Biomaterials and Bioactive Agents in Spinal Fusion

Abstract

Management of degenerative spine pathologies frequently leads to the need for spinal fusion (SF), where bone growth is induced toward stabilization of the interventioned spine. Autologous bone graft (ABG) remains the gold-standard inducer, whereas new bone graft substitutes attempt to achieve effective de novo bone formation and solid fusion. Limited fusion outcomes have driven motivation for more sophisticated and multidisciplinary solutions, involving new biomaterials and/or biologics, through innovative delivery platforms. The present review will analyze the most recent body of literature that is focused on new approaches for consistent bone fusion of spinal vertebrae, including the development of new biomaterials that pursue physical and chemical aptitudes; the delivery of growth factors (GF) to accelerate new bone formation; and the use of cells to improve functional bone development. Bone graft substitutes currently in clinical practice, such as demineralized bone matrix and ceramics, are still used as a starting point for the study of new bioactive agents. Polyesters such as polycaprolactone and polylactic acid arise as platforms for the development of composites, where a mineral element and cell/GF constitute the delivery system. Exciting fusion outcomes were obtained in several small and large animal models with these. On what regards bioactive agents, mesenchymal stem cells, preferentially derived from the bone marrow or adipose tissue, were studied in this context. Autologous and allogeneic approaches, as well as osteogenically differentiated cells, have been tested. These cell sources have further been genetically engineered for specific GF expression. Nevertheless, results on fusion efficacy with cells have been inconsistent. On the other hand, the delivery of GF (most commonly bone morphogenetic protein-2 [BMP-2]) has provided favorable outcomes. Complications related to burst release and dosing are still the target of research through the development of controlled release systems or alternative GF such as Nel-like molecule-1 (NELL-1), Oxysterols, or COMP-Ang1. Promising solutions with new biomaterial and GF compositions are becoming closer to the human patient, as these evidence high-fusion performance, while offering cost and safety advantages. The use of cells has not yet proved solid benefits, whereas a further understanding of cell behavior remains a challenge.

Repair of Iliac Crest Defects with a Hydroxyapatite/Collagen Composite

“…Iliac crest autograft has been the gold standard in spinal fusion surgery for a long time because of its osteogenic, osteoinductive, osteoconductive, and non-immunogenic properties [3]. In order to enhance spinal fusion and avoid the morbidity of autograft harvesting, many bone graft substitutes have been developed [2,3,16]. Currently, there are four main classes of bone graft substitute: ceramic-based synthetic grafts, allografts, recombinant human bone morphogenetic proteins, and mesenchymal stem cells.…”

“…The use of iliac crest bone graft has long been the gold standard in orthopedic surgery in general, as well as in spinal fusion, because of its superior biological and nonimmunologic properties compared with those of other materials [2,3]. The iliac crest is easy to access and can provide ample bone.…”

“…Another recognized advantage is the low cost and close to zero risk of disease transmission. However, there are disadvantages in that the bone needs to be harvested from the iliac crest; the surgical time is higher; and there is a risk of infection, hematoma, fracture, and pain [2,4]. Limited bone supply is another problem.…”

Are orthobiologics the next chapter in clinical orthopedics? A literature review

“…Used in combination with a carrier, its clinical use is mostly in spine surgery as a bone graft extender, rather than a single effective orthobiologics solution. [6,7] There are also reports on its use in ankle fusions and treatment of unicameral bone cysts in combination with autologous grafting. [8,9] Autologous bone marrow aspirate is also a classical technique used to stimulate bone growth and angiogenesis.…”

Spinal Biologics in Minimally Invasive Lumbar Surgery

“…Demineralized Bone Matrix (DBM) is a human allograft-derived bone graft first introduced in 1991 as a substitute or additive to autologous bone grafts [ 91 ]. After its procurement from human cadaveric bone, it is treated with acid that removes the mineralized portion while maintaining the collagens (mostly type I with some types IV and X), the noncollagenous proteins, and certain growth factors (GF) [ 92 ].…”