Research to Develop Non-Invasive Spine Fusion

Anna-Maria and Stephen Kellen Physician-Scientist Career Development Award Program- Part II

Research to Develop Non-Invasive Spine Fusion

We will post a series of blogs which will discuss specific research projects that are being conducted in part to the Anna-Maria and Stephen Kellen Physician-Scientist Development Award Program. In our second installment, Dr. Matthew E. Cunningham discusses his research on the development of non-invasive spine fusion. 

Spine and scoliosis surgeons attempt to treat their patient’s conditions and ailments with non-operative options at first, including physical therapy, medicines taken orally (non-steroidal drugs among others), and specialized injections (epidural steroid injections, trigger points, and intra-articularly to the facets and sacro-iliac joints). But when clinical symptoms from end-stage arthritis, instability or spine deformity do not respond to non-operative measures, patients frequently need to undergo fusion of the spinal vertebral bones. Spine fusions can greatly improve or eliminate clinical pain symptoms, but the surgeries are relatively extensive and can have complication rates up to as high as 60% in some patient demographic populations. In an effort to minimize complications, hasten postoperative illness, and return patients to activities of daily living more quickly, I have been researching a method whereby a patient could obtain a solid spinal fusion after undergoing only an injection. Theoretically, this technique could eliminate postoperative procedure-related pain and requirement for hospitalization,. In addition, patients would not be at risk for intraoperative blood loss necessitating transfusion, wound infection, or other iatrogenic sequelae.

The spine is a repetitive series of hard bones (vertebrae) that support the structure of the spinal column, and soft-tissue discs between the vertebrae that allows spinal motion. There are also a collection of muscles that attach to the vertebral and other bones (such as the pelvis, ribs and shoulders) that support the spine in 3-dimensions. My research has concentrated on the disc tissue, in that it is a contained locale between 2 vertebral bones, which if converted from soft-tissue disc to bone, would allow the fusion of those 2 vertebral bones into a single one. The disc is comprised of 2 tissues: an inner jelly-like Nucleus Pulposus, and an outer ligament-like Annulus Fibrosus (AF). The disc is largely devoid of a blood supply, and gets its nutrition through diffusion from the peripheral AF capillaries, and those present in vertebrae juxtaposed proximally and distally to the disc. The NP tissue also appears to have an inherent homeostasis mechanism to prevent bone formation within the disc. Without a sufficient blood supply in the disc tissue, and with a tissue that apparently thwarts bone production, we expected that the research goal for developing a treatment to be injected into the NP space to make the disc turn into bone would be challenging. Delivery of genes (specific bits of DNA encoding proteins of interest) to alter the environment within the disc was chosen as a powerful method thorough which we might be able to achieve the goal. Initially, bone growth factors (bone morphogenetic proteins or BMPs) were utilized, and impressive amounts of bone were produced outside of the disc space that ultimately led to spine fusions in an animal model. Later study allowed us to discover a small molecule that made the NP tissue permissive to blood vessel ingrowth, a potentially big step forward towards making the disc more hospitable to bone growth.

The Kellen Physician-Scientist Center Development Award has enabled me to continue the quest towards injection-based non-invasive spine fusion. The grant support helps to fund a full time technician and PhD-level graduate student in my lab who complete the day-to-day work that has enabled us to make further discoveries, including delivery of 2 specific genes that render the NP cells permissive to generate calcium crystals within the NP disc tissue. Full description of the molecular mechanisms involved in this gene-mediated “reprogramming” of the NP cells is underway, and we are very excited about what this might mean for production of “real bone” within the disc space. I am very appreciative of the support provided by both Maria Kellen-French and HSS to provide the opportunity to continue by basic and translational research, and I remain confident that we will keep making progress towards, and eventually achieve the goal of percutaneous spine fusion.

