We’ve all signed a child’s colorful cast on their broken arm, gotten a call to inform us an elderly relative fell and broke a hip, or been laid up with back spasms ourselves. Maybe you’ve had a knee replacement or dealt with joint pain from years of athletic activity. It’s practically inescapable — 1 in 2 American adults suffers from a musculoskeletal disorder or injury such as arthritis, chronic back pain, fractures, or osteoporosis, according to 2016 data from the United States Bone and Joint Initiative (USBJI).
This is compounded by the fact that the U.S. has a rapidly aging population and, as people age, they lose bone density and the risks increase. Experts say the incidence of and costs to treat such issues are in danger of spiraling out of control.
But researchers at UConn and UConn Health are using a host of materials and technologies — from stem cells to spider-spun silk fibers to hydrogel to ultrasound waves — to strengthen bones and joints and accelerate recovery from musculoskeletal diseases and injuries.
“Musculoskeletal injuries are among the most common reasons to see a doctor. If we can take care of those faster and more effectively, patients can get back to their activities and work faster.”
“Musculoskeletal injuries are among the most common reasons to see a doctor. If we can take care of those faster and more effectively, patients can get back to their activities and work faster, which helps everybody,” says Dr. Augustus D. Mazzocca, director of the UConn Musculoskeletal Institute (MSI) and chair of the Department of Orthopaedic Surgery at UConn Health.
“There’s the economic impact of having people out of work, and the emotional problems of people who lose mobility and are isolated,” he says. “We’re trying to bring you back into society and get you back to what you like to do.”
To that end, UConn Health doctors also are developing ways to get you home faster after any musculoskeletal procedure, including spearheading same-day joint replacements.
Faster, Safer Recovery
UConn Health hip and knee replacement patients don’t have to wait for our clinical innovations to come to market. They can benefit from new approaches to the surgeries right now — and “right now” might also describe when they can go home post-op.
“Nearly 100 percent of my patients go home within 24 hours, and some now the same day,” says Dr. Mo Halawi, a new UConn Health orthopaedic surgeon who specializes in joint reconstruction and is spearheading an effort to minimize the time these patients spend in the hospital recuperating.
“The criteria for discharge are identical whether a patient leaves on the day of surgery or several days later. But with minimally invasive techniques, regional anesthesia, blood-conserving strategies, opioid-sparing analgesia, and immediate mobilization, patients are now achieving recovery milestones a lot quicker than before,” he says.
According to Halawi, the ideal candidate for same-day total joint replacement is one who is independent, motivated, has a good support system, and has no major risk factors for surgical complications. Much of the work is done in advance to optimize patients’ health and prepare them for surgery, allowing for the
After surgery, Halawi takes a less-is-more approach. Patients get on their feet right away and have no IV medications, drains, catheters, dressing changes, braces, or laboratory tests. Very rarely do his patients get discharged to nursing homes or rehabilitation facilities. Studies have shown that “patients recover better and have fewer complications in the comfort
of their homes,” he says.
“Hip- and knee-replacement surgery is constantly evolving, and we need to always deliver safe, effective, efficient, and evidence-based medicine to our patients. Soon, more surgeons and patients will realize that long hospital stays and recovery times are outdated,” Halawi says.
Though it is in the very early stages of development, UConn Health tissue engineer Syam Nukavarapu and his team have created a hybrid hydrogel system that they hope is the first step toward forming a hypertrophic cartilage template with all the right ingredients to initiate bone tissue formation, vascularization, remodeling, and ultimately the establishment of functional bone marrow to repair long bone defects.
How the more than 200 bones in an adult human skeleton form and how they are repaired if injured varies and has posed a challenge for many researchers in the field of regenerative medicine.
The cartilage template Nukavarapu and his team created appears to overcome hurdles that make it difficult for regenerative scientists to help the body’s long bones regenerate.
Two processes involved with human skeletal development help all the bones in our body form and grow. These processes are called intramembranous and endochondral ossification: IO and EO respectively.
While they are both critical, IO is the process responsible for the formation of flat bones, and EO is the process that forms long bones like femurs and humeri.
For both processes, generic mesenchymal stem cells (MSCs) are needed to trigger the growth of new bone. Despite this similarity, IO is significantly easier to re-create in the lab since MSCs can directly differentiate, or become specialized, into bone-forming cells without any additional steps.
However, this relative simplicity comes with limitations. To circumvent the issues associated with IO, Nukavarapu’s team set out to develop an engineered extracellular matrix that uses hydrogels to guide and support the formation of bone through EO.
