exhibiting high adhesive properties while maintaining biodegradability is still a challenge due to difficulties in achieving good performance in the wet environment of the body. We illustrate a new method to prepare a medical glue, known as TAPE, by the weight-based separation of a water-immiscible supramolecular aggregate formed after a physical mixing of a plant-derived, wet-resistant adhesive molecule,Tannic Acid (TA), and a well-known biopolymer, Poly(Ethylene) glycol (PEG). With our approach, TAPE shows high adhesion strength, which is 2.5-fold more than commercial fibrin glue in the presence of water. Furthermore, TAPE is biodegradable in physiological conditions and can be used as a potent hemostatic glue against tissue bleeding. We expect the widespread use of TAPE in a variety of medical settings and drug delivery applications, such as polymers for muco-adhesion, drug depots, and others.

Introduction

In a past decade, efforts have been made to replace current surgical sutures and staples to close wounds with biodegradable/bioabsorbable adhesives due to their convenience in usage and low tissue invasiveness during surgical treatments. Commercially available tissue-adhesives are classified into four types: (1) cyanoacrylate derivatives1, (2) fibrin glues formed by enzymatic conversion from fibrinogen to fibrin polymers by thrombin2,3, (3) protein-based materials such as chemically or physically cross-linked albumin and/or gelatin4,5, and (4) synthetic polymer-based ones6. Although they have been used in many clinical appli

Protocol

All animal care and experiments are performed in accordance with the ethical protocol provided by the KAIST (Korea Advanced Institute of Science and Technology) IRB (Institutional Review Board).

1. TAPE Formation

  1. For preparing a TA solution, place a 4 ml-sized glass vial on a magnetic stirrer, and add 1 ml of distilled water with a stirring bar. Add 1 g of tannic acid to the vial, and dissolve it in the water by gentle stirring at 200 rpm for more than 1 hr. When the TA is completely dissolved, the mixture becomes transparent with a brown color.
  2. Prepare a PEG solution by adding 1 g of PEG powder (4-arms, 10 kDa, and linear, 4.6 kDa) to 1 m

Results

TAPE is a supramolecular aggregate that settles down after centrifuging the mixture of two aqueous solutions containing TA (1 g/ml in distilled water) and PEG (1 g/ml in distilled water) with 2:1 volume ratio (Figure 1A). The mixing ratio is the key factor in achieving high adhesion strength; when TAPE is formed by a 2:1 mixing ratio, 20 units of the hydroxyl group (-OH) in 25 units of TA interact with each ether group (-O-) in PEG, resulting in the highest intermolecular...

Discussion

We developed an entirely new class of hemostatic adhesive named TAPE inspired by the water-resistant molecular interaction of a plant-derived polyphenolic compound, TA. TA is a representative hydrolysable tannin that has significantly attracted attention due to its anti-oxidant, anti-bacterial, anti-mutagenic, and anti-carcinogenic properties.

The process of making TAPE is extremely simple, scalable, and environmentally friendly, as it is just the one-step mixing of two aqueous solutions follo...

Disclosures

The authors have nothing to disclose.

Acknowledgements

This study was supported by National Research Foundation of South Korea: Mid-career scientist grant (2014002855), and Ministry of Industry, Trade, and Natural Resources: World Premier Material Development Program. This work is also supported by in part by Center for Nature-inspired Technology (CNiT) in KAIST Institute for NanoCentury (KINC).

Materials

NameCompanyCatalog NumberComments
Tannic acidSigma-aldrich403040
Poly(ethylene oxide), 4-arm, hydroxy terminatedAldrich565709Averge Mn ~ 10,000
Poly(ethylene glycol)Aldrich373001Average Mn 4,600
Biopsy punchMiltex33-36Diameter = 6 mm
Aron AlphaToagosei Co., Ltd.Instant glue
Universal testing machine (UTM)Instron5583
Microcentrifuge tubesSPL life science600151.5 ml
Petri dishSPL life science1009090 x 15 mm
Sodium phosphate monobasicSigmaS50111x PBS ingredient
Sodium phosphate dibasicSigmaS51361x PBS ingredient
Sodium chlorideDuchefa biochemieS0520.50001x PBS ingredient
Incubating shakerLab companionSIF6000R
ICR miceOrient bioNormal ICR mouse6 weeks, 30 - 35 g, male
Tiletamine-zolazepam (Zoletil 50)Virbac
Zylazine (Rompun)Bayer
PrecisionGlideTM needle (18 G)BD30203218 G
Filter paperWhatman1001 125Diameter = 125 mm
ParafilmBemis Flexible PakagingPM996

References

  1. Leggat, P. A., Smith, D. R., Kedjarune, U. Surgical applications of cyanoacrylate adhesives: a review of toxicity. ANZ J Surg. 77 (4), 209-213 (2007).
  2. MacGillivray, T. E. Fibrin Sealants and Glues. J Cardiac Surg.

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TAPEBiodegradable Hemostatic GlueSurgical ApplicationTannic AcidPEGAdhesive StrengthTissue AdhesiveSealantPorcine Biopsy SkinCyanoacrylate GlueForce distance CurveWater Resistance

TAPE: A Biodegradable Hemostatic Glue Inspired by a Ubiquitous Compound in Plants for Surgical Application (2025)
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