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Bioinspired hybrid polymer scaffold regenerates and repairs mouse kidney

By Stephen Riffle April 25, 2019
bioinspired scaffold
(a) Schematic of a conventional poly(lactide-co-glycolide) (PLGA) scaffold that inhibits tissue regeneration due to the inflammatory reaction and fibrosis caused by the acidic microenvironment formed during the degradation process; and (b) bioinspired scaffold that neutralizes the acidic microenvironment through the Mg(OH)2 to inhibit the inflammatory response. The latter shows good cytocompatibility by the decellularized extracellular matrix on a surface of the scaffold. Credit: ACS Central Science

Scaffolding in the context of tissue engineering describes materials—often made from ceramic, synthetic or natural polymers—that augment tissue growth and regeneration. Such materials function by giving damaged tissue some combination of structural, biochemical, and mechanical influences over cell behavior. In a study published in a recent issue of ACS Central Science, lead author Eugene Lih at the Korea Institute of Science and Technology (KIST) and co-authors describe the use of a composite scaffolding—a porous structure made of both synthetic and natural polymers—to enable regrowth of a damaged mouse kidney. Their research is built on the idea that damaged organs could be repaired through the use of scaffolds that are specifically designed to recreate the materials properties of the healthy organ, sometimes referred to as bioinspired scaffolds.  

Lih and colleagues—from KIST, CHA University, Sogang University, Kyungpook National University, and the University of Chicago—made use of a synthetic polymer, poly(lactide-co-glycolide) (shortened to just PLGA), which has been used for decades in medical applications such as sutures, bone plates, and drug delivery vehicles. PLGA is a simple and widely used synthetic polymer consisting of lactic acid (LA) and glycolic acid (GA)—the ratio of which can be altered to customize PLGA’s strength, flexibility, and degradation rate. 

Though favored in many applications, the use of PLGA in organ regeneration is limited due to its effects on the cellular microenvironment. The area between cells can be a busy place where cellular waste, proteins, oxygen, sugars, and other chemicals are present. It is important that cells maintain control over the extracellular space because even small fluctuations in the pH or oxygen levels, for example, can result in cell death, inflammation and clinical failure. Scaffolds function, in part, by helping injured tissues form a balanced extracellular space, with the right combination of buffers and growth factors, to allow for healthy tissue regeneration.  However, degradation of some polymers, including PLGA, can lead to the toxic buildup of acidic compounds, such as lactic acid. For this reason, PLGA has historically not been favored for tissue regeneration. 

This may change with the work of Lih and colleagues. To form their composite scaffolds, the researchers included two additional components aside from PLGA: decellularized extracellular matrix and Mg(OH)2. The decellularized extracellular matrix, taken from porcine kidneys, recreates important structural, chemical, and biological aspects of the kidney extracellular microenvironment and may also help to buffer the accumulation of acidic byproducts. Mg(OH)2 could help neutralize the acidic hydrogen atoms that result from PLGA breakdown. 

Through a combination of biochemical and physiological demonstrations, the research team showed that this composite polymer is a viable scaffold that enables significant regeneration of damaged mouse kidneys, far beyond what is observed without the scaffolding. The implanted scaffold was replaced by the mouse kidney tissue quickly, and the damaged kidney regained full functionality. 

Philip Lewis, a researcher working on in vitro organ development systems at Cincinnati Children’s Hospital, finds the research to be “very, very thorough” and remarks that it is a novel use of old materials. “A lot of people think the story is over and that we’ve done everything we can with [PLGA]. Use of the individual components isn’t particularly novel, but the use of each of them together is,” Lewis says. 

The application of this polymer to tissue regeneration is a powerful contribution to the field, in part for its simplicity. Many times development of new materials comes with complex methods that are challenging to replicate. However, the extracellular matrix, Mg(OH)2, and PLGA composite scaffolding is relatively simple and may be easily adapted by other laboratories. This simplicity, along with the significance of showing that scaffolding can be designed to neutralize the negative effects of materials degradation, reveals some exciting new possibilities for regenerative medicine. Specifically, Lih and his colleagues suggest these results may enable the development of advanced implants, grafts, and other biomedical devices consisting of biodegradable materials like PLGA.    

Read the article in ACS Central Science.