Regenerative treatment strategies in spinal surgery

Abstract

Intervertebral disc degeneration is considered a major source of low back pain. Recent advances in regenerative medicine have led to promising new approaches for the biological treatment of disc degeneration. Treatment modalities include the administration of growth factors, the application of autologous or allogenic cells, gene therapy, in situ therapy and the introduction of biomaterials or a combination thereof. Promising experimental results in vitro and in animal studies support the potential feasibility of these treatment modalities in clinical studies. We will review the current literature on regenerative treatment strategies and discuss potential drawbacks as well as opportunities in translating current knowledge into clinical practice. Major obstacles to regenerative treatment strategies might be insufficient nutritional supply, pain mediating factors and functionally impaired donor cells. Therefore, for clinical application, patient selection will be essential. Molecular, cellular and radiological diagnostic tools to evaluate the eligibility of patients for particular treatment strategies need to be developed. In spinal surgery, two approaches are conceivable. Patients operated on lumbar disc herniations often develop back pain due to disc degeneration months to years after surgery. Here, additional regenerative interventions would have a preventive intention, whereas interventions for painful degenerative disc disease as an alternative to spinal fusion or disc arthroplasty would be a curative approach.

Rheological characterization of the nucleus pulposus and dense collagen scaffolds intended for functional replacement

“…This gave researchers the impetus to develop regenerative strategies that deal with the damaged intervertebral disc, especially the nucleus pulposus (NP). 2 Scaffolds for NP replacement are enriched with stem cells, growth factors, and/or additional molecules in order to promote and utilize the regenerative potential of the human body. 3 Under physiological conditions, cells within a scaffold are able to synthesize and secrete their own extracellular matrix (ECM).…”

Methods to monitor distribution and metabolic activity of mesenchymal stem cells following in vivo injection into nucleotomized porcine intervertebral discs

“…In the in vivo model used in this study, injury to the AF and partial nucleotomy is carried out before the cell transfer to generate conditions which mimic the human situation, where after discectomy the protruded nucleus pulposus is removed. Current discectomy procedures in humans, are presently not directed to regenerate the damaged intervertebral disc (IVD) and, thus, are only symptomatic [13,16,26]. One important novum in our study was the separate analysis of implant retention and anabolic activity of transferred cells in an in vivo model, which offers for the first time the possibility to follow up tissue engineered bioconstructs after transplantation in vivo.…”

“…Although during the last years, increasing knowledge and technical advancements in the field of tissue engineering has resulted in numerous promising strategies to repair, replace, or regenerate the herniated nucleus pulposus [26,50], none of these advancements has yet resulted in a clinically proven effective therapy. One of the major limitations is the lack of effective strategies that deal with the damaged annulus fibrosus [56].…”

“…Current discectomy procedures, however, are not directed to treat the damaged intervertebral disc (IVD) and may even further aggravate existing damage [13,16,26]. It is therefore not surprising that successful neurological decompression is often followed by periods of persisting low back pain, severely affecting the quality of life [6,7,26].…”

In vitro and in silico investigations of disc nucleus replacement

“…During the last decade, better understanding of the intervertebral disc function and technical advancements in the field of tissue engineering have resulted in numerous strategies to replace or regenerate the nucleus pulposus for the treatment of low back pain in the early stages of disc degeneration [5,6]. While hydrogels are considered as one of the most promising solutions [7], nevertheless no procedure has yet been recognized as a clinically proven effective therapy.…”