The Role of Biologics in Minimally Invasive Spine Surgery

55 The Role of Biologics in Minimally Invasive Spine Surgery

Howard An

Summary

In performing spinal fusion in MIS, proper selection of bone grafts and bone graft substitutes is paramount in achieving solid fusion. Proper surgical indications, meticulous preparation of the host endplates, and appropriate selection of interbody cage and biologics will lead to good surgical outcomes with fewer complications.

Keywords: biologics intervertebral disc repair and regeneration bone grafts and bone graft substitutes

55.1 Introduction

The narrower access corridors used in minimally invasive (MI) spine surgery has necessitated several technological advances. Although advances in instrumentation and technique have been critical, the success of MI spine surgery would be unthinkable without advances in biologic tools. On the one hand, technologies like novel bone graft extenders, bone morphogenetic protein (BMP), and bioactive materials are all critical to the success of modern MI techniques. On the other hand, bioregenerative interventions to treat degenerative disc disease have also been used with initially promising results. This chapter provides a brief overview of biologics in MI spine surgery and discusses exciting technologies that are currently in development.

55.2 Biologics for Spinal Arthrodesis

Spinal biologics enhance bone formation via osteoinductive, osteoconductive, osteogenic, or a combination of the three mechanisms.1^,²^,³ Osteoinductive materials “induce” pluripotent stem cells to differentiate into osteoblastic, bone-forming phenotypes. Osteoconductive materials provide a scaffold for new bone formation. Osteogenesis refers to continued production of bone by pre-existing bone-forming cells.

Because MI approaches rely on narrow access corridors, surgeons often have access to a limited quantity of local autograft bone. Despite this fact, good results have been described when local bone shavings, excised facet bone, and iliac crest autograft⁴^,⁵^,⁶ are used in MI transforaminal lumbar interbody fusions. Autograft bone remains a desirable graft choice when available because it is osteoinductive, osteoconductive, and osteogenic.

Allograft bone, in contrast, is primarily osteoconductive with only weak osteoinductive effects.³ For this reason allograft bone is typically used in conjunction with osteoinductive agents (e.g., BMP).⁷^,⁸ Corticocancellous allografts provide mechanical support in addition to osteoconduction and are commonly used in the cervical spine.⁹^,¹⁰

In addition to allograft bone, synthetic osteoconductive scaffolds and osteoinductive materials may be utilized. These products are referred to as bone graft extenders and include demineralized bone matrix (DBM), bone ceramics, and rhBMP. DBM is allograft bone that has been demineralized using a chemical process. DBM consists of an osteoconductive scaffold that also contains bone-forming proteins (e.g., BMP) to provide an osteoinductive effect, albeit weak due to low concentrations of BMPs in the products. Bone ceramics are comprised of a mix of hydroxyapatite (HA) and tricalcium phosphate (TCP). Their structure provides an osteoconductive scaffold for bone growth.³^,¹¹^,¹² BMPs are proteins within the transforming growth factor beta (TGF-β) superfamily. They induce the differentiation of pluripotent mesenchymal stem cells toward osteogenic and chondrogenic phenotypes by stimulating angiogenesis and alkaline phosphatase activity.¹³ Recombinant human BMP in the supraphysiologic concentration is widely utilized in MI surgeries via the anterior, lateral, or posterior approaches to assist with interbody fusion, but caution should be taken to avoid complications such as inflammation of surrounding structures, including nerves and ectopic ossification.⁶^,¹⁴

55.2.1 Biomaterials in Spine Surgery

Using lessons learned from total joint arthroplasty, there have been several recent advances in spinal biomaterials to improve bony on-growth at the bone–implant interface. Traditional polyether ether ketone (PEEK) cages are widely used because of their radiolucency and desirable biomechanical properties. Although excellent results have been reported, there are concerns about the halo formation at the PEEK–bone interface.¹⁵ Several surface modifications to PEEK have been proposed to improve osseointegration. These include the development of porous PEEK and surface treatments with titanium, HA, and various bone ceramics.¹⁶^,¹⁷^,¹⁸^,¹⁹ Although clinical data is limited,²⁰ there is promising animal and biomechanical data supporting these technologies. Novel ceramic materials such as silicon nitride with favorable biomechanical, osseointegrative, and antimicrobial properties have also been developed recently. Clinical trials studying this new material are currently underway.²¹^,²²

55.2.2 Biologic Approaches to Treating Degenerative Disc Disease

Given the immense burden of degenerative disc disease, strategies to repair and regenerate degenerative intervertebral discs (IVD) are an active area of investigation that are likely to represent the “next wave” in spine surgery. Strategies to repair discs include: injection of proteins (e.g., BMP7²³^,²⁴), injection of growth factors (e.g., platelet-rich plasma, PRP²⁵^,²⁶), gene therapy to reduce the expression of degradative molecules,²⁷^,²⁸^,²⁹ annular repair,³⁰ cell-based therapies,³¹^,³² and total disc transplantation³³^,³⁴ (Fig. 55.1). There is strong in vitro and animal model data to support these strategies. Injection of BMP7 in a rabbit model of IVD degeneration, for example, has been shown to restore disc height and restore the biomechanical properties of degenerated intervertebral discs.²³^,²⁴ Similarly, injection of autologous or allogeneic chondrocytes into the IVD results in the production of disc matrix and decreased signs of degeneration on magnetic resonance imaging (MRI).³² Mesenchymal stem cells harvested from bone marrow or adipose tissue can differentiate into bone, cartilage, and other connective tissue. Implantation of these cells into the disc has also been shown to help regenerate disc matrix.³¹ Although existing clinical data is limited, there are several clinical trials underway to determine the efficacy of these approaches to slow and potentially reverse disc degeneration.