A Biodegradable and Biocompatible Gecko-Inspired Tissue Adhesive

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Original entry by A.J. Kumar, APPHY 225 Fall 2009

Reference

Alborz Mahdavi, Lino Ferreira, Cathryn Sundback, Jason W. Nichol, Edwin P. Chan, David J. D. Carter, Chris J. Bettinger, Siamrut Patanavanich, Loice Chignozha, Eli Ben-Joseph, Alex Galakatos, Howard Pryor, Irina Pomerantseva, Peter T. Masiakos, William Faquin, Andreas Zumbuehl, Seungpyo Hong, Jeffrey Borenstein, Joseph Vacanti, Robert Langer, and Jeffrey M. Karp. PNAS 2008 105 (7), 2307-2312.

Keywords

Chemical Cross-Link, Medical adhesive, Nanotopography, Surgical suture, Polymers, Adhesion

Summary

In this paper, the authors describe a biodegradable and biocompatible gecko-inspired tissue adhesive that they have created using nano-patterned polymers. The feet of geckos have been of great interest to scientists exploring interface forces. The feet of geckos are covered in a dense fibrillar array which exploits a combination of van der Waals and capillary forces to adhere to surfaces. Several groups have done work to develop gecko-inspired tapes for various applications. The authors of this paper look specifically at the advantages these kinds of tapes can offer in a medical setting. Gecko-inspired tapes could be a useful surgical suture. In traditional sutures such as stapling or stitching, the tissue must be punctured to put in the suture. With a tape, very little if deformation to the underlying tissue would be required. Additionally, such an adhesive could have applications as waterproof sealants for hollow organ anatomoses, mesh grafts to treat hernias, ulcers and burns, and hemostatic wound dressing.

In addition to the creation of adhesion forces, this tape has the requirement to be both biocompatible and biodegradable. If the tape is to be used in vivo it obviously needs to be bio-compatible. If the tape is to be used to be used to help suture cuts after surgery, it should be biodegradable so that after the wound is healed, the suture degrades and is passed out of the body.

Figure 1: Development of biodegradable synthetic gecko patterns. (a) Nanomolding of the PGSA prepolymer is accomplished by photocuring the prepolymer under UV light followed by removal of the pattern and subsequent spin coating of DXTA on the surface of the pillars. SEM demonstrated excellent pattern transfer and fidelity. (b) Gecko patterns having different pillar size and center to center pitch were developed as illustrated by theSEMimages. Pillar dimensions were measured by using optical profilometry as represented by the bar graphs, with red representing the height of pillars; black, the center to center pitch; light gray, diameter of pillar base; and dark gray, diameter of the tip. (Small and large scale bars, 1 and 10 <math>\mu</math>m, respectively.) (c) Adhesion trend of the longest pillar heights (2.4 <math>\mu</math>m) shows adhesion of nanopattern with respect to flat polymer as a function of ratio of tip diameter to pitch. R2 value of linear fit is 0.99. (d) Adhesion trend of the patterns is plotted as a function of ratio of tip diameter to base diameter of pillars. R2 values of linear fit for the low- and high-pitch patterns are 0.96 and 0.99, respectively.


To create such a material, the authors turn to polymers and nano-patterning. The elastic properties of polymers offer an additional advantage since they will then be more biocompatible with naturally elastic soft materials of the body. Specifically, the authors use poly(glycerol sebacate acrylate) (PGSA). First, they lay down a flat surface of the polymer and then they pattern nano-pillars on top of the surface. The pillars were conical in nature and the adhesion was measured as a function of the ratio of the tip diameter and the base diameter. The authors then measured adhesion of these surfaces and found that the nano-patterned surfaces led to a two-fold increase in adhesion over a flat surface of the polymer. To optimize for tissue interfacing, the authors then coated the nano-patterned surface with a thin layer of oxidized dextran (DXT) which has functionalized aldehydes (DXT aldehyde is DXTA). The DXTA reacts with proteins to form an imine (type of double bond). Different compositions of PGSA were tested, including some with a mixture of polyethylene glycol diacrylate (PEGDA). From what I understand, the PEGDA and DXTA create cross-links with the tissue and hence allow the adhesion to form in an aqueous environment, a requirement that is crucial for the wet environment of a body.

Figure 2: DXTA coating of nanopatterned PGSA polymer improves tissue adhesion in vitro. (a–c) Relative adhesion of nanopatterned vs. unpatterned PGSA polymer to porcine tissue slides as a function of DXTA surface coating concentration. A represents PGSA DA=0.8, B is PGSA DA=0.3 with5%PEGDA, and C is PGSA DA=0.3. Data were normalized to the unpatterned DA = 0.8 PGSA polymer without DXTA coating. (d) Normalized adhesion results of the PGSA DA = 0.3 with 5% PEG DA shows the effect of washing on improving adhesion at various DXTA concentrations. (e) Nanopatterned PGSA polymer after surface spin coating with water as control. (F and G) Nanopatterned PGSA after surface spin coating with 0.05% DXTA solution shows adhesion of neighboring pillar tips. The black arrow indicates how DXTA polymer may cause neighboring pillar tips to stick together. (h) Five percent DXTA completely obstructed the underlying nanopattern. (i) The baseline adhesion and maximum values obtained for each material used.

The authors go on to characterize the material and demonstrate that it is successful as an adhesive in both in vitro and in vivo settings. In conclusion, they have created a polymer based, nano-patterned material that is adhesive while meeting the requirements of biocompatibility and biodegradibility.

Soft Matter Connection

This paper demonstrates some of the great potential that lies in soft matter. The paper is about the problem of creating interface forces between two different soft materials (a polymer compound and living tissue). As described above, soft matter that is biodegradable and biocompatible could offer advantages over traditional surgical sutures.

From the polymer end, this paper demonstrates some of the interesting properties of polymers, such as elasticity and cross-linking, that can be exploited in materials applications. With regards to interface forces, the gecko-inspired nature of the material naturally leads to questions about the van der Waals and capillary forces involved on the surface of this material. Though data is presented on relative adhesion, I did not find a thorough characterization or analytical discussion of the surface forces in this paper. It would be interesting to try and model the system to see what force scales are actually relevant from resulting van der Walls and capillary forces.

Additional References

[1] Basic info and source of PEGDA

[2] Wikipedia article on imines