Matthew E Cunningham MD PhD is an orthopedic surgeon at HSS, specializing in Pediatric and Adult, Spine and Scoliosis surgery. Dr. Cunningham’s interests include minimally invasive and open surgery for spine deformity and degenerative conditions. He currently is the Interim Chief of the Scoliosis Service, Director of the John Cobb Scoliosis Fellowship, Principal Investigator of the Molecular and Cellular Spine Research Laboratory at HSS, and acts as a reviewer for Clinical Orthopedics & Related Research, Hospital for Special Surgery Journal, Journal of Orthopedic Research, Arthritis Research & Therapy Journal, Scoliosis Journal, Biochemistry Journal, American Academy for Laboratory Animal Science Journal, and Journal of Biomechanics.

The information provided in this blog by HSS and our affiliated physicians is for general informational and educational purposes, and should not be considered medical advice for any individual problem you may have. This information is not a substitute for the professional judgment of a qualified health care provider who is familiar with the unique facts about your condition and medical history. You should always consult your health care provider prior to starting any new treatment, or terminating or changing any ongoing treatment. Every post on this blog is the opinion of the author and may not reflect the official position of HSS. Please contact us if we can be helpful in answering any questions or to arrange for a visit or consult.


  1. I have a failed c56 and c67 spinal fusion. I have seen two doctors that only agree on the fact I need another surgery. One wants to redo it from the front and the other wants to go in from the back. I’m so confused can you offer me any help or advice.

    1. Hi Keri, thank you for reaching out. Dr. Han Jo Kim, Orthopedic Surgeon, says: “If the posterior approach was chosen because the patient has developed a pseudarthrosis, then I believe this is a better approach than performing a revision operation from the anterior approach.” It would be best for you to seek an in-person consultation with a physician so that they can determine the best course of treatment. If you wish to receive care at HSS, please contact our Physician Referral Service at 877-606-1555 for further assistance.

  2. How can simply fusing the vertebrae correct scoliosis? That is probably not what this is indicated to do. I am 49 with double 50 degree curves, fused L4 to sacrum for pain elimination, spinal stenosis, etc. I am afraid that if I don”t correct the scoliosis now, surgically, I will face osteoporosis with aging and surgery will no longer be an option. It took a full 2 years to get over the last surgery. I have tried therapy, to no avail. My scoliosis looks worse and pain is almost constant. Is there hope?

    1. Hi Lisa, thank you for reaching out. Dr. Matthew Cunningham, Orthopedic Surgeon, says: “The proposed injection would only stabilize the spine to prevent further spine degeneration and progression of spine deformity at the segments fused. In the vast majority of cases, it is not the scoliosis that hurts, it is the degeneration and arthritis that develops within the curves that causes pain symptoms. To your point, however, if the scoliosis was relatively flexible, a brace could be used to push the spine in a relatively straighter position and hold it there while the injection-based fusion happened. Perhaps the easiest to explain application of the injection technique for scoliosis would be in a pediatric population where the behavior of the scoliosis could be predicted and severe curves prevented by intervening early where curves are still small; pediatric spine deformity that predictably becomes severe enough to require surgery are kids with scoliosis that have muscular dystrophy and multiple other syndromes, or children with adolescent idiopathic scoliosis and genetic testing suggestive of high risk for progression.

      There are hundreds of investigators across the USA, and thousands around the world, working to optimally treat and manage spine deformity. Today, the best management might likely be for further surgery to include the painful segments above the fusion you have already had. However, before any surgery was contemplated, I’d seriously consider treatment with a Pain Management or Physiatry specialist to see if there were non-surgical treatments that would be able to manage the pain that you experience. Sometimes injections can help for leg pain (epidural steroid injections), or back pain (sacroiliac joint injections, facet injections, disc-directed therapies) associated with scoliosis. If the injections are helpful in controlling symptoms, there may also be options to get more durable relief of symptoms with radio-frequency ablations (facets, SI joints, etc.). In the meantime, feel assured that researchers around the world are looking for increasingly improved solutions to your problems.”

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