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1Bio/Polymer Research Group, School of Biotechnology & Biomolecular Sciences, University of New South Wales
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The fabrication of a novel, flexible thin film surgical adhesive from FDA approved ingredients, chitosan and indocyanine green is described. Bonding of this adhesive to collagenous tissue through a simple activation process with a low-powered infra-red laser is demonstrated.
Foster, L. J. R., Karsten, E. A Chitosan Based, Laser Activated Thin Film Surgical Adhesive, 'SurgiLux': Preparation and Demonstration. J. Vis. Exp. (68), e3527, doi:10.3791/3527 (2012).
Sutures are a 4,000 year old technology that remain the 'gold-standard' for wound closure by virtue of their repair strength (~100 KPa). However, sutures can act as a nidus for infection and in many procedures are unable to effect wound repair or interfere with functional tissue regeneration.1 Surgical glues and adhesives, such as those based on fibrin and cyanoacrylates, have been developed as alternatives to sutures for the repair of such wounds. However, current commercial adhesives also have significant disadvantages, ranging from viral and prion transfer and a lack of repair strength as with the fibrin glues, to tissue toxicity and a lack of biocompatibility for the cyanoacrylate based adhesives. Furthermore, currently available surgical adhesives tend to be gel-based and can have extended curing times which limit their application.2 Similarly, the use of UV lasers to facilitate cross-linking mechanisms in protein-based or albumin 'solders' can lead to DNA damage while laser tissue welding (LTW) predisposes thermal damage to tissues.3 Despite their disadvantages, adhesives and LTW have captured approximately 30% of the wound closure market reported to be in excess of US $5 billion per annum, a significant testament to the need for sutureless technology.4
In the pursuit of sutureless technology we have utilized chitosan as a biomaterial for the development of a flexible, thin film, laser-activated surgical adhesive termed 'SurgiLux'. This novel bioadhesive uses a unique combination of biomaterials and photonics that are FDA approved and successfully used in a variety of biomedical applications and products. SurgiLux overcomes all the disadvantages associated with sutures and current surgical adhesives (see Table 1).
In this presentation we report the relatively simple protocol for the fabrication of SurgiLux and demonstrate its laser activation and tissue weld strength. SurgiLux films adhere to collagenous tissue without chemical modification such as cross-linking and through irradiation using a comparatively low-powered (120 mW) infrared laser instead of UV light. Chitosan films have a natural but weak adhesive attraction to collagen (~3 KPa), laser activation of the chitosan based SurgiLux films emphasizes the strength of this adhesion through polymer chain interactions as a consequence of transient thermal expansion.5 Without this 'activation' process, SurgiLux films are readily removed.6-9 SurgiLux has been tested both in vitro and in vivo on a variety of tissues including nerve, intestine, dura mater and cornea. In all cases it demonstrated good biocompatibility and negligible thermal damage as a consequence of irradiation.6-10
1. Preparation of SurgiLux Solution
2. Casting of SurgiLux Films
3. Laser Activation of SurgiLux Adhesive Films
4. Strength of the Repair
Centrifugation leads to a transparent green solution, which increases viscosity after storage at 4-6 °C. After standing for 3 weeks, the green solution is converted into a transparent green SurgiLux film approximately 20 microns thick and, as demonstrated in the video, is readily flexible.
Upon irradiation with the laser, the SurgiLux film bonds to the tissue. This can be observed at the edges of the film where the tissue appears to contract as the laser beam passes over the film (Figure 2). No charring or ablation of the tissue and film should be observed. The bonding strength of SurgiLux to the tissue should be sufficient to lift the bisected pieces of tissue, and when the tensile strength is measured should be approximately 15 KPa for the test reported here.
Table 1. Comparison of properties for proposed SurgiLux system and commercially available fibrin and cyanoacrylate surgical adhesives.
Figure 1. Diagrammatic illustration of the SurgiLux thin film adhesive fabrication and activation process; corresponding to the protocol text. Click here to view larger figure.
Figure 2. Photograph (x20) showing the thin SurgiLux film after laser activation adhered to bovine intestine tissue and 'contracting' into the tissue incision (TA, TB: separate pieces of tissue, I: incision, S: SurgiLux film).
Figure 3. Graph showing tissue adhesion strengths for various adhesives: Chitosan and SurgiLux films applied on tissue, Tisseel (fibrin) and Histoacryl gels (cyanoacrylate) applied on tissue.
Figure 4. Scanning Electron Micrographs (SEMS) illustrating cells attached to SurgiLux films; human cell lineages (a) olfactory ensheathing cells [x1.5k], (b) stromal fibroblasts [x500], and (c) skeletal muscle derived satellite stem cells [x1.7k]. Click here to view larger figure.
Figure 5. Graph showing the change in film thickness with increasing SurgiLux solution casting volume (ml) and a constant casting area (7.09 x 103 mm2).
Figure 6. Scanning Electron Micrograph (SEM) of film showing the presence of 'nipples' (SN) protruding from the surface (S).
Chitosan can be obtained in a variety of molecular weights and with different degrees of deactylation (DDA). Variations in chitosan purity may lead to the presence of particulates in the SurgiLux solution; centrifugation is used to eliminate these and should result in a transparent green solution. However, filtration can also be used as an added or alternative fabrication step. As with any materials processing, variations, such as chitosan DDA and molecular weight, have implications for the physiochemical, biological and material properties of the resulting SurgiLux films, including the strength of its bonding to tissue.
The fabrication process for SurgiLux allows for considerable variation. For example, changes to the ratio of solution volume to casting surface area (ml:mm2) can be utilized to adjust the film thickness. Figure 5 shows a linear increase in the thickness of final SurgiLux films as the volume of solution poured into the Petri dish was increased. Similarly, modifications to the casting surface can be used to modify the film's surface morphology. Figure 6 shows the presence of micron-sized 'nipples' on the surface of SurgiLux film. Such templating techniques can be utilized to produce various surfaces to improve tissue adhesion, prevent microbial cell attachment and promote tissue reintegration.11 Furthermore, various biologically active agents can be incorporated into the fabrication process to produce an adhesive film for regional drug delivery.10
Table 1 summarizes the advantages of this SurgiLux thin film adhesive system compared to conventional fibrin and cyanoacrylate adhesives. While the strength of tissue repair is less than sutures, SurgiLux avoids the numerous disadvantages of this traditional wound closure technique as well as the current favored commercial surgical adhesives.
The ability of SurgiLux to bond various collagenous tissues combined with its material flexibility suggest its potential in laparoscopy, while the versatility of the fabrication process promotes its further development for applications in tissue engineering and regenerative medicine.
No conflicts of interest declared.
The authors acknowledge a grant from the National Health and Medical Research Council of Australia (NHMRC #1000674) to L.J.R. Foster.
|Indocyanine Green||Sigma-Aldrich||I2633||Also known as Cardiogreen|
|Infra-red diode laser with fiber delivery. (808 nm, 120 mW, Beam core 200 μm)||CNI Lasers||Fc-808||Variable system up to 5 W power|
|Laser safety glasses||CNI Lasers||LS-G|
|Tensile testing apparatus||Instron Pty Ltd||5542||50 N load cell|
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