“Thus far, very few studies have been focused on matrix designs for endochondral ossification to regenerate and repair long bone,” says Nukavarapu, who holds joint appointments in the departments of Biomedical Engineering and Materials Science and Engineering. “By developing a hybrid hydrogel combination, we were able to form an engineered extracellular matrix that could support cartilage-template formation.”
Nukavarapu’s team’s findings could be the first step to initiating the proper healing of long bones with biomedical help.
Using the Wisdom of Spider Webs
When someone breaks a load-bearing bone — the femur, for instance — doctors might install a metal plate to support the bone as it fuses and heals. But the metal can cause inflammation and irritation, and since metals are very stiff, the new bone may grow back weaker and more vulnerable to fracture.
UConn materials scientist and biomedical engineer Mei Wei and her team have developed an alternative to metal: a composite made with silk fibroin, a protein found in the silk fibers spun by spiders and moths and a common component in medical sutures and tissue engineering because of its strength and biodegradability.
Wei’s study found that the high-performance biodegradable composite showed strength and flexibility characteristics that are among the highest ever recorded for similar bioresorbable materials.
Working with UConn mechanical engineer Dianyun Zhang, Wei’s lab created a mix of silk and polylactic acid fibers coated in bioceramic particles. The new composite lasts about a year — large, adult leg bones can take many months to heal — and then starts to degrade. No surgery is required for removal.
Tissue engineer Syam Nukavarapu (left) examines a specimen of his hybrid hydrogel in his UConn Health lab.
Capturing the Power of Ultrasound
In the Department of Orthopaedic Surgery and the Institute for Regenerative Engineering at the UConn School of Medicine, researchers Yusuf Khan, Bryan Huey, and Lakshmi Nair are studying the combined power of gel-encapsulated bone cells and ultrasound waves to help fractured bones heal.
Physical force has been shown to stimulate bone cell regeneration for full healing, but immobilizing the fracture with a cast doesn’t allow for any movement. Khan believes that adding cells to the fracture site early on, and then directing a transdermal physical force toward the cells via low-intensity ultrasound, could accelerate fracture repair. In cases where a fracture can’t heal on its own, the therapy could provide the necessary stimulus to complete the healing process.
The team’s lab has already demonstrated the successful placement of bone cell hydrogels in mice and is working with the Department of Materials Science and Engineering to optimize the gel capsules for human use.
Harnessing Stem and Amniotic Cell Strength
Dr. Cato T. Laurencin, the Albert and Wilda Van Dusen Distinguished Professor of Orthopaedic Surgery and the director of the Institute for Regenerative Engineering at UConn Health, is developing clinical therapies to treat — and potentially reverse the effects of — osteoarthritis using human amniotic tissue, stem cells, and new combinations of the two.
An estimated 20 percent of Americans suffer from osteoarthritis, the most common degenerative joint disease and the leading cause of disability worldwide. Although current surgical and non-surgical therapies can provide some relief, none treat the root cause of the disease.
Stem cells have been proven to reduce pain and improve function in osteoarthritis patients. New studies suggest that the use of stem cells may heal cartilage, but results vary. Thanks to the host of powerful cytokines contained in amniotic tissue, many of which have been shown to decrease inflammation, Laurencin believes human amniotic tissue may overcome the limitations of current stem cell therapies, providing an ideal delivery system with added benefits.
“Soon, more surgeons and patients will realize that long hospital stays and recovery times are outdated.”
In its initial studies, Laurencin’s team has found its amnion-based delivery system can support stem cell survival, growth, and proliferation, and that the combination of amnion matrices and stem cells have immunosuppressive and anti-inflammatory effects on knee tissue cells.
“We believe amniotic tissue growth factors help drive human development and regeneration,” says Laurencin. “We are hopeful that harnessing this powerful new cell combination will help us further advance regenerative engineering for patients, especially those with arthritis or sports injuries, who want to avoid steroid treatments or are interested in next-generation therapies.”
Although it is not yet covered by insurance, amnion tissue treatment is available now to Laurencin’s patients. Laurencin’s team hopes to make the combination amnion¬stem cell therapy available within the next three years.
From the advanced research that’s changing the care of the future to the clinical changes happening now, Musculoskeletal Institute head Mazzocca says the Institute is uniquely positioned to provide the best possible care to patients.
“We try to take all the clinical people that treat musculoskeletal disease — rheumatology, osteoporosis, comprehensive spine, orthopaedics — and put it in one place, and combine them with all the researchers so they can cross-pollinate and make care better for the people of the state of Connecticut,” he says. “And there’s nobody else in the state of Connecticut that does what we do.”
Jessica McBride, Colin Poitras, and Lauren Woods contributed to this story.