Injectable photoreactive gel and biological adhesive help new cartilage grow

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Introduction

This is a production of the National Institute of Biomedical Imaging and Bioengineering, part of the National Institutes of Health

Host-Margot Kern: Every year, hundreds of thousands of Americans undergo surgery to repair torn hyaline cartilage—that is the tough, flexible tissue that acts as a shock absorber between bones. Yet, outcomes for cartilage repair are typically poor. The reason is that unlike other tissues in the body, cartilage lacks its own blood supply, which normally bathes damaged tissue and provide factors that promote regeneration.

Host-Margot Kern: Currently, the first-line therapy for cartilage repair is a technique called microfracture surgery in which tiny holes are drilled into the bone located directly below missing cartilage in order to release bone marrow into the damaged space. Because bone marrow contains a mixture of stem cells and blood, the  resulting clot provides an enriched environment that promotes cartilage regeneration.

Host-Margot Kern: Yet, only half of these surgeries are considered successful in the long-term. One issue is that the regenerated cartilage is a mixture of smooth hyaline cartilage and fibrous scar-like tissue. This fibrocartilage doesn’t function as well as pure hyaline cartilage as a cushion between joints.  Another issue is that the regenerated cartilage rarely integrates fully with the patient’s existing cartilage and this prevents it from becoming functional.

Host-Margot Kern: Dr. Rosemarie Hunziker is a program director in charge of overseeing NIBIB’s grant portfolio for tissue engineering. Over the years, she’s witnessed many attempts by doctors and researchers to devise novel techniques for cartilage repair.

Hunziker: I’ve seen just about everything from harvesting healthy cartilage from another part of the body and then directly transplanting it, although way through to complex formulations of scaffolds and cells grown in the lab and then implanted as a unit. The problem has always been, how to get the newly-generated tissue to integrate into a patients’ existing tissue so that it becomes functional.

Host-Margot Kern: But Dr. Jennifer Elisseeff, a tissue engineer at Johns Hopkins University, may have provided a promising new alternative. Elisseeff builds hyaline cartilage in her lab, a process that involves planting chondrocytes—which are cartilage-producing cells—into a biological scaffold and then incubating them in conditions similar to those found in the human body.  Elisseeff says choosing the right scaffold material is critical for producing high-quality cartilage.   

Elisseeff: As we’ve been learning more about biomaterials and how cells respond to them, we’ve also learned that chondrocytes, the cells that make up cartilage, prefer to be in a softer material as the tissue’s developing.

Host-Margot Kern: Elisseeff’s lab creates hydrogel scaffolds, which are smooth, flexible, and have a high water content. Not only do these hydrogels encourage the production of hyaline cartilage, but they also deter the development of unwanted tissue.

Elisseeff: We want to reduce scar formation and bone formation and these types of hydrogel scaffolds are able to do that. 

Host-Margot Kern: After several years of growing high-quality cartilage in the lab, Elisseeff predicted that if she could introduce her hydrogel scaffold into a patient following microfracture surgery, she might be able to influence the quality of the cartilage regenerated.

Host-Margot Kern: But implanting a scaffold into an irregularly shaped space where cartilage has broken off is no easy task. Even more difficult is getting the scaffold to adhere to the slippery walls of a patient’s surrounding cartilage, a step that’s crucial for the new cartilage to become functional.

Host-Margot Kern: With the support of NIBIB funding, Elisseeff began to develop two novel technologies to overcome these hurdles. The first was a photo-active hydrogel that could be injected as a liquid into an irregularly shaped cartilage defect and then solidified upon exposure to a light source.  The second technology was a biological adhesive that could bond to both the hydrogel and to specific proteins found on the surface of cartilage tissue, essentially cementing the scaffold in place.

Elisseeff: We wanted to be able to bond the hydrogel in tough environments, and then it also serves a biological role to help stimulate tissue development at that fragile interface.

Host-Margot Kern: Elisseeff’s photo-active gel and biological adhesive were recently tested in a clinical trial involving 18 patients.  Fifteen patients received microfracture with the gel/adhesive combo and three received microfracture alone.  

Host-Margot Kern: The growth of new cartilage was evaluated post-surgery using an innovative MRI technique, also developed by an NIBIB grantee, Dr. Gary Gold of Stanford Univeristy. The technique can distinguish between fibrous and smooth cartilage and gives doctors a way to monitor cartilage growth at sequential time-points without conducting a tissue biopsy, a procedure that’s detrimental even when taking just a tiny amount of cartilage.

Host-Margot Kern: In the trial 84% of the defect was filled with new cartilage in patients who received the gel/adhesive combo compared to just 64% in patients who received microfracture alone. And this new cartilage closely resembled the patient’s native cartilage at six months as verified by MRI. Additionally, patients who received the gel/adhesive combo reported a decrease in pain at six months post-surgery. 

Host-Margot Kern: Hunziker says the study is exciting because it combines advancements in the fields of bioimaging and bioengineering to solve a long-standing problem in the field of cartilage repair.

Hunziker: Dr. Elisseeff’s lab may have found that elusive holy grail which is tissue integration. But it’s also important to note the significance of the novel MRI techniques that were used here to evaluate the new cartilage non-invasively.  It was really a critical component to the study, because if we didn’t have it, we wouldn’t have an objective method for determining whether Elisseeff’s complex strategy was really working.

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