The extracellular matrix, shown with a cross-section of a histotripsy lesion created in bovine liver tissue.
A University of Washington team has used sound waves to create cellular scaffolding for tissue engineering – a unique approach that could help overcome one of regenerative medicine’s significant obstacles.
The development emerged somewhat serendipitously. The Applied Physics Lab researchers had been studying boiling histotripsy, a method to destroy tissue with millisecond bursts of non-thermal ultrasound waves, to liquefy cancerous tumors.
The team was surprised at what remained after the process.
AP lab team
From left, Tanya Khokhlova, UW instructor of medicine; Yak-Nam Wang; and Vera Khokhlova, senior engineer in the Applied Physics Lab and principal investigator on the research.
picture of Tanya Khokhlova, Yak-Nam Wang and Vera Khokhlova
“Some of the stromal tissue and vasculature was being left behind,” said Yak-Nam Wang, a senior engineer. “So we had the idea about using this to decellularize tissues for tissue engineering and regenerative medicine.”
The structure that remains after decellularizing tissues is known as the extracellular matrix, a fibrous scaffold on which cells could grow. Most other methods for decellularizing tissues and organs involve chemical and enzymatic treatments that can damage the tissues and fibers and take multiple days. Histrostipsy suggests the possibility of fast decellularization of tissue with minimal damage to the matrix.
“In tissue engineering, one of the holy grails is to develop biomimetic structures so that you can replace tissues with native tissue,” Wang said.
With its bare composition, the extracellular matrix also induces only a relatively weak immune-suppresion response from the host. The matrix could then theoretically be fed with stem cells or cells from the same person to effectively regrow an organ.
“The other thought is that maybe you could just implant the extracellular matrix and then the body itself would self-seed the tissues, if it’s just a small patch of tissue that you’re replacing,” Wang said. “You won’t have any immune issues, and because you have this biomimetic scaffold that’s closer to the native tissue, healing would be better, and the body would recognize it as normal tissue.”
Wang is currently investigating decellularization of kidney and liver tissue from large animals. Future work involves increasing the size of the decellularized tissues and assessing their in-vivo regenerative efficacy.