Scientists supported by NIBIB have created laser-activated nanomaterials that have the ability to integrate with wounded tissues to form seals that are excellent than sutures in containing body fluids and preventing bacterial infection.
Sealant processing requires isolation of silk from cocoons, creation of silk solution, and addition of gold nanorods (GNR). The silk-GNR mix is formed into a silk-GNR film. The gold nanorods dispersed in the silk film are shown on the right. (Image credit: Urie et al. Adv. Funct. Mater., 2018)
It is conventional to perform tissue repair during surgery or following injury using sutures and staples, which could lead to tissue damage and complications, such as infection. In order to address some of these problems, adhesives and glues have been created. However, these adhesives and glues can result in fresh issues such as poor adhesion, toxicity, and inhibition of the body’s natural healing processes, like cell migration into the wound space.
At present, scientists funded by NIBIB at Arizona State University are creating an innovative sealant technology that appears to be somewhat like science fiction—laser-activated nanosealants (LANS).
LANS improve on current methods, because they are significantly more biocompatible than sutures or staples,” explained David Rampulla, PhD, director of the NIBIB program in Biomaterials. “ Increased biocompatibility means they are less likely to be seen as a foreign, irritating substance, which reduces the chance of a damaging reaction from the immune system.”
Yet, biocompatibility is not so simple. The Arizona team has created this technology by cautiously selecting and testing the materials used in the sealant and even the particular type of laser light required to activate the sealant without resulting in heat-induced collateral tissue damage.
The sealant is made using biocompatible silk embedded with tiny gold particles known as nanorods. The gold nanorods are heated by the laser to activate the silk sealant. Upon being activated, the silk nanosealant acquires unique properties that make it to gently traverse into or “interdigitate” with the tissue proteins to form a sturdy seal. Gold was used due to its property of quickly cooling after laser heating, thereby reducing any peripheral tissue damage upon prolonged heat exposure.
Two types of disk-shaped LANS were developed. One is water-resistant for application in liquid environments, for example, during surgery to remove a section of cancerous intestine. It is necessary for the sealant to work in a liquid environment to reattach the ends of the intestine. A leak-proof seal is crucial to make sure that bacteria in the intestine do not leak into the bloodstream, which can lead to serious blood infection called sepsis.
Testing of the water-resistant LANS was performed by using them for repair of samples of pig intestine. In contrast to glued and sutured intestine, the LANS exhibited superior strength during tests of burst pressure, evaluated by pumping fluid into the intestine. Particularly, the potential of the LANS to contain liquid under pressure was analogous to uninjured intestine and seven times stronger when compared to sutures. Moreover, LANS prevented the leakage of bacteria from the repaired intestine.
The second LANS type blend with water to form a paste that can be applied to superficial wounds on the skin. Testing of this LANS type was performed by using it to repair a mouse skin wound and comparing it with both skin repaired with an adhesive glue and sutured skin. The LANS were formed into a paste, applied to the skin cut, and activated using the laser around the margins of the sealant.
Two days after being applied, the LANS led to considerable increase in skin strength than the sutures or glue. Moreover, the skin had fewer cellular debris and neutrophils, suggesting that there was very less immune reaction to the LANS.
Our results demonstrated that our combination of tissue-integrating nanomaterials, along with the reduced intensity of heat required in this system is a promising technology for eventual use across all fields of medicine and surgery,” stated Kaushal Rege, PhD, Professor of Chemical Engineering at Arizona State and the senior author of the study. “ In addition to fine-tuning the photochemical bonding parameters of the system, we are now testing formulations that will allow for drug loading and release with different medications and with varying timed-release profiles that optimize treatment and healing.”
The research was published in
Advanced Functional Materials. The study was supported by grant EB020690 from the National Institute of Biomedical Imaging and Bioengineering, and the Department of Defense, Air Force Office of Scientific Research.