A Characterization Scheme to Assess the Heating Performance of Developed Biological Solders for Laser Tissue Welding

Abstract

Laser tissue welding (LTW) is an alternative, suture-less wound closure technique. It involves positioning opposite wound edges in close proximity, followed by near-infrared laser irradiation until a temperature of approximately 60°C is reached. At this temperature, protein interdigitation and tissue coagulation occur, resulting in a re-homogenized continuous tissue matrix. Heat localization at the site of joining is essential to produce strong tissue bonds while minimizing thermal damage to the surrounding region. One method to achieve heat localization is through the administration of photothermally responsive biological solders (biosolders).

For the presented work, nanocomposite gels (NCGs) were developed as biosolders. They were prepared by dissolving hyaluronic acid (HA) and guar gum (GG) to a final polymeric concentration of 3% w/v in aqueous solutions with up to 1.4 nM gold nanorods (GNRs). The addition of GG was found to stabilize GNR dispersion through the gel and enhance their heat generation under laser irradiation. To assess the clinical relevance of the gel formulations, a simplified photothermal characterization scheme was developed. The method relies on a custom-built measurement system that can confine gel samples to clinically relevant thicknesses as thin as 100 μm. This setup was used to measure temperature increases (ΔT) of gel specimens with and without GNRs, with a repeatability of ΔT = 0.123°C.

A plasmonic heat amplification factor, ξ , is proposed as a new safety metric for assessing the clinical relevance of a biosolder formulation. It is defined as the ratio of ΔT for an NCG by ΔT of its corresponding control gel. A subset of the developed NCG formulations were found to possess ξ >1.3, indicating their thermal suitability for safe LTW. The presented method aims to establish a new standard foundation for the temperature monitoring of laser-irradiated gels in isolation, allowing for the cost-effective screening of preliminary NCG formulations for eventual administration to tissue models.

The developed photothermal characterization system was further used to determine the photothermal conversion efficiency, or fraction of heating power per absorbed light, η, of developed NCGs. Although a standardized method for determining η in liquid photothermal solutions has been previously proposed, it is unsuitable for semisolid materials such as viscous gels that are considered for medical applications like LTW. As such, a simple, yet robust approach is proposed for estimating η of viscous photothermal gels via the direct determination of thermal conductance. The method allows for more confident reports of η for optimizing the photothermal response of photoresponsive materials.