Porous and soluble adhesives based on chitosan for photochemical tissue bonding

Abstract

Background: Photochemical tissue bonding with standard chitosan films containing rose bengal (0.01 % w/v) and chitosan (MW ~ 250 kDa, 1.7 % w/v) is an experimental technique for tissue repair that avoids thermal injuries and the use of sutures. In this study, innovative formulation and fabrication procedures were adopted to improve the film's bonding strength, degradation rate and ability to integrate with tissue. Materials and Methods: Films were fabricated using two blends of oligomeric chitosan (MW ~ 5 kDa) and medium MW chitosan (~ 250 kDa) at 10 % or 30 % ratio. The chitosan blends were dissolved in a water solution of acetic acid (2 % v/v) and rose bengal (0.01 % w/v). Other films were prepared using the blends described above with the addition of the amino acid L-3,4-dihydroxyphenylalanine (L-DOPA) at a concentration of 0.16 % w/v. The films were further processed making them porous by freeze drying. Non-porous films were also fabricated with oligomeric chitosan at 10 % and 30 % ratio, with and without L-DOPA for comparison. Films were bonded in vitro to sheep intestine using a light emitting diode (LED, ? = 515 nm) to test their adhesion strength with a single column tensiometer. Mechanical and physical properties of the films were also assessed, such as tensile strength, percentage elongation, Young's modulus, mass loss over a 7-day period and swelling over a 2-hour period in physiological conditions. Results: The porous adhesive films with L-DOPA and 10 % oligomeric chitosan (pore diameter = 110 ± 24 µm), produced the highest tissue bonding strength of 19.0 ± 1.1 kPa (n = 30, p values < 0.0001, one-way ANOVA, Tukey's post-test), which was about 30 % stronger than standard chitosan films. The percentage mass loss of the films at day 7 increased from 5 to 60 % as their oligomeric content increased from 0 to 30 %. Porous films without L-DOPA had tensile strengths (0.1 - 1.1 MPa) and Young's moduli (0.5 - 1.6 MPa) that were 20 to 40 % of their non-porous counterparts. Nevertheless, the bonding strength of these porous films was high (10 - 15 kPa) and thus still suitable for soft tissue applications. Noticeably, the porous films had higher swelling ratios than non-porous films (220 - 320 % vs 95 - 110 %). Conclusion: Porous films with L-DOPA and 10 % oligomeric chitosan have been successfully fabricated and tested in vitro. These films have higher tissue bonding strengths than standard chitosan adhesives when photoactivated and their porosity and erodibility can facilitate tissue integration.

Date of Award	2019
Original language	English