Breakthrough Research in Synthetic Mesh

In Vivo study of patented collagen biomaterial shows promise for pelvic floor reconstruction

Innovations in Urology - Winter 2019

Through collaborative translational research at University Hospitals Cleveland Medical Center and Case Western Reserve University, a team of physicians and engineers has developed a novel woven collagen mesh material for potential use in mid-urethral sling (MUS) surgeries.

Over the past decade, exploration of effective biomaterials for treatment of stress urinary incontinence (SUI) and pelvic floor reconstruction has gained attention in response to concerns about synthetic mesh complications.

“The quest for synthetic mesh alternatives aims to address an unmet need for an ideal implantable material,” says Adonis Hijaz, MD, Director, Female Pelvic Surgery at UH Cleveland Medical Center and Vice Chair of Academics and Research for the UH Urology Institute. “Our overarching mission is to help our patient population and give women a safe, durable repair for incontinence or prolapse.”

Adonis Hijaz, MD

Dr. Hijaz is developing the patented collagen-based MUS prototype in collaboration with researchers including Ozan Akkus, PhD, a Leonard Case Jr. Professor of Engineering at Case Western Reserve University. Dr. Akkus and his team invented a novel mechanism to convert a collagen solution into threads of electrochemically aligned collagen (ELAC) that can be woven into a macroporous mesh. Funding through a National Institutes of Health (NIH) R21 grant is supporting further investigation of the material for safety and efficacy. 

To date, functional testing in both small and large animal models has shown exciting promise for the innovative engineered tissue. This past year, the team published their early findings in the Journal of Biomedical Materials Research Part B: Applied Biomaterials.¹

In the study, mesh samples of ELAC were implanted in a subcutaneous rat model and explanted at various time intervals to evaluate biocompatibility (tested at two weeks, two months and five months) and mechanical properties (baseline, two months and five months) to determine suitability for use as a MUS for management of SUI. Implants of porcine dermal (Xenmatrix) and monofilament polypropylene (Prolene) meshes were also included for comparison. In total, 25 animals were implanted for this study, with 15 monitored for biocompatibility and 10 monitored for mechanical properties at the predetermined endpoints.

The results were promising. “We found that the product exhibited both the tensile strength of the synthetic sling and the stiffness of native tissue,” Dr. Hijaz says. “Additionally, we saw no significant acute or chronic inflammation. What was particularly interesting was evidence of replacement of the collagen fibers we originally implanted with new, well-aligned collagen that the hosts deposited into the material.” 

Dr. Hijaz explains that when biological material like collagen is implanted, the fibers are assumed to disintegrate over time. Researchers were encouraged by the cellularization and integration of host tissue within the surgically-placed mesh samples.

FUNDING FROM OHIO THIRD FRONTIER 

To pursue further study of the collagen mesh, the research team was awarded a grant through the UH Ventures Ohio Third Frontier Technology Validation and Start-up Fund (TVSF). The fund supports higher education and nonprofit research institutions in their efforts to develop and commercialize emerging technologies. 

Grant funding has enabled study of the collagen mesh in large animal models. 

“We recently concluded a six-month experiment of sheep implanted with our human-sized collagen sling,” Dr. Hijaz says. “Our mechanical and histological analysis of the extracted material confirmed what we saw in our small animal models, which was a positive outcome. This spring, we will harvest a second set of sheep that we have survived for a year.”

BUSINESS DEVELOPMENT UNDERWAY

While UH researchers work through the necessary logistical phases prior to clinical availability in humans, a spin-off company, CollaMedix, Inc. was formed to address production and scalability. To fund next steps, the startup is raising capital and has applied for an NIH small business innovation research (SBIR) grant. 

“We’re optimistic,” Dr. Hijaz says. “This is an exciting breakthrough innovation in the biomaterials space. While our initial investigation is in my field of pelvic floor reconstruction, our hope is that one day this product will replace synthetic mesh material for a wide range of medical and surgical applications.”

For more information, call the UH Urology Institute at (216) 844-3009 or contact Dr. Hijaz at Adonis.Hijaz@UHhospitals.org.

REFERENCES
1. Chapin K, Khalifa A, Mbimba T, McClellan P, Anderson J, Novitsky Y, Hijaz A, Akkus O 2018. In vivo biocompatibility and time-dependent changes in mechanical properties of woven collagen meshes: A comparison to xenograft and synthetic mid-urethral sling materials. J Biomed Mater Res Part B 2018:00B:000–000.