A Chitosan Based, Laser Activated Thin Film Surgical Adhesive, 'SurgiLux': Preparation and Demonstration

Summary

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.

Abstract

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

Protocol

1. Preparation of SurgiLux Solution

1. Prepare a 2% (v/v) solution of acetic acid using deionized water in a clean glass beaker; use a laminar flow hood to avoid contamination.
2. Weigh 0.02% (w/v) of the chromophore, indocyanine green, ICG, in a sterile Eppendorf tube; ensure the tube is wrapped in silver foil to prevent any light penetration.
3. Using a clean, disposable pipette, transfer approximately 1 ml of the dilute acetic acid solution to the tube to dissolve the dye, shake gently and keep wrapped in foil.
4. Transfer the solubilized ICG into the beaker and add 2% (w/v) of chitosan powder before adding a sterile magnetic stirrer.<....

Results

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 (Figu.......

Discussion

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.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Chitosan	Sigma-Aldrich	448877
Indocyanine Green	Sigma-Aldrich	I2633	Also known as Cardiogreen
Acetic acid	Sigma-Aldrich	320099
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