A regenerative solution for spinal fusions

Example of a bilateral spinal fusion (ceramic applied to the left side)

Since the first use of autologous bone graft >100 years ago, surgeons have been looking for an alternative, because bone graft harvesting poses extra harm to the patient. Numerous alternatives have been used, including animal bone, bamboo, polymers and many types of ceramic. However, none of these matched autologous bone.

Since 2000, the Department of Orthopaedic Surgery of UMC Utrecht heavily invested in regenerative bone research. Initially the focus lied on cell-based strategies: the combination of stem cells with a carrier, the so called scaffold. Unfortunately, this strategy did not lead to any success as virtually all cells die soon after implantation. Instead, the researchers found out what scaffold characteristics are needed to regenerate bone without external cells. Based on this new knowledge, a highly sophisticated stand-alone bioactive ceramic was developed with the unique ability to induce bone at locations where bone normally does not grow.

Illustration of the intra-patient controlled study design (based on randomization, ceramic was applied to one side of the spine, whereas autologous bone graft was applied to the contralateral side)

In 2013, the research group led by Dr. Moyo Kruyt initiated the first-in-man randomized controlled trial to evaluate the innovative ceramic as an alternative for autologous bone for spinal fusion. Posterior spinal fusion poses the largest demand for autologous bone. In the Netherlands alone, thousands of fusions are done each year. The research group employed a unique intra-patient design, which means that each patient received both grafts and served as their own control. The major advantage of this design is the elimination of inter-patient variability and its numerous confounders. 100 patients were included to study non-inferiority of the bioactive ceramic after 1 year, based on CT-scans.

After 3 years, all patients were operated in this multicenter trial. Two years of follow-up was completed in 2018. The primary results showed exactly what they hoped for: the bioactive ceramic was as good as autologous bone to generate a spinal fusion. The findings by first author Mechteld Lehr and colleagues were recently accepted for publication in the American journal Spine. This is a milestone after >20 years of regenerative bone research and has enormous implications for future bone regeneration. The next aim is to outperform autologous bone graft, which may be possible by enhancing the regenerative process of the ceramics; for example with inflammatory stimuli.

Publications

Lehr M, Oner C, Delawi D, et al. Efficacy of a Standalone Microporous Ceramic vs. Autograft in Instrumented Posterolateral Spinal Fusion; a Multicenter, Randomized, Intra-patient Controlled, Non-inferiority Trial [published online ahead of print, 2020 Feb 19]. Spine (Phila Pa 1976). 2020;10.1097/BRS.0000000000003440. doi:10.1097/BRS.0000000000003440

Lehr AM, Oner FC, Delawi D, et al. Increasing Fusion Rate Between 1 and 2 Years After Instrumented Posterolateral Spinal Fusion and the Role of Bone Grafting [published online ahead of print, 2020 May 25]. Spine (Phila Pa 1976). 2020;10.1097/BRS.0000000000003558. doi:10.1097/BRS.0000000000003558