Clinical Research // Regenerative Therapies

Alejandro Almarza, PhD

Researching Regenerative Therapies

Already pioneers of regenerative therapies for temporomandibular joint (TMJ) degeneration, Alejandro Almarza, PhD, and his lab are shifting their research focus to developing novel technologies to repair the articular surface of the condyle, a bone that enables mandibular joint movement.

Almarza is an associate professor of oral and craniofacial sciences at the University of Pittsburgh School of Dental Medicine, with secondary appointments in the Department of Bioengineering at the Swanson School of Engineering and the McGowan Institute for Regenerative Medicine. His lab’s research focuses on regenerative therapies for the TMJ disc using extracellular matrix scaffolds.

The TMJ is the structure that connects the jawbone to the skull and functions similarly to a sliding hinge, which enables mandibular functions like chewing. TMJ degeneration can lead to bone-on-bone rubbing and chronic pain for patients with temporomandibular joint disorders (TMD). Currently, severe cases of TMD require autografts or alloplastic implants to relieve the chronic pain experienced by those suffering. However, secondary procedures are often necessary, as there is no permanent treatment.

“We were the first ones who showed that robust healing can occur in the TMJ, and our materials regenerate into native-like tissue in almost every aspect,” said Almarza. That native-like tissue arises as cells are recruited to the implantation site and rebuild the tissue’s original structure on the extracellular matrix scaffold. “The functional properties are on par with the original tissue,” Almarza noted.

Almarza’s research focus shifted after a collaboration with his colleague Juan Taboas, PhD, MS, associate professor, Department of Oral and Craniofacial Sciences, School of Dental Medicine, in which the Almarza lab used Taboas’ novel polymers to guide stem cell differentiation for both cartilage and bone regeneration. “One of the best things about the University of Pittsburgh is a collaborative environment,” he said.

Their work led Almarza to question why certain patients need these therapies and whether it’s possible to sense damage to these mandibular structures. And so, Almarza’s lab began investigating how the nerve endings in joints detect pain in diseased states, like osteoarthritis or TMJ degeneration, and the effect of sex and age on sensitivity.

Almarza’s team is currently beginning clinical trials to isolate tissues from patients undergoing TMJ surgery to correlate findings from their splint-induced malocclusion “bad bite” animal model of TMD pain with human disease pathology. He explained that the lab plans to take this trial further by analyzing patient clinical data, patient histories and quantitative sensory testing. These tests will probe how much pain patients feel in their pain points compared to a non-pain point to correlate those measurements for the first time.

Almarza regularly works with the TMJ Association, a patient advocacy group, and the U.S. Food and Drug Administration (FDA) and is even planning a patient roundtable discussion in fall 2023 so the FDA can listen to patients discuss their needs.

Collaborations like these are critical to the effective clinical translation of Almarza’s bench research, especially regarding TMJ devices, which are regulated as Class III medical devices. This regulation was instated in response to unregulated research in the 1970s and 1980s. The extent of this unregulated research was so severe that the FDA banned all TMJ devices for nearly two decades. “Having the highest-level of regulation with one of the smallest markets has really hampered innovation in terms of translating technologies from the bench to the clinic,” said Almarza.

With support from the NIH Helping to End Addiction Long-term (HEAL) Initiative Restoring Joint Health and Function to Reduce Pain Consortium, Almarza communicates regularly with the FDA to provide clear metrics on how their device works. Through this partnership, conducting thorough trials in animal models and more, he hopes to help the FDA understand the safety of their technologies so he can begin introducing them into the market. “The HEAL initiative is all about building consortiums and teams so that we’re not in one isolated environment, and we’re going to try to change the research culture,” he said.

Almarza emphasized the importance of collaboration both within the University and within the larger scientific community. “We’re going to try to be a lot more open and collaborative, not just within the institution, but across universities,” said Almarza. Through these collaborations, Almarza and his team continue to listen to patient needs as they work to introduce safe, innovative technologies into the marketplace.

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