(67c) Photothermal Welding of Ruptured Intestinal Tissue Using Plasmonic Nanocomposites
Each year, over 600,000 patients undergo surgical operations to treat colorectal diseases in the United States (www.sages.org). Anastomotic leakage following standard colorectal anastomosis is commonly associated with life-threatening bacterial infections (incidence rate: 4-17%). The purpose of this study is to demonstrate that plasmonic nanocomposites, generated from gold nanorods and elastin-like polypeptides, can facilitate the photothermal welding of ruptured colorectal tissues. We hypothesized that heat transfer from the light-activated nanocomposite will facilitate the binding of ruptured tissue and result in a fluid-tight seal. We test our hypothesis using ex-vivo porcine intestines.
Gold nanorods (GNRs) and cysteine-containing elastin-like polypeptides (CELPs) were synthesized by adapting procedures from literature. Nanocomposites (1 mm diameter, ~250 μm thick) were prepared by two steps: (i) self-assembly of CELPs (2 mg/ml) on GNRs (9.5-190 μg/mL) via gold-thiol bonds to form dispersed GNR-CELP nanoassemblies at 4°C and (ii) irreversible phase separation of nanoassemblies to form solid-phase nanocomposites at 37°C. The optical and rheological properties of the nanocomposites were measured by UV-Vis spectroscopy and rheometer, respectively. The biological properties of the nanocomposites were evaluated using murine fibroblast cells. A titanium sapphire laser pumped by a solid-state laser (Spectra-Physics, Millennia) was employed for welding (800 nm, 20 W/cm2, 0.4-2.8 kJ) of the ruptured porcine small intestines (Animal Technologies Inc.) in presence and absence of nanocomposites. Tissue tensile strength, leakage pressure, bursting pressure and bacteria (E. coli DH5-alfa) leakage were measured immediately post-photothermal welding.
We have delivered reproducible, stable, light-activable, and biocompatible GNR-CELP nanocomposites; the swelling ratio and the stiffness of the nanocomposite can be modulated by adjusting the GNR content (0-8.7 wt%). We observed that fibroblast cells could proliferate with minimal cytotoxicity (<10% cell death) on top of the nanocomposites up to 72h of culture. Photo-activation of nanocomposites resulted in a tissue temperature increase up to ~60°C, which enhanced the tensile strength and leaking pressure of the ruptured-tissue up to 47% and 78% of its original intact form, respectively.
The plasmonic nanocomposites possess tremendous translational potential in the repair of intestinal and colorectal tissues in several diseases, including cancer. The use of therapeutically relevant cells, including stem cells, and encapsulation of drugs within the nanocomposite to further enhance healing and repair (while preventing infection) will be further investigated and discussed.