Rice University’s Brendan Watson, a graduate student in the laboratory of Dr. Antonios Mikos from the Departments of Bioengineering and Chemical and Biomolecular Engineering, published a study in Biomacromolecules that describes what can be considered a “smart” hydrogel system to be applied to bone tissue engineering, or reconstruction.
Watson’s hydrogel is a thermogelling polymer, meaning that liquid monomers at room temperature polymerize into a gelatinous network upon heating. In this specific case, Watson’s hydrogel forms upon injection into a patient when the gel is warmed to body temperature. If the hydrogel is injected into a bone defect, the gel fills and stabilizes the space until degradation and natural tissue ingrowth occur.
But this is no ordinary thermogelling polymer, as explained by Dr. Mikos in a news release: “This study describes the development of a novel thermogelling hydrogel for stem cell delivery that can be injected into skeletal defects to induce bone regeneration and that can be degraded and eliminated from the body as new bone tissue forms and matures.”
A patient’s own stem cells can be encapsulated in the hydrogel as it forms and provide better healing, according to Watson, who demonstrated the gelation process in a video.
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Another unique aspect of the system is its solution to a problem common to thermogelling polymers. Most thermogelling polymers collapse and expel water in a process known as syneresis, which defeats the hydrogel’s purpose of filling the bone defect. “If the transition gelation temperature is one or two degrees below body temperature, these polymers slowly start to expel water and shrink down until they’re one-half or one-third the size. Then the defect-filling goal is no longer accomplished,” said Watson. The solution is a set of chemically cross-linkable methacrylate groups that stabilize the gel.
Stability of the gel is important in order for cells to proliferate and build tissue, but over time the material needs to be removed and replaced by tissue. This is where another unique characteristic of the hydrogel comes into play. Buried within the chemical cross-links are degradable phosphate ester bonds, which break down to yield macromers that are soluble at physiologic temperature and minimally cytotoxic. “[The bonds] can be degraded by catalysts–in particular, alkaline phosphatase–that are naturally produced by bone tissue,” explained Watson. “The catalysts are naturally present in your body at all times, in low levels. But in areas of newly formed bone, they actually get to much higher levels. So what we get is a semismart material for bone-tissue engineering. As new bone is formed, the gel should degrade more quickly in that area to allow even more space for bone to form.” In addition to degradation dictated by the body, the hydrogel can be synthetically designed to degrade at a rate to match the rate of bone growth, but Watson says, “Optimizing the degradation kinetics is nontrivial and may be better suited for a biotech company. We focus more on the performance of the hydrogels and the underlying molecular mechanisms.”
Watson received help from his colleagues and co-authors, who included Dr. Paul Engel, chair of the Department of Chemistry, and Dr. F. Kurtis Kasper, a senior faculty fellow in bioengineering who received a grant for bone tissue engineering research last year. “I came up with the idea a few years ago, but it’s finally all come together,” concluded Watson.