A better understanding of lung tissue repair mechanics 

Researchers from the BioNanomaterials group at the Adolphe Merkle Institute have developed a method that more accurately mimics injury and wound healing response in lung epithelial tissues than previous models. Besides providing additional knowledge about regeneration after injury, this method should lead to a better understanding of how specific nanomaterials affect cell mechanics during tissue repair.

The number of in vitro and in vivo toxicity studies of nanomaterials has increased dramatically in recent years. Unfortunately, the availability of information regarding the alteration of cell mechanics in the presence of nanomaterials is still limited. These cell mechanics are critical indicators for cell functionality and health, and these processes drive important biological activities such as cell migration, differentiation, wound healing, and tissue integrity.

Wound healing assays are one method used exten-sively to study tissue repair mechanisms; they are typically performed by physically scratching cells to create an open space in which living cells can lodge. Yet, this is not necessarily a true reflection of what happens in real life. This method is, for example, unsuitable for studying the repair response of tissue at a small injury site where dead cells are still present. The researchers from the AMI BioNanomaterials group chose another approach by inflicting damage on a specific zone of lung epithelial tissue using photobleaching, and leaving any potential dead cells in place. “What is novel is that we took a method that was pre-existing, but that had never been used before for this type of application,” explains Dr. Dedy Septiadi. This extensive photobleaching was performed by illuminating certain cell areas with a high-power ultraviolet laser in a confocal microscopy setup, and then sufficiently inducing a specific cell death mechanism, namely, apoptosis. “Our method is relatively efficient,” adds Septiadi. “Much of the challenge was defining the correct parameters to carry out our experiments.”

The AMI researchers found that individual healthy epithelial cells are able to clear the dead cells by pushing them to one side. Then, macrophages, the body’s cellular cleaning crew, actively swallow cellular debris, creating an empty space. However, the push repair mechanism is hampered when carbon nanotubes (CNTs) with a high stiffness are introduced, suggesting CNTs can interfere with lung repair, either by delaying or hindering wound recovery. Exposure to high aspect ratio nanomaterials such as these nanotubes has been shown to induce cell death and micro-injuries in epithelial lung tissue, potentially leading to pulmonary scarring (fibrosis). The AMI research could therefore also help understand the impairment or repair mechanism induced by CNTs in a wound healing context. “Our work is focused purely on the mechanics involved,” says Septiadi. “But the biological impact of CNTs is being investigated by our group separately to increase the scope of our research.”

This study, the results of which were published in the leading scientific journal Advanced Materials are part of a wider effort undertaken by the AMI BioNanomaterials group under the leadership of group co-chair Professor Barbara Rothen-Rutishauser to comprehend wound healing at the mechanistic level, which is difficult to do in in vivo situations.  “It is important to understand the potential impact of inhaled CNTs, especially in an occupational setting,” explains Rothen-Rutishauser. “With our research, we can help to understand pathophysiological processes in lung tissue during wound repair and how this is impacted by nanomaterials.”

Reference: Septiadi, D., Abdussalam, W., Rodriguez-Lorenzo, L., Spuch-Calvar, M., Bourquin, J., Petri-Fink, A., Rothen-Rutishauser, B. Bio-nanomechanics: Revealing the Role of Epithelial Mechanics and Macrophage Clearance during Pulmonary Epithelial Injury Recovery in the Presence of Carbon Nanotubes, Adv. Mater., 2018, 30, 1870396